DepressionPhase 4DEP-CINCT01658228
Combination Treatment Study for Memory Impairment and Depression
A Phase 4 study testing Donepezil, Citalopram and Venlafaxine in people with Depression and Mild Cognitive Impairment, run by New York State Psychiatric Institute at 2 sites in United States.
Trial summary
Patients presenting with depression (DEP) and cognitive impairment (CI), represent a unique, understudied population that is difficult to diagnose, treat and estimate prognosis. Our pilot data, supported by the literature, suggest that many DEP-CI patients show cognitive decline and often convert to dementia… Read more about this study
- Who is it for?
- Ages 55 to 95 years
- Conditions the study is for
- Depression, Mild Cognitive Impairment
- What is being tested?
- Donepezil, Citalopram and Venlafaxine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2011to Jan 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Of either sex, age 55-95 years old with minimum 8 years of education who meet criteria for both depression and cognitive impairment as described below.
- Study Criteria for "depression":
- Patients who meet DSM-IV symptom criteria for Major Depression or Dysthymia for a minimum of 6 months (2 year duration DSM-IV TR criterion not required for dysthymic disorder in this study). ii. 24-item HAM-D ≥14.
- Study Criteria for "cognitive impairment":
- Subjective memory or other cognitive complaints. ii. Score ≤ 11 on the Logical Memory II (Delayed Paragraph Recall, Paragraph A) test from the Wechsler Memory Scale - Revised OR a score that is ≥ 1.5 standard deviations below the norms on the FC SRT
- Folstein Mini Mental State (MMSE) score ≥ 21 out of 30.
Show all 9Show fewer
- Clinical Dementia Rating (CDR) of 0.5 on the memory item and global rating of 0.5 indicating questionable dementia
- Willing and capable of giving informed consent
- A family member or close friend who consents to serve as informant during the study; this can be a telephone informant in the case of patients who do not have a live-in informant or close significant other.
Who cannot join
- Meets Criteria for dementia (DSM-IV) or probable Alzheimer's disease (NINCDS-ADRDA criteria)
- Meets DSM IV TR criteria for:
- schizophrenia, schizoaffective disorder, psychotic depression or other psychosis, or bipolar I disorder
- alcohol or substance dependence or abuse (current or within past 6 months)
- Active suicidal ideation or suicidal attempt in last 6 months.
- Clinical stroke with residual neurological deficits.
Show all 10Show fewer
- Use of medications known to have a negative impact on cognition: benzodiazepines in lorazepam equivalents ≥ 2 mg daily, narcotics, or anticholinergics. (N.B. Medications that may be associated with cognitive impairment but are rarely considered the likely etiology, e.g, theophylline, nifedipine, Beta blockers, will not be excluded.)
- An acute, severe or unstable medical condition. For cancer, acutely ill patients (including those with metastases) are excluded, but past history of successfully treated cancer does not result in exclusion.
- Presence of any of the following disorders: a) CNS infection, with CSF evidence of meningitis, encephalitis, or other infectious process; b) Post-traumatic dementia, defined as dementia with a clear temporal relationship to a severe head injury where consciousness was lost; c) Huntington's disease; d) Multiple sclerosis; e) Parkinson's disease; f) Other neurologic disorders with focal signs, e.g., amyotrophic lateral sclerosis; g) Mental retardation.
- Contra-indication to MRI scan: pacemaker, metal implants following surgery, any other contraindication to MRI (e.g., ferromagnetic aneurysm clips, heart valves). For patients with possible claustrophobia, they can do the MRI with adjunct lorazepam 0.5 mg to reduce anxiety. Patients who cannot do the MRI scan will still be eligible for the clinical trial, i.e., MRI is optional.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University
Durham, North Carolina, 27710
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Pilot Combination Treatment Trial of Mild Cognitive Impairment With Depression
Patients presenting with depression (DEP) and cognitive impairment (CI), represent a unique, understudied population that is difficult to diagnose, treat and estimate prognosis. Our pilot data, supported by the literature, suggest that many DEP-CI patients show cognitive decline and often convert to dementia, primarily Alzheimer's disease (AD). In DEP-CI, there is a lack of data on treatment response of mood symptoms to antidepressant treatment and particularly of cognitive deficits to cognitive enhancer treatment. Our initial pilot data in a double-blind study showed that donepezil was superior to placebo in improving memory in antidepressant-treated DEP-CI patients. In a second pilot study, open label es-citalopram plus memantine treatment led to a low rate of conversion to dementia.
In this proposed pilot clinical trial, the investigators will evaluate, treat and follow a broad sample of 80 DEP-CI patients at NYSPI/Columbia University Medical Center (N = 40) and Duke University Medical Center (N = 40). Recruitment will be from clinics and/or advertisements. In the treatment protocol, all 80 DEP-CI patients will receive baseline mood and memory assessments and open antidepressant treatment with citalopram for 8 weeks. At 8 weeks, repeat assessment will occur and patients whose depression has responded to citalopram will be randomized to add-on donepezil or placebo. Non-responders to citalopram will receive open treatment with venlafaxine and will be randomized 8 weeks later (16 weeks of open antidepressant treatment) to add-on donepezil or placebo. Patients will be followed for a total period of 18 months with continuous open antidepressant treatment during the trial.
Donepezil is being studied in order to increase the likelihood of obtaining a signal. If the results are positive, the investigators can begin clarifying the mechanism(s) in subsequent trials. Baseline apolipoprotein E e4 genotype, odor identification deficits, and MRI hippocampal and entorhinal cortex atrophy will be explored as predictors of donepezil response in the 18-month trial. Improving cognition and delaying conversion to a clinical diagnosis of dementia in this high risk group will enhance quality of life, reduce family burden, and markedly diminish overall health care costs.
Read the detailed description
In the elderly, the most common neuropsychiatric disorders are depression (DEP) and cognitive impairment (CI). Their co-occurrence (DEP-CI) may exceed chance. The lack of research in DEP-CI, the need to determine early prognostic indicators, and to develop optimal treatment strategies, was emphasized by a NIH consensus panel. Since depression in patients with CI increases the risk of conversion to dementia, treatment strategies for DEP-CI have longer-term implications beyond acute antidepressant treatment response. However, in DEP-CI, there is a lack of data on treatment response of mood symptoms to antidepressant treatment and of cognitive deficits to cognitive enhancer treatment, and the long-term prognosis in these patients remains unclear. The investigators have initial pilot data showing that donepezil was superior to placebo in improving memory performance in DEP-CI patients, and pilot data showing that patients with DEP-CI treated with combined escitalopram and memantine have a low conversion rate to dementia, primarily Alzheimer's disease (AD), over one year. This proposal is for the first study to explicitly examine cognitive change, including conversion to dementia, in a randomized, double-blind, placebo-controlled donepezil treatment trial in DEP-CI patients treated openly with antidepressants. The investigators will conduct systematic follow-up to evaluate 18-month outcome. In addition to apolipoprotein E ε4 genotype, the investigators will explore MRI hippocampal and entorhinal cortex atrophy and odor identification deficits as biomarkers that moderate response.
This pilot trial will enroll about 80 DEP-CI patients who present to the departments of Psychiatry, Neurology and Internal Medicine at NYSPI/Columbia University and Duke University medical centers, ensuring broad representation for clinical relevance. In the treatment protocol, all 80 DEP-CI patients will receive open antidepressant treatment with citalopram for 8 weeks. At 8 weeks, citalopram responders will continue to be treated on citalopram, while non-responders will switch to venlafaxine treatment for an additional 8 weeks. At 16 weeks, all subjects will be randomized to add-on donepezil or placebo (N.B. Patients with a prior history of nonresponse to both citalopram and venlafaxine will be enrolled in the protocol and treated with bupropion and subsequently with doctor's choice of antidepressant). Patients will be followed for a total period of up to 18 months in the trial, with antidepressant treatment adjusted as needed based on clinical response and side effects, i.e., open antidepressant treatment is continuous for all subjects throughout the trial and is not the experimental intervention. The investigators chose to study antidepressant plus donepezil compared to placebo based on our pilot data and to increase the likelihood of obtaining a signal.
Aim 1 (primary aim of the study). To assess change in cognitive status over 18 months in antidepressant-treated DEP-CI patients comparing donepezil to placebo.
Hypothesis 1. Antidepressant-treated DEP-CI patients on donepezil will show a lower rate of conversion to dementia, primarily AD, compared to antidepressant-treated DEP-CI patients on placebo by the end of the 18-month trial.
Hypothesis 2 (secondary). Compared to the placebo group, the donepezil group will show better cognitive outcome by the end of the 18-month trial (SRT total recall: primary measure; modified ADAS-cog: secondary measure).
Hypothesis 3 (secondary). At the end of 24 weeks on add-on donepezil or placebo, the donepezil group will show better cognitive outcome than placebo (SRT total recall: primary measure; modified ADAS-cog: secondary measure).
Aim 2: To evaluate moderators of treatment on cognitive change in the 18-month donepezil-placebo trial, based on the view that patients with incipient AD brain pathology will have superior cognitive outcome on donepezil. These Aim 2 hypotheses are considered exploratory.
Hypothesis 1. Patients with the apolipoprotein E ε4 allele (homozygote or heterozygote), compared to patients without this allele, will have better cognitive outcome on donepezil compared to placebo.
Hypothesis 2. Lower scores on the UPSIT (odor identification test) at baseline will be associated with better cognitive outcome on donepezil compared to placebo.
Hypothesis 3. Smaller MRI hippocampal and entorhinal cortex volumes (atrophy) will be associated with better cognitive outcome on donepezil compared to placebo.
- Conditions
- Depression, Mild Cognitive Impairment
- Being tested
- Donepezil, Placebo, Citalopram, Venlafaxine
- Keywords
- Depression, Dysthymia, Cognitive Impairment, Cognitive Decline, Memory
- Medical subject headings
- Depression, Cognitive Dysfunction, Dysthymic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called Aricept
Donepezil 5mg will be given for 6 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg per day is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease.
PlaceboDrug
A placebo capsule will be given to randomized subjects for the starting at week 16 and continuing for the remainder of the study. This group will not receive donepezil as treatment.
CitalopramDrug
Citalopram tablet will be given to subjects during an 8 week flexible dosing open treatment. If subjects respond to citalopram treatment they will be randomized to add-on donepezil/placebo.
VenlafaxineDrug
Venlafaxine tablet will be given to subjects during an 8 week flexible dosing open treatment if they did not respond to citalopram. If subjects respond to venlafaxine treatment they will be randomized to add-on donepezil/placebo.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil Treatment Group | Other | For the initial 16 weeks of open-label antidepressant treatment, citalopram up to 20 mg daily or venlafaxine up to 225 mg daily was prescribed. At 16 weeks, all patients were randomized, double-blind, to add-on donepezil or placebo for 62 weeks. Donepezil was started at 5 mg and increased to 10 mg daily or maximum tolerated dose while continuing antidepressants. Receives: Drug: Donepezil |
| Placebo Treatment Group | Other | For the initial 16 weeks of open-label antidepressant treatment, citalopram up to 20 mg daily or venlafaxine up to 225 mg daily was prescribed. At 16 weeks, all patients were randomized, double-blind, to add-on donepezil or placebo for 62 weeks. Placebo dose was increased during the study to match Donepezil dose increases while continuing antidepressants. Receives: Drug: Placebo |
| Citalopram | Other | An open treatment 8 week flexible dosing schedule starting with citalopram 10mg/day for the first week, then increasing to 20 mg/day thereafter to treat the depression. At the week 8 visit, citalopram responders will continue citalopram treatment and will be randomized to add-on donepezil or placebo at the week 16 visit. Receives: Drug: Citalopram |
| Venlafaxine | Other | For patients who did not respond to citalopram, open treatment 8 week flexible dosing schedule starting with venlafaxine 37.5mg/day for the first week, then 75mg/day for the second week, then 150mg/day for the third and fourth week, then 225mg/day for the fifth through eighth weeks. At the end of the eighth week, we will assess patients for antidepressant response. At this time-point, venlafaxine responders will be randomized to add-on donepezil or placebo. Receives: Drug: Venlafaxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Selective Reminding Test (SRT) Total Recall
The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall) was obtained.
Measured: Week 16
Selective Reminding Test (SRT) Delayed Recall
The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall) and delayed recall (after a 15-minute delay) was obtained.
Measured: Week 16
Secondary outcomes (1)
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation. Subjects' scores represent the total number of errors made throughout the various tasks. The total number of possible errors is between 0-85.
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2012 (estimated)
- Study startSep 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Davangere Devanand, MD, Principal investigator, Columbia UniversityGregory Pelton, MD, Study director, Columbia UniversitySteven Roose, MD, Study director, Columbia UniversityMurali Doraiswamy, MD, Study director, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01658228
- Sponsor's protocol ID
- #6459
- Other IDs
- R01AG040093-01
- Acronym
- DEP-CI
- Status last verified
- Oct 2017
- First submitted
- 30 Jul 2012
- Last updated
- 17 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Devanand DP, Pelton GH, D'Antonio K, Ciarleglio A, Scodes J, Andrews H, Lunsford J, Beyer JL, Petrella JR, Sneed J, Ciovacco M, Doraiswamy PM. Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial. Am J Geriatr Psychiatry. 2018 Oct;26(10):1050-1060. doi: 10.1016/j.jagp.2018.05.008. Epub 2018 Jun 28.
PubMed 30037778Pelton GH, Andrews H, Roose SP, Marcus SM, D'Antonio K, Husn H, Petrella JR, Zannas AS, Doraiswamy PM, Devanand DP. Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design. Contemp Clin Trials. 2014 Mar;37(2):200-8. doi: 10.1016/j.cct.2013.11.015. Epub 2013 Dec 5.
PubMed 24315979
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Combination Treatment Trial of Mild Cognitive Impairment With Depression
- ClinicalTrials.gov ID
- NCT01658228
- Acronym / sponsor ID
- DEP-CI / #6459
- Conditions
- Depression, Mild Cognitive Impairment
- Keywords
- Depression, Dysthymia, Cognitive Impairment, Cognitive Decline, Memory
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Sep 2011
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 6 Aug 2012 (estimated)
- Results
- Posted 17 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients presenting with depression (DEP) and cognitive impairment (CI), represent a unique, understudied population that is difficult to diagnose, treat and estimate prognosis. Our pilot data, supported by the literature, suggest that many DEP-CI patients show cognitive decline and often convert to dementia, primarily Alzheimer's disease (AD). In DEP-CI, there is a lack of data on treatment response of mood symptoms to antidepressant treatment and particularly of cognitive deficits to cognitive enhancer treatment. Our initial pilot data in a double-blind study showed that donepezil was superior to placebo in improving memory in antidepressant-treated DEP-CI patients. In a second pilot study, open label es-citalopram plus memantine treatment led to a low rate of conversion to dementia.
In this proposed pilot clinical trial, the investigators will evaluate, treat and follow a broad sample of 80 DEP-CI patients at NYSPI/Columbia University Medical Center (N = 40) and Duke University Medical Center (N = 40). Recruitment will be from clinics and/or advertisements. In the treatment protocol, all 80 DEP-CI patients will receive baseline mood and memory assessments and open antidepressant treatment with citalopram for 8 weeks. At 8 weeks, repeat assessment will occur and patients whose depression has responded to citalopram will be randomized to add-on donepezil or placebo. Non-responders to citalopram will receive open treatment with venlafaxine and will be randomized 8 weeks later (16 weeks of open antidepressant treatment) to add-on donepezil or placebo. Patients will be followed for a total period of 18 months with continuous open antidepressant treatment during the trial.
Donepezil is being studied in order to increase the likelihood of obtaining a signal. If the results are positive, the investigators can begin clarifying the mechanism(s) in subsequent trials. Baseline apolipoprotein E e4 genotype, odor identification deficits, and MRI hippocampal and entorhinal cortex atrophy will be explored as predictors of donepezil response in the 18-month trial. Improving cognition and delaying conversion to a clinical diagnosis of dementia in this high risk group will enhance quality of life, reduce family burden, and markedly diminish overall health care costs.
Detailed description
In the elderly, the most common neuropsychiatric disorders are depression (DEP) and cognitive impairment (CI). Their co-occurrence (DEP-CI) may exceed chance. The lack of research in DEP-CI, the need to determine early prognostic indicators, and to develop optimal treatment strategies, was emphasized by a NIH consensus panel. Since depression in patients with CI increases the risk of conversion to dementia, treatment strategies for DEP-CI have longer-term implications beyond acute antidepressant treatment response. However, in DEP-CI, there is a lack of data on treatment response of mood symptoms to antidepressant treatment and of cognitive deficits to cognitive enhancer treatment, and the long-term prognosis in these patients remains unclear. The investigators have initial pilot data showing that donepezil was superior to placebo in improving memory performance in DEP-CI patients, and pilot data showing that patients with DEP-CI treated with combined escitalopram and memantine have a low conversion rate to dementia, primarily Alzheimer's disease (AD), over one year. This proposal is for the first study to explicitly examine cognitive change, including conversion to dementia, in a randomized, double-blind, placebo-controlled donepezil treatment trial in DEP-CI patients treated openly with antidepressants. The investigators will conduct systematic follow-up to evaluate 18-month outcome. In addition to apolipoprotein E ε4 genotype, the investigators will explore MRI hippocampal and entorhinal cortex atrophy and odor identification deficits as biomarkers that moderate response.
This pilot trial will enroll about 80 DEP-CI patients who present to the departments of Psychiatry, Neurology and Internal Medicine at NYSPI/Columbia University and Duke University medical centers, ensuring broad representation for clinical relevance. In the treatment protocol, all 80 DEP-CI patients will receive open antidepressant treatment with citalopram for 8 weeks. At 8 weeks, citalopram responders will continue to be treated on citalopram, while non-responders will switch to venlafaxine treatment for an additional 8 weeks. At 16 weeks, all subjects will be randomized to add-on donepezil or placebo (N.B. Patients with a prior history of nonresponse to both citalopram and venlafaxine will be enrolled in the protocol and treated with bupropion and subsequently with doctor's choice of antidepressant). Patients will be followed for a total period of up to 18 months in the trial, with antidepressant treatment adjusted as needed based on clinical response and side effects, i.e., open antidepressant treatment is continuous for all subjects throughout the trial and is not the experimental intervention. The investigators chose to study antidepressant plus donepezil compared to placebo based on our pilot data and to increase the likelihood of obtaining a signal.
Aim 1 (primary aim of the study). To assess change in cognitive status over 18 months in antidepressant-treated DEP-CI patients comparing donepezil to placebo.
Hypothesis 1. Antidepressant-treated DEP-CI patients on donepezil will show a lower rate of conversion to dementia, primarily AD, compared to antidepressant-treated DEP-CI patients on placebo by the end of the 18-month trial.
Hypothesis 2 (secondary). Compared to the placebo group, the donepezil group will show better cognitive outcome by the end of the 18-month trial (SRT total recall: primary measure; modified ADAS-cog: secondary measure).
Hypothesis 3 (secondary). At the end of 24 weeks on add-on donepezil or placebo, the donepezil group will show better cognitive outcome than placebo (SRT total recall: primary measure; modified ADAS-cog: secondary measure).
Aim 2: To evaluate moderators of treatment on cognitive change in the 18-month donepezil-placebo trial, based on the view that patients with incipient AD brain pathology will have superior cognitive outcome on donepezil. These Aim 2 hypotheses are considered exploratory.
Hypothesis 1. Patients with the apolipoprotein E ε4 allele (homozygote or heterozygote), compared to patients without this allele, will have better cognitive outcome on donepezil compared to placebo.
Hypothesis 2. Lower scores on the UPSIT (odor identification test) at baseline will be associated with better cognitive outcome on donepezil compared to placebo.
Hypothesis 3. Smaller MRI hippocampal and entorhinal cortex volumes (atrophy) will be associated with better cognitive outcome on donepezil compared to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Donepezil Treatment Group | Other | Drug: DonepezilFor the initial 16 weeks of open-label antidepressant treatment, citalopram up to 20 mg daily or venlafaxine up to 225 mg daily was prescribed. At 16 weeks, all patients were randomized, double-blind, to add-on donepezil or placebo for 62 weeks. Donepezil was started at 5 mg and increased to 10 mg daily or maximum tolerated dose while continuing antidepressants. |
| Placebo Treatment Group | Other | Drug: PlaceboFor the initial 16 weeks of open-label antidepressant treatment, citalopram up to 20 mg daily or venlafaxine up to 225 mg daily was prescribed. At 16 weeks, all patients were randomized, double-blind, to add-on donepezil or placebo for 62 weeks. Placebo dose was increased during the study to match Donepezil dose increases while continuing antidepressants. |
| Citalopram | Other | Drug: CitalopramAn open treatment 8 week flexible dosing schedule starting with citalopram 10mg/day for the first week, then increasing to 20 mg/day thereafter to treat the depression. At the week 8 visit, citalopram responders will continue citalopram treatment and will be randomized to add-on donepezil or placebo at the week 16 visit. |
| Venlafaxine | Other | Drug: VenlafaxineFor patients who did not respond to citalopram, open treatment 8 week flexible dosing schedule starting with venlafaxine 37.5mg/day for the first week, then 75mg/day for the second week, then 150mg/day for the third and fourth week, then 225mg/day for the fifth through eighth weeks. At the end of the eighth week, we will assess patients for antidepressant response. At this time-point, venlafaxine responders will be randomized to add-on donepezil or placebo. |
Who may qualify
- Ages
- 55 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Of either sex, age 55-95 years old with minimum 8 years of education who meet criteria for both depression and cognitive impairment as described below.
- Study Criteria for "depression":
- Study Criteria for "cognitive impairment":
- Folstein Mini Mental State (MMSE) score ≥ 21 out of 30.
- Clinical Dementia Rating (CDR) of 0.5 on the memory item and global rating of 0.5 indicating questionable dementia
Key exclusion criteria (10 listed)
- Meets Criteria for dementia (DSM-IV) or probable Alzheimer's disease (NINCDS-ADRDA criteria)
- Meets DSM IV TR criteria for:
- Active suicidal ideation or suicidal attempt in last 6 months.
- Clinical stroke with residual neurological deficits.
- Use of medications known to have a negative impact on cognition: benzodiazepines in lorazepam equivalents ≥ 2 mg daily, narcotics, or anticholinergics. (N.B. Medications that may be associated with cognitive impairment but are rarely considered the likely etiology, e.g, theophylline, nifedipine, Beta blockers, will not be excluded.)
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 |
|---|---|---|
| DonepezilAlso: AriceptDonepezil 5mg will be given for 6 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg per day is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. | Drug | Donepezil Treatment Group |
| PlaceboA placebo capsule will be given to randomized subjects for the starting at week 16 and continuing for the remainder of the study. This group will not receive donepezil as treatment. | Drug | Placebo Treatment Group |
| CitalopramCitalopram tablet will be given to subjects during an 8 week flexible dosing open treatment. If subjects respond to citalopram treatment they will be randomized to add-on donepezil/placebo. | Drug | Citalopram |
| VenlafaxineVenlafaxine tablet will be given to subjects during an 8 week flexible dosing open treatment if they did not respond to citalopram. If subjects respond to venlafaxine treatment they will be randomized to add-on donepezil/placebo. | Drug | Venlafaxine |
Primary outcome
Selective Reminding Test (SRT) Total Recall
Time frame: Week 16
The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall) was obtained.
Selective Reminding Test (SRT) Delayed Recall
Time frame: Week 16
The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall) and delayed recall (after a 15-minute delay) was obtained.
1 secondary outcome
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Time frame: Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30037778Devanand DP, Pelton GH, D'Antonio K, Ciarleglio A, Scodes J, Andrews H, Lunsford J, Beyer JL, Petrella JR, Sneed J, Ciovacco M, Doraiswamy PM. Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial. Am J Geriatr Psychiatry. 2018 Oct;26(10):1050-1060. doi: 10.1016/j.jagp.2018.05.008. Epub 2018 Jun 28.
- Derived from this study: PubMed 24315979Pelton GH, Andrews H, Roose SP, Marcus SM, D'Antonio K, Husn H, Petrella JR, Zannas AS, Doraiswamy PM, Devanand DP. Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design. Contemp Clin Trials. 2014 Mar;37(2):200-8. doi: 10.1016/j.cct.2013.11.015. Epub 2013 Dec 5.
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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. This study is not recruiting at the moment.
Davangere Devanand, MD principal investigator
Columbia University
Gregory Pelton, MD study director
Columbia University
Steven Roose, MD study director
Columbia University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Donepezil, Citalopram and Venlafaxine in people with Depression and Mild Cognitive Impairment, run by New York State Psychiatric Institute at 2 sites in United States.
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 9 inclusion and 10 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: finished, as of the sponsor's last update on 17 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. 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?
Yes. Results are posted in the registry (first posted 17 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Selective Reminding Test (SRT) Total Recall (time frame: Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01658228, which also lists 2 linked publications.
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 17 Oct 2017.