Mild Cognitive ImpairmentPhase 4NCT01845636
Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
A Phase 4 study testing Donepezil and Atropine in people with Mild Cognitive Impairment, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Odor identification deficits, which are a result of early Alzheimer's Disease (AD) pathology in the olfactory bulb and tract as well as olfactory projection areas in the medial temporal lobe (entorhinal and piriform cortex and hippocampus), lateral and central orbitofrontal cortex and several other regions, occur in… Read more about this study
- Who is it for?
- Ages 55 to 95 years
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Donepezil and Atropine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Mar 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
- Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:
- subjective memory complaints (ii) Wechsler Memory Scale-R Logical Memory combined Story A + B immediate recall score or combined Story A + B delayed recall score or Free and Cued Selective Reminding Test immediate recall or delayed recall score greater than 1.5 Standard Deviation (SD) below norms or Selective Reminding Test immediate recall or delayed recall score greater than 1.5 SD below norms iii) no functional impairment consistent with dementia
- Folstein Mini Mental State (MMSE) score ≥ 23 out of 30
- Clinical Dementia Rating (CDR) of 0.5 (questionable dementia)
- Availability of informant
Who cannot join
- Meets Criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) criteria or probable Alzheimer's disease
- Meets DSM IV criteria for:
- (i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
- Current untreated major depression or suicidality
- Parkinson's disease, Lewy body disease, multiple sclerosis, central nervous system infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
- Mental Retardation
Show all 12Show fewer
- Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.
- Patients receiving cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine will be excluded.
- Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.
- Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.
- Medications with anticholinergic effects that have been shown to adversely impact cognition will not be permitted. Benzodiazepines in lorazepam equivalents greater than or equal to 2 mg daily and narcotics will also not be permitted.
- Exclusion criterion for olfaction: history of anosmia due to any cause (e.g. traumatic or congenital) verified by UPSIT score of <11 out of 40; head trauma with loss of consciousness; nasal sinus disease, current upper respiratory infection; severe allergies to odors; current smoker > 1 pack daily.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Olfactory Deficits in Mild Cognitive Impairment as a Predictor of Improved Cognition on Donepezil
Odor identification deficits, which are a result of early Alzheimer's Disease (AD) pathology in the olfactory bulb and tract as well as olfactory projection areas in the medial temporal lobe (entorhinal and piriform cortex and hippocampus), lateral and central orbitofrontal cortex and several other regions, occur in AD and strongly predict mild cognitive impairment (MCI) conversion to AD. Our pilot data, along with converging findings in the literature, suggests that odor identification deficits, both incremental change over time and change in response to an anticholinergic challenge, may be clinically simple, relatively inexpensive, predictors of cognitive improvement with acetylcholinesterase inhibitor (ACheI) treatment with potential clinical implications for predicting improvement and monitoring ACheI therapy.
Read the detailed description
In this clinical trial, the investigators will evaluate, treat and follow a broad sample of 60 adult patients with amnestic MCI at New York State Psychiatric Institute/Columbia University Medical Center. Recruitment will be from clinics and/or advertisements. In the protocol, all 60 amnestic MCI patients will receive baseline memory and olfactory assessments and begin treatment with donepezil. Patients will be followed for a total of 1 year. During this time, patients will be monitored closely by the study physician and will receive memory and olfactory assessments at weeks 8, 26, and 52. In addition, an olfactory challenge test will be done at baseline.
This project will be of value in the selection of patients with mild cognitive impairment for treatment based on the evaluation of olfaction tests to predict response to donepezil and other ACheI. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Donepezil, Atropine
- Keywords
- Olfaction, Donepezil, Alzheimer's Disease, Mild Cognitive Impairment, Memory
- Medical subject headings
- Cognitive Dysfunction, Anosmia, Alzheimer Disease
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 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease.
AtropineDrug
Also called Atropine sulfate ophthalmic solution 1%
A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil Treatment & Atropine Challenge | Experimental | Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (UPSIT) immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks. Receives: Drug: Donepezil; Drug: Atropine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Selective Reminding Test (SRT)
The Selective Reminding Test (SRT) is a 12-item test of verbal learning and memory. To administer, the researcher will read aloud a list of 12 words. The participant repeats each word aloud to ensure that the word was heard correctly. Immediately following the reading of all 12 words, the participant is asked to recall as many words as possible within the one minute time limit. The participant is then reminded of the words they did not say and asked to recall the list again. This process is repeated for 6 trials. The total immediate recall is the total number of words recalled by the participant from all 6 trials. This is the number that is reported. Lower scores indicate fewer words recalled and a poorer performance.
Measured: Week 0, Week 8, Week 26, Week 52
Secondary outcomes (4)
Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
The modified Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation. The ADAS-Cog is not a timed test and the participant's score does not depend on how rapidly the test is completed. The ADAS-Cog total score is based on the total number of errors made in the test by the participant. Therefore, a lower total score indicates a higher cognitive performance. The total score ranges from 0 to 95 and is determined by summing the errors from 12 subscales. The total score, indicating number of errors made, is the number that is reported at each timeframe.
Measured: Week 0, Week 8, Week 26, Week 52
Pfeffer Functional Activities Questionnaire (FAQ)
FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning. The assessment is completed by a study informant - typically a caregiver able to report best on the patient's current ability. The instrument assesses the patient's current ability, at the point of testing and through the past month, in these various domains. The total score is described as the cumulative scores of each item, ranging from "0 - No help needed" to "3 - No, unable to do." More impairment is indicated by higher scores. The reported total score range is from 0 (no impairment score) to 30 (maximum impairment score).
Measured: Week 0, Week 4, Week 8, Week 26, Week 52
Measurement of Everyday Cognition (Ecog)
This instrument has 40 items, takes 20 minutes to administer, and focuses on functional correlates of cognitive deficits. This assessment asks the study informant to rate the participant's ability to perform certain tasks with the domains of Memory, Language, Visual-spatial and Perceptual Abilities, Executive Functioning: Planning, Executive Functioning: Organization, and Executive Functioning: Divided Attention. The informant is asked to compare functioning from 10 years prior to the time of testing. The Everyday Cognition measure uses the sum score of all of the subscales, and the items are reverse coded (i.e., 1= "Better or no change", 2="Questionable/occasionally worse", 3="Consistently a little worse", 4="Consistently much worse"), meaning that lower scores are better. Reported total scores range from 39 (Better or no change) to 156 (Consistently much worse).
Measured: Week 0, Week 4, Week 8, Week 26, Week 52
Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
The CIBIC-plus is a well-validated, reliable and widely used measure (range 1-7) of global improvement used in AD and MCI trials. This is a measure of change based on clinician impression.
Measured: Week 8, Week 26, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startAug 2012
- Primary completionMar 2016
- Study completionMar 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.
- Other trials for Mild Cognitive ImpairmentStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Davangere P. Devanand, New York State Psychiatric Institute
- Investigators
- Davangere Devanand, M.D., Principal investigator, Columbia UniversityGregory Pelton, M.D., Study director, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01845636
- Sponsor's protocol ID
- 6577
- Other IDs
- W81XWH-12-0142
- Status last verified
- Jun 2018
- First submitted
- 26 Apr 2013
- Last updated
- 9 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Olfactory Deficits in Mild Cognitive Impairment as a Predictor of Improved Cognition on Donepezil
- ClinicalTrials.gov ID
- NCT01845636
- Acronym / sponsor ID
- 6577
- Conditions
- Mild Cognitive Impairment
- Keywords
- Olfaction, Donepezil, Alzheimer's Disease, Mild Cognitive Impairment, Memory
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Aug 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Posted 13 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Odor identification deficits, which are a result of early Alzheimer's Disease (AD) pathology in the olfactory bulb and tract as well as olfactory projection areas in the medial temporal lobe (entorhinal and piriform cortex and hippocampus), lateral and central orbitofrontal cortex and several other regions, occur in AD and strongly predict mild cognitive impairment (MCI) conversion to AD. Our pilot data, along with converging findings in the literature, suggests that odor identification deficits, both incremental change over time and change in response to an anticholinergic challenge, may be clinically simple, relatively inexpensive, predictors of cognitive improvement with acetylcholinesterase inhibitor (ACheI) treatment with potential clinical implications for predicting improvement and monitoring ACheI therapy.
Detailed description
In this clinical trial, the investigators will evaluate, treat and follow a broad sample of 60 adult patients with amnestic MCI at New York State Psychiatric Institute/Columbia University Medical Center. Recruitment will be from clinics and/or advertisements. In the protocol, all 60 amnestic MCI patients will receive baseline memory and olfactory assessments and begin treatment with donepezil. Patients will be followed for a total of 1 year. During this time, patients will be monitored closely by the study physician and will receive memory and olfactory assessments at weeks 8, 26, and 52. In addition, an olfactory challenge test will be done at baseline.
This project will be of value in the selection of patients with mild cognitive impairment for treatment based on the evaluation of olfaction tests to predict response to donepezil and other ACheI. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Donepezil Treatment & Atropine Challenge | Experimental | Drug: Donepezil, Drug: AtropineAtropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (UPSIT) immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks. |
Who may qualify
- Ages
- 55 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Of either sex, age 55-95 years old
- Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:
- Folstein Mini Mental State (MMSE) score ≥ 23 out of 30
- Clinical Dementia Rating (CDR) of 0.5 (questionable dementia)
- Availability of informant
Key exclusion criteria (12 listed)
- Meets Criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) criteria or probable Alzheimer's disease
- Meets DSM IV criteria for:
- (i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
- Current untreated major depression or suicidality
- Parkinson's disease, Lewy body disease, multiple sclerosis, central nervous system infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
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 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. | Drug | Donepezil Treatment & Atropine Challenge |
| AtropineAlso: Atropine sulfate ophthalmic solution 1%A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians. | Drug | Donepezil Treatment & Atropine Challenge |
Primary outcome
Selective Reminding Test (SRT)
Time frame: Week 0, Week 8, Week 26, Week 52
The Selective Reminding Test (SRT) is a 12-item test of verbal learning and memory. To administer, the researcher will read aloud a list of 12 words. The participant repeats each word aloud to ensure that the word was heard correctly. Immediately following the reading of all 12 words, the participant is asked to recall as many words as possible within the one minute time limit. The participant is then reminded of the words they did not say and asked to recall the list again. This process is repeated for 6 trials. The total immediate recall is the total number of words recalled by the participant from all 6 trials. This is the number that is reported. Lower scores indicate fewer words recalled and a poorer performance.
4 secondary outcomes
Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Time frame: Week 0, Week 8, Week 26, Week 52
Pfeffer Functional Activities Questionnaire (FAQ)
Time frame: Week 0, Week 4, Week 8, Week 26, Week 52
Measurement of Everyday Cognition (Ecog)
Time frame: Week 0, Week 4, Week 8, Week 26, Week 52
Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Time frame: Week 8, Week 26, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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, M.D. principal investigator
Columbia University
Gregory Pelton, M.D. study director
Columbia University
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 Donepezil and Atropine in people with Mild Cognitive Impairment, run by New York State Psychiatric Institute 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 6 inclusion and 12 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 9 Jul 2018. 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. 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 13 Mar 2018). 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) (time frame: Week 0, Week 8, Week 26, Week 52). 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 9 Jul 2018.