Trial Outcomes & Findings for Combination Treatment Study for Memory Impairment and Depression (NCT NCT01658228)
NCT ID: NCT01658228
Last Updated: 2017-10-17
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
86 participants
Primary outcome timeframe
Week 16
Results posted on
2017-10-17
Participant Flow
Patients were recruited from clinics and/or advertisements.
86 subjects were enrolled in the open treatment phase of the study and then 61 subjects were randomized at 16 weeks to the add-on donepezil/placebo treatment groups.
Participant milestones
| Measure |
Donepezil Treatment Group
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.
|
Placebo Treatment Group
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.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
31
|
|
Overall Study
COMPLETED
|
23
|
23
|
|
Overall Study
NOT COMPLETED
|
7
|
8
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination Treatment Study for Memory Impairment and Depression
Baseline characteristics by cohort
| Measure |
Donepezil Treatment Group
n=30 Participants
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.
Donepezil: 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.
|
Placebo Treatment Group
n=31 Participants
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.
Placebo: 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.
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
18 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Age, Continuous
|
67.1 Years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
72.4 Years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
69.8 Years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 16The 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.
Outcome measures
| Measure |
Donepezil Treatment Group
n=30 Participants
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.
|
Placebo Treatment Group
n=31 Participants
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.
|
|---|---|---|
|
Selective Reminding Test (SRT) Total Recall
|
45.6 Words
Standard Deviation 11.2
|
46.6 Words
Standard Deviation 11.3
|
PRIMARY outcome
Timeframe: Week 16The 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.
Outcome measures
| Measure |
Donepezil Treatment Group
n=30 Participants
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.
|
Placebo Treatment Group
n=31 Participants
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.
|
|---|---|---|
|
Selective Reminding Test (SRT) Delayed Recall
|
7.4 Words
Standard Deviation 3
|
7.4 Words
Standard Deviation 2.8
|
SECONDARY outcome
Timeframe: Week 16The 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.
Outcome measures
| Measure |
Donepezil Treatment Group
n=30 Participants
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.
|
Placebo Treatment Group
n=31 Participants
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.
|
|---|---|---|
|
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
|
13.2 number of errors on a scale from 0-85
Standard Deviation 6.6
|
13.9 number of errors on a scale from 0-85
Standard Deviation 7.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Parts A and B are composed of 25 circles. Patients are asked to scan the entire page and identify the next number or letter in a sequence.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0), Week 16, Week 40, Week 64, Week 78Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 2Using a standard protocol, DNA is amplified by the polymerase chase reaction (PCR). The genotypes are determined blind to subject status (patient or control) by the sizes of DNA fragments present.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Screen (Week 0)The subject will "scratch and sniff" 40 common odorants embedded in microcapsules on a separate page. The subject will choose the answer from a 4-item multiple choice list. Scores will range from 0-40.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Within 1 month of Screen Visit (Week 0)Images will be obtained using a GE Signa 3 Tesla whole body scanner. T1-weighted sagittal fspgr and T2 FLAIR are the pulse sequences used in order to obtain the MRI images.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0 ScreeningOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0 ScreeningOutcome measures
Outcome data not reported
Adverse Events
Donepezil Treatment Group
Serious events: 8 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo Treatment Group
Serious events: 7 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Donepezil Treatment Group
n=30 participants at risk
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.
|
Placebo Treatment Group
n=31 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Cardiac Stents
|
3.3%
1/30
|
0.00%
0/31
|
|
Injury, poisoning and procedural complications
Fall
|
3.3%
1/30
|
6.5%
2/31
|
|
Immune system disorders
Allergic Reaction
|
3.3%
1/30
|
0.00%
0/31
|
|
Cardiac disorders
Atrial Flutter
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Chest Pain
|
3.3%
1/30
|
3.2%
1/31
|
|
General disorders
Leg Pain
|
0.00%
0/30
|
3.2%
1/31
|
|
Psychiatric disorders
Panic Attack
|
0.00%
0/30
|
3.2%
1/31
|
|
Psychiatric disorders
Fugue State
|
0.00%
0/30
|
3.2%
1/31
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/30
|
3.2%
1/31
|
|
Renal and urinary disorders
Kidney Stones
|
0.00%
0/30
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Polymyalgia Rheumatica
|
0.00%
0/30
|
3.2%
1/31
|
|
General disorders
Colorectal Cancer
|
3.3%
1/30
|
0.00%
0/31
|
|
Renal and urinary disorders
Perirectal Abscess
|
3.3%
1/30
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Right Upper Rotator Cuff Repair
|
3.3%
1/30
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Biceps Tendinopathy
|
3.3%
1/30
|
0.00%
0/31
|
|
Injury, poisoning and procedural complications
Accidental Injury to Left Arm
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Stroke
|
0.00%
0/30
|
3.2%
1/31
|
|
Congenital, familial and genetic disorders
Parkinson's Disease
|
0.00%
0/30
|
3.2%
1/31
|
Other adverse events
| Measure |
Donepezil Treatment Group
n=30 participants at risk
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.
|
Placebo Treatment Group
n=31 participants at risk
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.
|
|---|---|---|
|
Metabolism and nutrition disorders
Diarrhea
|
40.0%
12/30
|
19.4%
6/31
|
|
Metabolism and nutrition disorders
Headache/Dizziness
|
23.3%
7/30
|
16.1%
5/31
|
|
Metabolism and nutrition disorders
Upset Stomach
|
6.7%
2/30
|
6.5%
2/31
|
|
Psychiatric disorders
Nightmares
|
13.3%
4/30
|
6.5%
2/31
|
|
Cardiac disorders
High Blood Pressure
|
3.3%
1/30
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Fall
|
6.7%
2/30
|
16.1%
5/31
|
|
Injury, poisoning and procedural complications
Broken Knee
|
0.00%
0/30
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Broken 4th Finger
|
0.00%
0/30
|
3.2%
1/31
|
|
General disorders
Nasal Congestion
|
13.3%
4/30
|
0.00%
0/31
|
|
Infections and infestations
Upper Respiratory Infection
|
6.7%
2/30
|
3.2%
1/31
|
|
Infections and infestations
Pneumonia
|
3.3%
1/30
|
3.2%
1/31
|
|
Infections and infestations
Sinus Infection
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Cough
|
6.7%
2/30
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Restless Leg
|
3.3%
1/30
|
0.00%
0/31
|
|
Psychiatric disorders
Confusion
|
3.3%
1/30
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramps
|
10.0%
3/30
|
0.00%
0/31
|
|
General disorders
Dry Mouth
|
16.7%
5/30
|
6.5%
2/31
|
|
Infections and infestations
Ear Infection
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Sore Throat
|
3.3%
1/30
|
3.2%
1/31
|
|
General disorders
Pharyngitis
|
3.3%
1/30
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Knee Pain
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Fatigue/Insomnia
|
26.7%
8/30
|
16.1%
5/31
|
|
Metabolism and nutrition disorders
Vomiting
|
6.7%
2/30
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Constipation
|
3.3%
1/30
|
6.5%
2/31
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Shingles
|
3.3%
1/30
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Herniated Disk in Neck
|
3.3%
1/30
|
0.00%
0/31
|
|
Infections and infestations
Poison Ivy
|
3.3%
1/30
|
6.5%
2/31
|
|
Infections and infestations
Fungus on Toes
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Elevated Temperature
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Akathisia
|
3.3%
1/30
|
0.00%
0/31
|
|
Nervous system disorders
Unsteadiness
|
3.3%
1/30
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
GI Reflux
|
3.3%
1/30
|
0.00%
0/31
|
|
Nervous system disorders
Tremor
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Sweating
|
3.3%
1/30
|
3.2%
1/31
|
|
Renal and urinary disorders
UTI
|
6.7%
2/30
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Nausea
|
10.0%
3/30
|
3.2%
1/31
|
|
General disorders
Hot Flashes
|
3.3%
1/30
|
0.00%
0/31
|
|
Musculoskeletal and connective tissue disorders
Hip Pain
|
3.3%
1/30
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Weight Loss
|
3.3%
1/30
|
0.00%
0/31
|
|
General disorders
Flu
|
3.3%
1/30
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Bloating
|
3.3%
1/30
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/30
|
3.2%
1/31
|
|
Infections and infestations
Vaginal Infection
|
0.00%
0/30
|
3.2%
1/31
|
|
General disorders
Bruxism
|
0.00%
0/30
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Knee Inflammation
|
0.00%
0/30
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Increased Weight
|
0.00%
0/30
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Increased Appetite
|
0.00%
0/30
|
3.2%
1/31
|
|
General disorders
Flatulence
|
0.00%
0/30
|
3.2%
1/31
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/30
|
3.2%
1/31
|
|
Nervous system disorders
Lower extremity neuropathy
|
0.00%
0/30
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Right Ankle Fracture
|
0.00%
0/30
|
3.2%
1/31
|
Additional Information
Dr. Davangere Devanand
New York State Psychiatric Institute
Phone: 646-774-8658
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place