← Trials/Trial dossier/NCT01951118

CompletedPhase 4Results posted

Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Lead sponsor

New York State Psychiatric Institute

Asset

Donepezil

Listed sites

Recruiting sites

Enrollment

121

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criterion

•MMSE ≥23

Primary endpoint

•Change Over Time in Selective Reminding Test (SRT) Scores

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Nih1R01AG041795

Org study ID6655

NCT IDNCT01951118

Timeline

Milestones

Study first posted2013-09-26estimated

Study start2013-10actual (month precision)

Primary completion2019-05actual (month precision)

Study completion2019-05actual (month precision)

Last update posted2020-07-13actual

Results first posted2020-07-13actual

Assets

Drug assets

Donepezil

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years

Maximum age95 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Study 1

Inclusion Criteria:

•Of either sex, age 55-95 years old

•Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:

(i) subjective memory complaints (ii) Wechsler Memory Scale-III 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

•Retains capacity to consent

Exclusion criteria

•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 less than or equal to 2 mg daily and narcotics will also not be permitted.

•Meets criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)

•Meets Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) 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

•Cystic Fibrosis

•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. Patients already receiving one of these medications at screening who undergo a 2-week washout before starting all study procedures will not 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.

•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.

•Exclusion criteria for atropine nasal spray: presence of nasal deformity or disease that makes it difficult to administer the nasal spray reliably. A patient who cannot complete the atropine nasal spray procedure can still participate in the rest of the study.

Study 2

Inclusion Criteria:

•Of either sex, age 55-95 years old

•Diagnosis of probable Alzheimer's disease (NINCDS-ADRDA criteria) and the diagnosis of "Probable AD dementia: core clinical diagnosis with amnestic or nonamnestic initial presentation".

•Folstein Mini Mental State (MMSE) score 18-27 out of 30

•Availability of informant

•Retains capacity to consent

Exclusion Criteria:

•Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.

•Meets DSM IV TR 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

•Cystic Fibrosis

•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.

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Memory

Executive function / language

Global cognition

Other (unclassified)

Function / daily living

Other clinical outcomes

Global cognition

4 endpoints

Secondary/protocol endpoint

Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)

Time frame:Week 0, Week 8, Week 26, Week 52

ADAS-Cog

event count, event

Secondary/registry result

Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)

Time frame:Week 0, Week 8, Week 26, Week 52

ADAS-Cog

event count, event

Posted result

Group	Value (mean), Errors	Standard deviation
MCI SampleWeek 0n=99 Participants	11.41	4.67
Week 8n=89 Participants	10.13	4.22
Week 26n=83 Participants	9.63	4.44
Week 52n=77 Participants	10.40	4.72
AD SampleWeek 0n=21 Participants	21.67	6.12
Week 8n=20 Participants	19.30	5.80
Week 26n=20 Participants	19.63	7.15
Week 52n=15 Participants	22.69	8.99

Other/protocol endpoint

Mini-Mental State Examination - MMSE

Time frame:Week 0, Week 26, Week 52

Mini-Mental State Examination (MMSE)

descriptive

Other_pre_specified/registry result

Mini-Mental State Examination - MMSE

Time frame:Week 0, Week 26, Week 52

Mini-Mental State Examination (MMSE)

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 0n=100 Participants	26.72	2.17
Week 26n=83 Participants	26.90	2.20
Week 52n=77 Participants	26.44	2.47
AD SampleWeek 0n=21 Participants	23.048	2.40
Week 26n=20 Participants	21.20	3.52
Week 52n=17 Participants	20.35	3.71

Memory

6 endpoints

Primary/protocol endpoint

Change Over Time in Selective Reminding Test (SRT) Scores

Time frame:Week 0, Week 8, Week 26, Week 52

event count, event

Primary/registry result

Change Over Time in Selective Reminding Test (SRT) Scores

Time frame:Week 0, Week 8, Week 26, Week 52

event count, event

Posted result

Group	Value (mean), Words	Standard deviation
MCI SampleWeek 0n=100 Participants	36.14	10.67
Week 8n=90 Participants	39.99	10.30
Week 26n=83 Participants	39.75	10.69
Week 52n=77 Participants	39.62	11.44
AD SampleWeek 0n=21 Participants	21.19	8.23
Week 8n=20 Participants	24.10	9.82
Week 26n=20 Participants	23.00	8.07
Week 52n=16 Participants	24.38	9.69

Secondary/protocol endpoint

Measurement of Everyday Cognition (Ecog)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Secondary/registry result

Measurement of Everyday Cognition (Ecog)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 0n=92 Participants	67.93	20.58
Week 8n=83 Participants	67.88	23.35
Week 26n=77 Participants	67.92	23.20
Week 52n=74 Participants	66.84	22.66
AD SampleWeek 0n=20 Participants	90.80	28.11
Week 8n=20 Participants	89.20	31.14
Week 26n=20 Participants	97.65	29.02
Week 52n=17 Participants	103.59	29.27

Other/protocol endpoint

Wechsler Memory Scale (WMS)-R Digit Span

Time frame:Week 0, Week 52.

descriptive

Other_pre_specified/registry result

Wechsler Memory Scale (WMS)-R Digit Span

Time frame:Week 0, Week 52.

descriptive

Executive function / language

6 endpoints

Other/protocol endpoint

Trail Making Test (Parts A and B)

Time frame:Week 0, Week 52

descriptive

Other/protocol endpoint

Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest

Time frame:Week 0, Week 52

descriptive

Other/protocol endpoint

Boston Naming Test (BNT)

Time frame:Week 0, Week 52

descriptive

Other_pre_specified/registry result

Trail Making Test (Parts A and B)

Time frame:Week 0, Week 52

descriptive

Other_pre_specified/registry result

Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest

Time frame:Week 0, Week 52

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 0n=99 Participants	36.83	13.72
Week 52n=76 Participants	37.24	12.17
AD SampleWeek 0n=19 Participants	25.47	9.27
Week 52n=16 Participants	21.06	11.66

Other_pre_specified/registry result

Boston Naming Test (BNT)

Time frame:Week 0, Week 52

descriptive

Function / daily living

2 endpoints

Secondary/protocol endpoint

Pfeffer Functional Activities Questionnaire (FAQ)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Secondary/registry result

Pfeffer Functional Activities Questionnaire (FAQ)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 0n=94 Participants	4.80	4.84
Week 8n=83 Participants	4.68	4.56
Week 26n=77 Participants	4.84	4.96
Week 52n=74 Participants	4.25	4.76
AD SampleWeek 0n=16 Participants	11.25	6.19
Week 8n=18 Participants	11.78	4.72
Week 26n=20 Participants	13.75	5.46
Week 52n=13 Participants	14.62	4.15

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

Clinician's Interview Based Impression (CIBIC-plus)

Time frame:Week 8, Week 26, Week 52

descriptive

Secondary/registry result

Clinician's Interview Based Impression (CIBIC-plus)

Time frame:Week 8, Week 26, Week 52

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 8n=89 Participants	3.34	0.74
Week 26n=82 Participants	3.15	0.86
Week 52n=76 Participants	3.11	1.17
AD SampleWeek 8n=20 Participants	3.55	0.69
Week 26n=20 Participants	3.75	0.64
Week 52n=16 Participants	4.38	0.96

Other (unclassified)

4 endpoints

Other/protocol endpoint/low confidence

Controlled Word Association (CFL)

Time frame:Week 0, Week 52

descriptive

Other/protocol endpoint/low confidence

Treatment Emergent Symptom Scale (TESS)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Other_pre_specified/registry result/low confidence

Controlled Word Association (CFL)

Time frame:Week 0, Week 52

descriptive

Other_pre_specified/registry result/low confidence

Treatment Emergent Symptom Scale (TESS)

Time frame:Week 0, Week 8, Week 26, Week 52

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
MCI SampleWeek 0n=98 Participants	2.57	2.62
Week 8n=88 Participants	1.61	1.90
Week 26n=77 Participants	1.42	1.86
Week 52n=74 Participants	1.28	2.11
AD SampleWeek 0n=18 Participants	1.89	2.05
Week 8n=17 Participants	1.53	1.37
Week 26n=20 Participants	1.20	1.47
Week 52n=16 Participants	1.69	2.33

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Devanand DP, Liu X, Chunga RE, Cohen H, Andrews H, Schofield PW, Stern Y, Huey ED, Choi J, Pelton GH. Odor Identification Impairment and Change with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment. J Alzheimers Dis. 2020;75(3):845-854. doi: 10.3233/JAD-200021.
PMID32333591via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.