Alzheimer DiseasePhase 1NCT03274817
A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol
A Phase 1 study testing Escitalopram Pill and Venlafaxine Pill in people with Alzheimer Disease, run by NYU Langone Health at 1 site in United States.
Trial summary
This is an investigator-initiated study comparing two types of FDA-approved anti-depressants, Escitalopram and Venlafaxine, to placebo, in order to determine if these medications have positive effects on cognition and memory in those who are between the ages of 50 to 89 years old, who are cognitively normal, and who… Read more about this study
- Who is it for?
- Ages 60 to 80 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Escitalopram Pill and Venlafaxine Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2009to 25 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have subjective cognitive impairment (SCI) and be free of objective evidence of cognitive impairment. Operationally, this will be defined as subjects with Global Deterioration Scale (GDS) score of stage 2.4
- Subjects must be between 60 and 80 years of age.
- Subjects must have a knowledgeable informant (study partner) who can accompany them to the evaluations, or, when necessary, be available for telephone contact.
- Subjects must be otherwise healthy and fulfill all of the inclusion criteria for participation in the NYU ADC. Exclusion criteria are enumerated below.
- Subjects must be in a position to comply with all of the study procedures described herein.
- Subjects must have a minimum of 12 years of education.
- Subjects must be fluent in English.
- Subjects original language at birth and/or, in childhood, must have been English, alone, or in conjunction with other languages.
Who cannot join
- Subjects who have normal brain aging, who are free of subjective cognitive impairment (SCI), and are therefore categorized at GDS stage 1, will be excluded.
- Subjects with MCI or dementia and are therefore categorized as being at GDS stage 3 or greater, will be excluded.
- Subjects with a mini mental status examination (MMSE) score61 of ≤ 27 will be excluded.
- Subjects with a Hamilton Depression Scale (HDS) score ≥ 16,62 signifying the presence of notable depressive symptomatology which warrants treatment, will be excluded.
- Subjects with a primary diagnosis of depression or with a major depression diagnosis will be excluded.
- Subjects with a significant medical, neurologic, or psychiatric condition, including depression or anxiety disorder, that might interfere with cognition will be excluded.
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- Subjects with a history of adverse reactions to escitalopram and/or venlaflaxine will be excluded.
- Subjects, who are judged to have had adverse reactions to selective serotonin reuptake inhibitor medications as a class, will be excluded.
- Subjects taking the antibiotic Zyvox (linezolid) or methylene blue therapy or who are planning to have a diagnostic procedure utilizing methylene blue dye, will be excluded.
- Subjects who are on psychoactive or cognitively active medications or who have received such medications in the prior 8 weeks, will be excluded. These excluded medications encompass antidepressant medications, antipsychotic medications, anxiolytic medications, cholinesterase inhibitors, memantine, antiseizure medications, antiparkinsonian medication and other CNS acting medications.
- Subjects who are receiving other medications or substances with reported neurogenic enhancer or neurogenic inhibitor effects will not be excluded. The reason for this inclusionary approach is that just as the effects of neurogenic enhancers on Alzheimer's disease appears to be complex (specifically, likely useful in prevention, possibly not useful effects on disease progression), the same complexity apparently applies to substances with reported neurogenic enhancer or inhibitor effects. For example, the angiotensin II receptor antagonist losartan has been reported to suppress running enhanced neurogenesis in the rat.63 This same medication and medication class has also been reported to be useful in improving memory64 and in the prevention of Alzheimer's disease, possibly by other mechanisms.65
- Subjects with a history of significant cerebrovascular disease will be excluded. This will be identified by one of the following:
- history of stroke. ii. Any focal signs of significant neuropathology from the neurological examination.
- A score of ≥ 4 on the Rosen modification of the Hachinski Ischemia Scale.66 iv. Focal pathology on the MRI scan, indicative of history of infarction. l. Past history of brain damage, seizure, mental retardation or serious neurological disorders.
- Significant history of alcoholism or drug abuse.
- Previous history of schizophrenia, mania, or major depression.
- Severe cardiac, pulmonary, vascular, metabolic, or hematologic conditions.
- Presence of a cardiac pacemaker.
- Presence of any metallic device or implant which would contraindicate an MRI (magnetic resonance imaging) scan of the brain.
- Physical impairment of such severity as to adversely affect the validity of psychological testing.
- Hostility or refusal to cooperate.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine
New York, New York, 10016
About this study
This is an investigator-initiated study comparing two types of FDA-approved anti-depressants, Escitalopram and Venlafaxine, to placebo, in order to determine if these medications have positive effects on cognition and memory in those who are between the ages of 50 to 89 years old, who are cognitively normal, and who have subjective memory concerns. Research has shown that those who are cognitively normal but report subjective cognitive impairment are more likely to progress to mild cognitive impairment and Alzheimer's disease in the future. Anti-depressants such as Escitalopram and Venlafaxine have been shown to stimulate production of neurons in memory-sensitive areas such as the hippocampus. Therefore, the investigator is researching whether these drugs would help cognition in those with subjective cognitive impairment, and would help to prevent cognitive decline and eventual Alzheimer's disease.
- Conditions
- Alzheimer Disease
- Being tested
- Escitalopram Pill, Venlafaxine Pill, Placebo Oral Tablet
- Keywords
- Alzheimer's Disease, Depression, Escitalopram, Venlafaxine
- Medical subject headings
- Alzheimer Disease, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Escitalopram PillDrug
Also called Lexapro
Subjects randomized to group A will receive Lexapro (escitalopram), in an initial, baseline dosage of 5 mg daily.
Venlafaxine PillDrug
Also called Effexor XR
Subjects randomized to group B will receive Effexor XR (venlafaxine extended release capsules), in an initial baseline dosage of 37.5 mg daily.
Placebo Oral TabletDrug
Subjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline.
| Study group | Role | What they receive |
|---|---|---|
| Escitalopram | Active comparator | Escitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant. Receives: Drug: Escitalopram Pill |
| Venlafaxine | Active comparator | Venlafaxine is a norepinephrine, serotonin and dopamine reuptake inhibitor antidepressant.The specific form of venlafaxine which will be employed is Effexor XR (venlafaxine hydrochloride extended release capsules) Receives: Drug: Venlafaxine Pill |
| Placebo | Placebo comparator | Subjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Z-score for the hippocampal region of interest in the theta band
responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.
Measured: 24 Months
Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;
Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.
Measured: 24 Months
Probability of deterioration from logistic regression predictive of future decline;
Measured: 24 Months
Z-score coherence (synchrony) between right central and parietal regions across all bands;
Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.
Measured: 24 Months
Mean frequency across the total EEG brain spectrum.
Measured: 24 Months
Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.
Measured: 24 Months
Secondary outcomes (3)
Brief Cognitive Rating Scale Axes I to V total scores
Measured: 24 Months
The Mini-Mental State Examination (MMSE) total scores
30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia.
Measured: 24 Months
MAC-Q total score
brief index of memory complaint.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start18 Jun 2009
- Primary completion25 Sep 2019
- Study completion25 Sep 2019
Why it stopped: Insufficient Enrollment
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 NYU Langone HealthThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Barry Reisberg, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03274817
- Sponsor's protocol ID
- 09-0228
- Status last verified
- May 2020
- First submitted
- 5 Sep 2017
- Last updated
- 2 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol
- ClinicalTrials.gov ID
- NCT03274817
- Acronym / sponsor ID
- 09-0228
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, Depression, Escitalopram, Venlafaxine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient Enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 18 Jun 2009 (actual)
- Primary completion
- 25 Sep 2019 (actual)
- Study completion
- 25 Sep 2019 (actual)
- First posted
- 7 Sep 2017 (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.
This is an investigator-initiated study comparing two types of FDA-approved anti-depressants, Escitalopram and Venlafaxine, to placebo, in order to determine if these medications have positive effects on cognition and memory in those who are between the ages of 50 to 89 years old, who are cognitively normal, and who have subjective memory concerns. Research has shown that those who are cognitively normal but report subjective cognitive impairment are more likely to progress to mild cognitive impairment and Alzheimer's disease in the future. Anti-depressants such as Escitalopram and Venlafaxine have been shown to stimulate production of neurons in memory-sensitive areas such as the hippocampus. Therefore, the investigator is researching whether these drugs would help cognition in those with subjective cognitive impairment, and would help to prevent cognitive decline and eventual Alzheimer's disease.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Escitalopram | Active comparator | Drug: Escitalopram PillEscitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant. |
| Venlafaxine | Active comparator | Drug: Venlafaxine PillVenlafaxine is a norepinephrine, serotonin and dopamine reuptake inhibitor antidepressant.The specific form of venlafaxine which will be employed is Effexor XR (venlafaxine hydrochloride extended release capsules) |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletSubjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline. |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects must have subjective cognitive impairment (SCI) and be free of objective evidence of cognitive impairment. Operationally, this will be defined as subjects with Global Deterioration Scale (GDS) score of stage 2.4
- Subjects must be between 60 and 80 years of age.
- Subjects must have a knowledgeable informant (study partner) who can accompany them to the evaluations, or, when necessary, be available for telephone contact.
- Subjects must be otherwise healthy and fulfill all of the inclusion criteria for participation in the NYU ADC. Exclusion criteria are enumerated below.
- Subjects must be in a position to comply with all of the study procedures described herein.
Key exclusion criteria (21 listed)
- Subjects who have normal brain aging, who are free of subjective cognitive impairment (SCI), and are therefore categorized at GDS stage 1, will be excluded.
- Subjects with MCI or dementia and are therefore categorized as being at GDS stage 3 or greater, will be excluded.
- Subjects with a mini mental status examination (MMSE) score61 of ≤ 27 will be excluded.
- Subjects with a Hamilton Depression Scale (HDS) score ≥ 16,62 signifying the presence of notable depressive symptomatology which warrants treatment, will be excluded.
- Subjects with a primary diagnosis of depression or with a major depression diagnosis will 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 |
|---|---|---|
| Escitalopram PillAlso: LexaproSubjects randomized to group A will receive Lexapro (escitalopram), in an initial, baseline dosage of 5 mg daily. | Drug | Escitalopram |
| Venlafaxine PillAlso: Effexor XRSubjects randomized to group B will receive Effexor XR (venlafaxine extended release capsules), in an initial baseline dosage of 37.5 mg daily. | Drug | Venlafaxine |
| Placebo Oral TabletSubjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline. | Drug | Placebo |
Primary outcome
Z-score for the hippocampal region of interest in the theta band
Time frame: 24 Months
responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.
Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;
Time frame: 24 Months
Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.
Probability of deterioration from logistic regression predictive of future decline;
Time frame: 24 Months
Z-score coherence (synchrony) between right central and parietal regions across all bands;
Time frame: 24 Months
Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.
Mean frequency across the total EEG brain spectrum.
Time frame: 24 Months
Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.
Time frame: 24 Months
3 secondary outcomes
Brief Cognitive Rating Scale Axes I to V total scores
Time frame: 24 Months
The Mini-Mental State Examination (MMSE) total scores
Time frame: 24 Months
MAC-Q total score
Time frame: 24 Months
Results and safety
The study was stopped early (reason given: Insufficient Enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Individual participant dataSharing planned: Undecided
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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.
Barry Reisberg principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Escitalopram Pill and Venlafaxine Pill in people with Alzheimer Disease, run by NYU Langone Health at 1 site 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 8 inclusion and 21 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: stopped early, as of the sponsor's last update on 2 Jun 2020. 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 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insufficient Enrollment). Results are not available in the source record.
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?
Z-score for the hippocampal region of interest in the theta band (time frame: 24 Months). The study lists 6 primary outcomes in all. 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 2 Jun 2020.