Alzheimer DiseasePhase 4DARIDOR-ALZNCT05924425
Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease
A Phase 4 study testing Daridorexant 50 mg, Polysomnography and Neuropsychological assessment in people with Alzheimer Disease and Insomnia Disorder, run by University Hospital, Montpellier at 1 site in France.
Trial summary
DARIDOR-ALZ is a phase IV clinical trial designed to evaluate both the efficacy and safety of daridorexant, a selective dual orexin receptor antagonist that blocks the actions of the orexin neuropeptides at both orexin-1 and orexin-2 receptors, in selected populations of MCI and mild-to-moderate AD patients with… Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer Disease, Insomnia Disorder, Sleep
- What is being tested?
- Daridorexant 50 mg, Polysomnography and Neuropsychological assessment
- Type of treatment
- Pill or oral medicine, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- 13 Mar 2024to 13 Mar 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age [60-85] years old
- Outpatients
- Pre-screening:
- Complaints of dissatisfaction with sleep quantity or quality, despite adequate opportunity for sleep, at least 3 nights per week and for at least 3 months, and
- Total sleep time causes clinically significant distress or impairment in daytime functioning, and
- Total sleep time estimated by interview was below 6 hours, on at least 3 nights per week and for at least 1 month before screening
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- Baseline PSG (at randomization) assessed TST < 6 hours and WASO > 1 hour
- Diagnosis of MCI and AD patients at an early stage according to the NIA diagnosis criteria (core clinical criteria for MCI, positive CSF Aβ42 and/or positive plasma biomarker, and neuronal injury (hippocampal and/or temporal atrophy by MRI))
- MMSE from 12 to 26
- Clinical Dementia Rating CDR from 0.5 to 2
- Use of CNS-active medications is permitted provided the dose has been stable for at least 3 months, including: anticholinesterase drugs (rivastigmine, donepezil, galantamine) or memantine, antidepressants SSRI (e.g. fluoxetine, sertraline, paroxetine…), SNRI (e.g. venlafaxine, duloxetine), neuroleptics (e.g. clozapine, olanzapine, aripiprazole...) or drug for pain level 2 (codeine, tramadol).
- For a male subject who is not sterilized and is sexually active with a female partner of childbearing potential, no contraceptive methods are needed
- Non inclusion criteria :
- Patients significantly dependent on caregivers
- Institutionalized patients
- Analphabetism or subjects unable to read or/and write
- Patients unable to perform the neuropsychological tests
- Patients unable to complete the study instruments (sleep diary)
- Planned longer stay outside the region that prevents compliance with the visit schedule
- Patients who cannot be followed up for at least 2 months
- History of narcolepsy and/or cataplexy
- History of drug or alcohol abuse or addiction
- History of diagnosed and characterized psychiatric disorders (DSM-5), cured or stabilized (with or without the same treatment for at least 3 months) and excluding any current characterized psychiatric disorder (DSM-5), the diagnosis of which is established by a psychiatrist trained in geriatric psychiatry
- Moderate and severe liver failure
- PSG baseline evidence of significant/severe sleep-related breathing disorder (defined as >30 apnea/hypopnea episodes per hour)
- Treatments interfering with sleep-wake patterns
- Use of hypnotics (benzodiazepines, zolpidem, zopiclone) or drug for pain level 3 (morphine and derivatives)
- Hypersensitivity to the active substance or to any of the excipients listed in the Summary of Product Characteristics (SmPC)
- Forbidden and restricted concomitant medications:
- Concomitant CNS-depressant medicinal products
- CYP3A4 inhibitors
- CYP3A4 inducers
- Participation in another clinical trial or administration of an investigational product
- Protected population according to articles of the French Public Health Code (e.g. patients under law protection, prisoners, pregnant, parturient or lactating women, and patients under guardianship/curatorship).
- Subjects not covered by public health insurance
- Failure to obtain written informed consent after a reflection period
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
University Hospital, Montpellier
Montpellier
Yves DAUVILLIERS, MD, +33467336361, y-dauvilliers@chu-montpellier.fr
Yves DAUVILLIERS, MD
About this study
DARIDOR-ALZ is a phase IV clinical trial designed to evaluate both the efficacy and safety of daridorexant, a selective dual orexin receptor antagonist that blocks the actions of the orexin neuropeptides at both orexin-1 and orexin-2 receptors, in selected populations of MCI and mild-to-moderate AD patients with insomnia complaints.
Read the detailed description
This Phase IV clinical trial is a monocentric, randomized, double-blind, placebo-controlled, 2 way-crossover study (with two periods of one month separated by a washout period range from 5 to 12 days).The study population includes MCI and mild-to-moderate AD patients aged between 60 and 85 years old, with insomnia complaints.
A single-night baseline polysomnography recording will be performed from 11 pm to 7 am at the Montpellier Sleep Unit. After a baseline PSG that assessed TST < 6 hours and WASO > 1 hour, treatment will be assigned using an interactive response technology system.
A randomization list will be generated and will remain confidential until the database is locked. Participants, investigators, and site personnel will be unaware of treatment allocation during the two crossover periods. Patients will be randomized (1:1) to receive daridorexant 50 mg or placebo, without titration, every evening within 30 minutes of going to bed during both treatment periods (Treatment Period A and B) of one-month duration each. Each treatment period will be followed by a one-week (range 5-12 days) washout period at home.
A ten-month open-label (OL) study with daridorexant 50 mg will be proposed to all participants after completing the second treatment period. Based on the experience with another DORA study in patients with mild-to-moderate probable Alzheimer's disease, the investigators would need to recruit 62 patients (including drop-outs).
- Conditions
- Alzheimer Disease, Insomnia Disorder, Sleep
- Being tested
- Daridorexant 50 mg, Placebo, Polysomnography, Neuropsychological assessment, Questionnaires on sleep and behavioural problems
- Keywords
- Orexin, Daridorexant, Cognition, Alzheimer, Sleep, Insomnia
- Medical subject headings
- Alzheimer Disease, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daridorexant 50 mgDrug
Patients randomized in the experimental group will receive the treatment every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home.
PlaceboDrug
Patients randomized in the control group will receive the placebo every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home.
PolysomnographyProcedure or surgery
A full-night polysomnography recording with blood pressure and heart rate monitoring will be performed at night in the Sleep Laboratory from 11 p.m. to 7 a.m. at baseline (before the randomization) and at the end of each period (Period A/M1, Period B/M2). The recording procedure consists of an electroencephalogram, two electrooculograms, an electromyogram, an electrocardiogram, and a videographic recording. This examination is painless (the sensors are glued to the skin for the duration of the recording). The advantages of this video-polysomnography are based on the evaluation of sleep architecture, micro-arousals, respiratory events and nocturnal motor behavior.
Neuropsychological assessmentBehavioural
A full neuropsychological assessment will be performed at inclusion, M1, M2
Questionnaires on sleep and behavioural problemsBehavioural
Questionnaires on sleep and behavioural problems will be performed at inclusion, M1, M2
ActimetricsProcedure or surgery
Measurement of actimetrics for seven days in average (with a minimum of three nights required) prior to the inclusion visit, M1 visit and M2 visit.
24-hour Ambulatory Blood Pressure Monitoring (ABPMProcedure or surgery
Evaluation of the 24-hour hemodynamic profile of a patient by multiple and regular blood pressure and heart rate measurements. The ABP will be monitored at inclusion, M1 and M2
Biomarker assayOther
Determination of AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) in serum and cerebrospinal fluid (CSF) and dosage of Orexin-A/hypocretin-1 in the CSF
| Study group | Role | What they receive |
|---|---|---|
| Daridorexant 50 mg | Experimental | Patients will receive daridorexant 50 mg during one month (Period A or Period B).
Daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia. Receives: Drug: Daridorexant 50 mg; Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetrics; Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM; Other: Biomarker assay |
| Placebo-controlled arm | Placebo comparator | Patients will receive a placebo matching to daridorexant 50 mg during one month (Period A or Period B). Receives: Drug: Placebo; Procedure: Polysomnography; Behavioral: Neuropsychological assessment; Behavioral: Questionnaires on sleep and behavioural problems; Procedure: Actimetrics; Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM; Other: Biomarker assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Total Sleep Time (TST).
TST is defined as the total sleep time in minutes. The total sleep time is the total amount of sleep time scored during the total recording time. The TST is measured during polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Secondary outcomes (42)
Change in the wake time after sleep onset (WASO)
WASO is defined as the time to wake after initial sleep onset. WASO is measured during overnight sleep laboratory (PSG) assessment and defined as the duration of wakefulness from the onset of persistent sleep.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Change in Latency to Persistent Sleep (LPS)
LPS is the time in minutes from 'lights out' that marks the starting of total recording time to the first epoch recorded as sleep. The LPS is measured during polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Measure of sleep time at stage 1-2 during polysomnography
Time spent in stage 1-2 sleep measured in hours and minutes during polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Measure of sleep time at stage 3 during polysomnography
Time spent in stage 3 sleep measured in hours and minutes during polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Measure of number of wake bouts on the whole night
The number of wake bouts on the whole night will be measured by polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Measure of number of wake bouts per quarter of the night
The number of wake bouts per quarter of the night will be measured by polysomnography.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Changes in sleep and wake duration
Average sleep duration (in hours and minutes) over a 7-day period from inclusion to each visit measured by actimetry.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Changes in sleep and wake duration
Average sleep duration (in hours and minutes) over a 7-day period from inclusion to each visit measured by actimetry.
Measured: from baseline to Month 6
Changes in sleep and wake duration
Average sleep duration (in hours and minutes) over a 7-day period from inclusion to each visit measured by actimetry.
Measured: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ISI.
The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire assessing the nature, severity of both nighttime and daytime components of insomnia, and impact of insomnia.
Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ISI.
The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire assessing the nature, severity of both nighttime and daytime components of insomnia, and impact of insomnia.
Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).
Measured: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ISI.
The Insomnia Severity Index (ISI) is a 7-item self-report questionnaire assessing the nature, severity of both nighttime and daytime components of insomnia, and impact of insomnia.
Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).
Measured: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Epworth Sleepiness Scale (ESS)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ESS.
The Epworth Sleepiness Scale (ESS) is a self-report measure of daytime sleepiness in various situations and consists of eight questions. ESS score can range from 0 to 24 (1 to 6 points: Normal sleep; 7 to 8 points: Average sleepiness: 9 to 24 points: Abnormal (possibly pathologic) sleepiness).
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - ESS
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ESS.
The Epworth Sleepiness Scale (ESS) is a self-report measure of daytime sleepiness in various situations and consists of eight questions. ESS score can range from 0 to 24 (1 to 6 points: Normal sleep; 7 to 8 points: Average sleepiness: 9 to 24 points: Abnormal (possibly pathologic) sleepiness).
Measured: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Epworth Sleepiness Scale (ESS)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire ESS.
The Epworth Sleepiness Scale (ESS) is a self-report measure of daytime sleepiness in various situations and consists of eight questions. ESS score can range from 0 to 24 (1 to 6 points: Normal sleep; 7 to 8 points: Average sleepiness: 9 to 24 points: Abnormal (possibly pathologic) sleepiness).
Measured: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire IDSIQ.
The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a patient-reported outcome instrument that assesses daytime functioning in patients with insomnia.
It consists of 14 items (each using a numeric rating scale from 0 to 10) grouped into 3 domains : Alert/Cognition, Mood, and Sleepiness domain reflecting daytime impairment of insomnia.
The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire IDSIQ.
The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a patient-reported outcome instrument that assesses daytime functioning in patients with insomnia.
It consists of 14 items (each using a numeric rating scale from 0 to 10) grouped into 3 domains : Alert/Cognition, Mood, and Sleepiness domain reflecting daytime impairment of insomnia.
The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.
Measured: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire IDSIQ.
The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a patient-reported outcome instrument that assesses daytime functioning in patients with insomnia.
It consists of 14 items (each using a numeric rating scale from 0 to 10) grouped into 3 domains : Alert/Cognition, Mood, and Sleepiness domain reflecting daytime impairment of insomnia.
The IDSIQ sleepiness domain has 4 items, and the domain score ranges from 0 to a maximum of 40, where a higher score indicates a greater burden. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.
Measured: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire Sleep diaries.
Participants will completed a daily sleep diary (sleep onset latency, wake after sleep onset, early morning awakening, total wake time, total sleep time, and sleep efficiency).
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire Sleep diaries.
Participants will completed a daily sleep diary (sleep onset latency, wake after sleep onset, early morning awakening, total wake time, total sleep time, and sleep efficiency).
Measured: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Values and variations from baseline of patient-reported outcomes including self-reported questionnaire Sleep diaries.
Participants will completed a daily sleep diary (sleep onset latency, wake after sleep onset, early morning awakening, total wake time, total sleep time, and sleep efficiency).
Measured: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
The nocturnal agitation will be assessed by using the Neuropsychiatric Inventory (NPI) agitation/aggression domain.
The Neuropsychiatric Inventory (NPI), which consists of 12 items scored with questions, sub-questions, and frequency and severity ratings, is used to assess behavioral changes in Alzheimer disease and other neurodegenerative disorders. The agitation/aggression domain will be evaluated at each visit.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
The nocturnal agitation will be assessed by using the Neuropsychiatric Inventory (NPI) agitation/aggression domain.
The Neuropsychiatric Inventory (NPI), which consists of 12 items scored with questions, sub-questions, and frequency and severity ratings, is used to assess behavioral changes in Alzheimer disease and other neurodegenerative disorders. The agitation/aggression domain will be evaluated at each visit.
Measured: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
The nocturnal agitation will be assessed by using the Neuropsychiatric Inventory (NPI) agitation/aggression domain.
The Neuropsychiatric Inventory (NPI), which consists of 12 items scored with questions, sub-questions, and frequency and severity ratings, is used to assess behavioral changes in Alzheimer disease and other neurodegenerative disorders. The agitation/aggression domain will be evaluated at each visit.
Measured: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire BDI.
The Beck Depression Inventory (BDI) contains 21 items on a 4-point scale from 0 (symptom absent) to 3 (severe symptoms). The minimum score is 0 and the maximum score is 63, with a higher score indicating more severe depressive symptoms.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire BDI.
The Beck Depression Inventory (BDI) contains 21 items on a 4-point scale from 0 (symptom absent) to 3 (severe symptoms). The minimum score is 0 and the maximum score is 63, with a higher score indicating more severe depressive symptoms.
Measured: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire BDI.
The Beck Depression Inventory (BDI) contains 21 items on a 4-point scale from 0 (symptom absent) to 3 (severe symptoms). The minimum score is 0 and the maximum score is 63, with a higher score indicating more severe depressive symptoms.
Measured: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire EQ5D.
The EuroQol 5-dimensional descriptive system (EQ5D) is a Health Assessment Scale quality of life questionnaire evaluating: mobility, washing and dressing, daily activities, pain and anxiety. Each question has 3 levels of answers: No problem, some problems and important problems. Lower score indicate better outcomes.
The questionnaire also includes a visual analog scale in which the patient quantifies his or her perception of quality of life using a score ranging from the worst imaginable state of health (0) to the best imaginable state of health (100).
Measured: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire EQ5D.
The EuroQol 5-dimensional descriptive system (EQ5D) is a Health Assessment Scale quality of life questionnaire evaluating: mobility, washing and dressing, daily activities, pain and anxiety. Each question has 3 levels of answers: No problem, some problems and important problems. Lower score indicate better outcomes.
The questionnaire also includes a visual analog scale in which the patient quantifies his or her perception of quality of life using a score ranging from the worst imaginable state of health (0) to the best imaginable state of health (100).
Measured: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Values and variations from baseline of patient-reported outcomes including health assessment questionnaire EQ5D.
The EuroQol 5-dimensional descriptive system (EQ5D) is a Health Assessment Scale quality of life questionnaire evaluating: mobility, washing and dressing, daily activities, pain and anxiety. Each question has 3 levels of answers: No problem, some problems and important problems. Lower score indicate better outcomes.
The questionnaire also includes a visual analog scale in which the patient quantifies his or her perception of quality of life using a score ranging from the worst imaginable state of health (0) to the best imaginable state of health (100).
Measured: from baseline to Month 12
Change in cognition
The Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score will be based on scores from the Mini Mental State Examination (MMSE) (range from 0-30 points), Free and Cued Selective Reminding Test - FCSRT (range from 0-48 points), the Digit Substitution Symbol Test, the Wechsler Intelligence Scale for Adults (WAIS-IV) (range from 0-93 points), the Clinical Dementia Rating Scale (CDR) (range from 0-18 points), and the 2-minute Verbal Fluency Test.
The ADCS-PACC will be measured at each visit. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Change in cognition
The Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score will be based on scores from the Mini Mental State Examination (MMSE) (range from 0-30 points), Free and Cued Selective Reminding Test - FCSRT (range from 0-48 points), the Digit Substitution Symbol Test, the Wechsler Intelligence Scale for Adults (WAIS-IV) (range from 0-93 points), the Clinical Dementia Rating Scale (CDR) (range from 0-18 points), and the 2-minute Verbal Fluency Test.
The ADCS-PACC will be measured at each visit. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
Measured: from baseline to Month 6
Change in cognition
The Alzheimer's Disease Cooperative Study - Preclinical Alzheimer Cognitive (ADCS-PACC) scale score will be based on scores from the Mini Mental State Examination (MMSE) (range from 0-30 points), Free and Cued Selective Reminding Test - FCSRT (range from 0-48 points), the Digit Substitution Symbol Test, the Wechsler Intelligence Scale for Adults (WAIS-IV) (range from 0-93 points), the Clinical Dementia Rating Scale (CDR) (range from 0-18 points), and the 2-minute Verbal Fluency Test.
The ADCS-PACC will be measured at each visit. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. Z Scores could range from -5 to +5 with higher scores indicating less deficit and lower scores indicating greater deficit.
Measured: from baseline to Month 12
Change in blood pressure
Decrease in blood pressure variability (Systolic and Diastolic) during polysomnography and increase in 24-hour blood pressure monitoring dipping pattern from baseline to the end of each period (Month 1/Month 2) comparing daridorexant 50 mg with placebo.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Change in blood pressure
Change in 24-hour blood pressure (Systolic and Diastolic) monitoring dipping pattern from baseline to the month 6 with daridorexant 50 mg.
Measured: from baseline to Month 6
Change in blood pressure
Change in 24-hour blood pressure (Systolic and Diastolic) monitoring dipping pattern from baseline to the month 12 with daridorexant 50 mg.
Measured: from baseline to Month 12
Change in blood AD biomarkers and proinflammatory cytokines levels
Determination of blood AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) levels in serum.
Measured: from baseline to the end of each period A/B (Month1/Month2)
Change in blood AD biomarkers and proinflammatory cytokines levels
Determination of blood AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) levels in serum.
Measured: from baseline to Month 6
Change in blood AD biomarkers and proinflammatory cytokines levels
Determination of blood AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) levels in serum.
Measured: from baseline to Month 12
Concentration of CSF AD biomarkers and proinflammatory cytokines
Determination of AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) levels in cerebrospinal fluid (CSF).
Measured: baseline
Concentration of CSF orexinA/hypocretin
Determination orexinA/hypocretin in cerebrospinal fluid (CSF)
Measured: baseline
Percentage of Serious Adverse Events Occurring
Safety: rates of serious adverse events between baseline and 12 months.
Measured: between baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start13 Mar 2024
- Primary completion13 May 2027 (estimated)
- Study completion13 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- During Period A, patients randomized in the experimental group will receive the treatment every evening within 30 minutes of going to bed during one month. The treatment period will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the placebo. During Period A, patients randomized in the control group will receive the placebo every evening within 30 minutes of going to bed during one month. The treatment period will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the daridorexant 50 mg.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Idorsia Pharmaceuticals Ltd.
- Responsible party
- Sponsor
- Investigators
- Yves Dauvilliers, MD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05924425
- Sponsor's protocol ID
- RECHMPL22_0529
- Acronym
- DARIDOR-ALZ
- Status last verified
- Jun 2026
- First submitted
- 4 Jun 2023
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease
- ClinicalTrials.gov ID
- NCT05924425
- Acronym / sponsor ID
- DARIDOR-ALZ / RECHMPL22_0529
- Conditions
- Alzheimer Disease, Insomnia Disorder, Sleep
- Keywords
- Orexin, Daridorexant, Cognition, Alzheimer, Sleep, Insomnia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Idorsia Pharmaceuticals Ltd.
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- 13 May 2027 (estimated)
- Study completion
- 13 Mar 2028 (estimated)
- First posted
- 29 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DARIDOR-ALZ is a phase IV clinical trial designed to evaluate both the efficacy and safety of daridorexant, a selective dual orexin receptor antagonist that blocks the actions of the orexin neuropeptides at both orexin-1 and orexin-2 receptors, in selected populations of MCI and mild-to-moderate AD patients with insomnia complaints.
Detailed description
This Phase IV clinical trial is a monocentric, randomized, double-blind, placebo-controlled, 2 way-crossover study (with two periods of one month separated by a washout period range from 5 to 12 days).The study population includes MCI and mild-to-moderate AD patients aged between 60 and 85 years old, with insomnia complaints.
A single-night baseline polysomnography recording will be performed from 11 pm to 7 am at the Montpellier Sleep Unit. After a baseline PSG that assessed TST < 6 hours and WASO > 1 hour, treatment will be assigned using an interactive response technology system.
A randomization list will be generated and will remain confidential until the database is locked. Participants, investigators, and site personnel will be unaware of treatment allocation during the two crossover periods. Patients will be randomized (1:1) to receive daridorexant 50 mg or placebo, without titration, every evening within 30 minutes of going to bed during both treatment periods (Treatment Period A and B) of one-month duration each. Each treatment period will be followed by a one-week (range 5-12 days) washout period at home.
A ten-month open-label (OL) study with daridorexant 50 mg will be proposed to all participants after completing the second treatment period. Based on the experience with another DORA study in patients with mild-to-moderate probable Alzheimer's disease, the investigators would need to recruit 62 patients (including drop-outs).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- During Period A, patients randomized in the experimental group will receive the treatment every evening within 30 minutes of going to bed during one month. The treatment period will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the placebo. During Period A, patients randomized in the control group will receive the placebo every evening within 30 minutes of going to bed during one month. The treatment period will be followed by a one-week (range 5-12 days) washout period at home. During the second period (Period B), these patients will receive the daridorexant 50 mg.
| Arm | Type | Receives |
|---|---|---|
| Daridorexant 50 mg | Experimental | Drug: Daridorexant 50 mg, Procedure: Polysomnography, Behavioral: Neuropsychological assessment, Behavioral: Questionnaires on sleep and behavioural problems, Procedure: Actimetrics, Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM, Other: Biomarker assayPatients will receive daridorexant 50 mg during one month (Period A or Period B). Daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia. |
| Placebo-controlled arm | Placebo comparator | Drug: Placebo, Procedure: Polysomnography, Behavioral: Neuropsychological assessment, Behavioral: Questionnaires on sleep and behavioural problems, Procedure: Actimetrics, Procedure: 24-hour Ambulatory Blood Pressure Monitoring (ABPM, Other: Biomarker assayPatients will receive a placebo matching to daridorexant 50 mg during one month (Period A or Period B). |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Age [60-85] years old
- Outpatients
- Pre-screening:
- Baseline PSG (at randomization) assessed TST < 6 hours and WASO > 1 hour
- Diagnosis of MCI and AD patients at an early stage according to the NIA diagnosis criteria (core clinical criteria for MCI, positive CSF Aβ42 and/or positive plasma biomarker, and neuronal injury (hippocampal and/or temporal atrophy by MRI))
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daridorexant 50 mgPatients randomized in the experimental group will receive the treatment every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home. | Drug | Daridorexant 50 mg |
| PlaceboPatients randomized in the control group will receive the placebo every evening within 30 minutes of going to bed during one month. The treatment period (Period A or Period B) will be followed by a one-week (range 5-12 days) washout period at home. | Drug | Placebo-controlled arm |
| PolysomnographyA full-night polysomnography recording with blood pressure and heart rate monitoring will be performed at night in the Sleep Laboratory from 11 p.m. to 7 a.m. at baseline (before the randomization) and at the end of each period (Period A/M1, Period B/M2). The recording procedure consists of an electroencephalogram, two electrooculograms, an electromyogram, an electrocardiogram, and a videographic recording. This examination is painless (the sensors are glued to the skin for the duration of the recording). The advantages of this video-polysomnography are based on the evaluation of sleep architecture, micro-arousals, respiratory events and nocturnal motor behavior. | Procedure or surgery | Daridorexant 50 mg, Placebo-controlled arm |
| Neuropsychological assessmentA full neuropsychological assessment will be performed at inclusion, M1, M2 | Behavioural | Daridorexant 50 mg, Placebo-controlled arm |
| Questionnaires on sleep and behavioural problemsQuestionnaires on sleep and behavioural problems will be performed at inclusion, M1, M2 | Behavioural | Daridorexant 50 mg, Placebo-controlled arm |
| ActimetricsMeasurement of actimetrics for seven days in average (with a minimum of three nights required) prior to the inclusion visit, M1 visit and M2 visit. | Procedure or surgery | Daridorexant 50 mg, Placebo-controlled arm |
| 24-hour Ambulatory Blood Pressure Monitoring (ABPMEvaluation of the 24-hour hemodynamic profile of a patient by multiple and regular blood pressure and heart rate measurements. The ABP will be monitored at inclusion, M1 and M2 | Procedure or surgery | Daridorexant 50 mg, Placebo-controlled arm |
| Biomarker assayDetermination of AD biomarkers (Aβ42, Aβ40, Tau, P-Tau, neurofilament) and proinflammatory cytokines (TNFa, IL6) in serum and cerebrospinal fluid (CSF) and dosage of Orexin-A/hypocretin-1 in the CSF | Other | Daridorexant 50 mg, Placebo-controlled arm |
Primary outcome
Change in Total Sleep Time (TST).
Time frame: from baseline to the end of each period A/B (Month1/Month2)
TST is defined as the total sleep time in minutes. The total sleep time is the total amount of sleep time scored during the total recording time. The TST is measured during polysomnography.
42 secondary outcomes
Change in the wake time after sleep onset (WASO)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Change in Latency to Persistent Sleep (LPS)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Measure of sleep time at stage 1-2 during polysomnography
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Measure of sleep time at stage 3 during polysomnography
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Measure of number of wake bouts on the whole night
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Measure of number of wake bouts per quarter of the night
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Changes in sleep and wake duration
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Changes in sleep and wake duration
Time frame: from baseline to Month 6
Changes in sleep and wake duration
Time frame: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Time frame: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Insomnia Severity Index (ISI)
Time frame: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Epworth Sleepiness Scale (ESS)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - ESS
Time frame: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Epworth Sleepiness Scale (ESS)
Time frame: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Time frame: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Insomnia Daytime Symptoms and Impacts (IDSIQ)
Time frame: from baseline to Month 12
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Time frame: from baseline to Month 6
Variations in the results of self-reported questionnaires administered to patients - Sleep Diaries
Time frame: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
Time frame: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - Neuropsychiatric Inventory (NPI)
Time frame: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Time frame: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - Beck Depression Inventory (BDI)
Time frame: from baseline to Month 12
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Time frame: from baseline to Month 6
Variations in the results of health assessment questionnaires administered to patients - EuroQoL-5D (EQ5D)
Time frame: from baseline to Month 12
Change in cognition
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Change in cognition
Time frame: from baseline to Month 6
Change in cognition
Time frame: from baseline to Month 12
Change in blood pressure
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Change in blood pressure
Time frame: from baseline to Month 6
Change in blood pressure
Time frame: from baseline to Month 12
Change in blood AD biomarkers and proinflammatory cytokines levels
Time frame: from baseline to the end of each period A/B (Month1/Month2)
Change in blood AD biomarkers and proinflammatory cytokines levels
Time frame: from baseline to Month 6
Change in blood AD biomarkers and proinflammatory cytokines levels
Time frame: from baseline to Month 12
Concentration of CSF AD biomarkers and proinflammatory cytokines
Time frame: baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yves Dauvilliers, MD principal investigator
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Daridorexant 50 mg, Polysomnography and Neuropsychological assessment in people with Alzheimer Disease and Insomnia Disorder, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yves Dauvilliers, MD (+33467336361, y-dauvilliers@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Total Sleep Time (TST). (time frame: from baseline to the end of each period A/B (Month1/Month2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.