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Trial record 1 of 1 for:    NCT02206620
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Effects of Cholinergic Augmentation on Measures of Balance and Gait

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ClinicalTrials.gov Identifier: NCT02206620
Recruitment Status : Completed
First Posted : August 1, 2014
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
John G. Nutt, Oregon Health and Science University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Intervention Drug: Donepezil
Enrollment 49
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Donepezil, Then Placebo Placebo, Then Donepezil
Hide Arm/Group Description Donepezil 5 mg per day for weeks 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo. Placebo (identical appearing capsules), two capsules per day for 2 weeks and four capsules per day for the following 2 weeks. Placebo (identical appearing capsules), two capsules per day for weeks 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks. Donepezil 5 mg per day for 2 weeks, then 10 mg/day for the following 2 weeks.
Period Title: Phase I - First Intervention (6 Weeks)
Started 22 27
Completed 21 26
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             1             1
Period Title: Washout (6 Weeks)
Started 21 26
Completed 21 26
Not Completed 0 0
Period Title: Phase II - Second Intervention (6 Weeks)
Started 21 26
Completed 21 24
Not Completed 0 2
Reason Not Completed
Withdrawal by Subject             0             2
Arm/Group Title All Study Participants
Hide Arm/Group Description Donepezil was taken for 3 weeks at 5mg/day (1 tablet/day) and then increased to 10mg/day (2 tablets/day) for another 3 weeks. The same was done for the placebo (1 tablet for the first 3 weeks, then 2 tablets for the following 3 weeks). There was a washout period of 6 weeks between the interventions. Participants were randomized to start with donepezil or placebo.
Overall Number of Baseline Participants 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants
69  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants
Female
14
  28.6%
Male
35
  71.4%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Disease Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants
7  (5)
MoCA   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 49 participants
26  (3)
[1]
Measure Description: Montreal Cognitive Assessment: overall cognition. Scale from 0 to 30. 30 represents intact cognitive status
MDS-UPDRS Part III   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 49 participants
43  (12)
[1]
Measure Description: Unified Parkinson's Disease Rating Scale (UPDRS), Movement Disorders Society (MDS) revised. Participants are rated on a variety of motor functions in a series of subscales. Subscale scores range from 0 to 4. The sub scales are summed to get the total score. The total score minimum score is 0 and the maximum score is 132. Higher values represent further disease progression.
1.Primary Outcome
Title Delta Medio-lateral Postural Sway Range (Foam)
Hide Description Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
Time Frame Six weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:

Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.

Donepezil

Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.

Donepezil

Overall Number of Participants Analyzed 49 49
Mean (Standard Deviation)
Unit of Measure: m/s^2
0.007  (0.045) -0.004  (0.028)
2.Primary Outcome
Title Delta of the Variability of Stride Time While Walking
Hide Description Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
Time Frame Six weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Variability of stride time was calculated from the stride time time-series as the coefficient of variation (CV, 100 multiplied by the SD of the stride times divided by the mean of each subject's stride times)
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.
Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.
Overall Number of Participants Analyzed 49 49
Mean (Standard Deviation)
Unit of Measure: percentage of gait cycle time
-0.32  (4.07) -0.038  (3.98)
3.Secondary Outcome
Title Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity
Hide Description Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).
Time Frame Six weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The average and standard deviation (SD) of the SAI at the end of each treatment is reported
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.
Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.
Overall Number of Participants Analyzed 49 49
Mean (Standard Deviation)
Unit of Measure: percentage of the unconditioned MEP
72.5  (26.9) 74.3  (23.8)
4.Secondary Outcome
Title Attention Network Test
Hide Description

Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.

The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).

Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials − mean RT DC trials; for the orienting network efficiency: mean RT CC trials − mean RT SC trials; and for the executive network efficiency: mean RT I trials − mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.

Time Frame Six weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.
Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.
Overall Number of Participants Analyzed 49 49
Mean (Standard Deviation)
Unit of Measure: ms
-19.5  (16.3) -5.1  (5.9)
Time Frame Adverse Events were collected through study completion, an average of 18 weeks.
Adverse Event Reporting Description

Adverse Events were systematically collected by phone call every week. Study clinicians recorded adverse events and reported to the IRB unexpected or serious adverse events. An independent neurologist reviewed the reported adverse events each six months and made recommendations to the trial leadership as well as the IRB about advisability of continuation of the trial.

The adverse events are reported below per intervention for each Arm/Group of the study.

 
Arm/Group Title Donepezil, Then Placebo (Phase I) Placebo, Then Donepezil (Phase I) Donepezil, Then Placebo (Washout) Placebo, Then Donepezil (Washout) Donepezil, Then Placebo (Phase II) Placebo, Then Donepezil (Phase II)
Hide Arm/Group Description Participants took a donepezil 5mg tablet each day for 3 weeks, then increased the dose to 10mg (2 tablets each day) for 3 weeks. (This was followed by 6 weeks of a washout period and then taking the placebo in the same format -- 3 weeks of one tablet, followed by 3 weeks of 2 tablets to replicate the dosage increase.) Participants took the placebo at one tablet each day for 3 weeks, then increased the dosage to 2 tablets each day for 3 weeks. (This was followed by 6 weeks of a washout period and then taking donepezil in the same format -- donepezil 5mg tablet each day for 3 weeks, followed by 3 weeks of an increased dose of 10mg (2 tablets each day).) There were 6 weeks of a washout period after participants had taken donepezil for 6 weeks. There were 6 weeks of a washout period after participants had taken the placebo for 6 weeks. After the washout period, participants took the placebo in the same format as the donepezil -- 3 weeks of one tablet, followed by 3 weeks of 2 tablets to replicate the dosage increase. Then participants took donepezil in the same formats the placebo -- the donepezil 5mg tablet each day for 3 weeks, followed by 3 weeks of an increased dose of 10mg (2 tablets each day).
All-Cause Mortality
Donepezil, Then Placebo (Phase I) Placebo, Then Donepezil (Phase I) Donepezil, Then Placebo (Washout) Placebo, Then Donepezil (Washout) Donepezil, Then Placebo (Phase II) Placebo, Then Donepezil (Phase II)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/27 (0.00%)      0/21 (0.00%)      0/26 (0.00%)      0/21 (0.00%)      0/26 (0.00%)    
Hide Serious Adverse Events
Donepezil, Then Placebo (Phase I) Placebo, Then Donepezil (Phase I) Donepezil, Then Placebo (Washout) Placebo, Then Donepezil (Washout) Donepezil, Then Placebo (Phase II) Placebo, Then Donepezil (Phase II)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/22 (0.00%)      0/27 (0.00%)      0/21 (0.00%)      1/26 (3.85%)      0/21 (0.00%)      0/26 (0.00%)    
Respiratory, thoracic and mediastinal disorders             
Pulmonary Embolus *  0/22 (0.00%)  0 0/27 (0.00%)  0 0/21 (0.00%)  0 1/26 (3.85%)  1 0/21 (0.00%)  0 0/26 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Donepezil, Then Placebo (Phase I) Placebo, Then Donepezil (Phase I) Donepezil, Then Placebo (Washout) Placebo, Then Donepezil (Washout) Donepezil, Then Placebo (Phase II) Placebo, Then Donepezil (Phase II)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/22 (81.82%)      18/27 (66.67%)      5/21 (23.81%)      8/26 (30.77%)      4/21 (19.05%)      26/26 (100.00%)    
Gastrointestinal disorders             
Anorexia   0/22 (0.00%)  1/27 (3.70%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  2/26 (7.69%) 
Nausea   6/22 (27.27%)  2/27 (7.41%)  0/21 (0.00%)  1/26 (3.85%)  2/21 (9.52%)  8/26 (30.77%) 
Diarrhea   2/22 (9.09%)  1/27 (3.70%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  3/26 (11.54%) 
Constipation   1/22 (4.55%)  2/27 (7.41%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  2/26 (7.69%) 
Abdominal Pain   1/22 (4.55%)  1/27 (3.70%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  1/26 (3.85%) 
General disorders             
Insomnia   3/22 (13.64%)  5/27 (18.52%)  1/21 (4.76%)  1/26 (3.85%)  1/21 (4.76%)  6/26 (23.08%) 
Vivid Dreams   2/22 (9.09%)  2/27 (7.41%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  2/26 (7.69%) 
Light Headedness   3/22 (13.64%)  4/27 (14.81%)  0/21 (0.00%)  2/26 (7.69%)  1/21 (4.76%)  3/26 (11.54%) 
Headache   2/22 (9.09%)  0/27 (0.00%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  0/26 (0.00%) 
Hallucinations   2/22 (9.09%)  0/27 (0.00%)  1/21 (4.76%)  1/26 (3.85%)  1/21 (4.76%)  1/26 (3.85%) 
Memory Disturbances   1/22 (4.55%)  2/27 (7.41%)  0/21 (0.00%)  1/26 (3.85%)  0/21 (0.00%)  0/26 (0.00%) 
Increased Saliva   1/22 (4.55%)  1/27 (3.70%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  0/26 (0.00%) 
Decreased Saliva   0/22 (0.00%)  2/27 (7.41%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  0/26 (0.00%) 
Other  [1]  4/22 (18.18%)  5/27 (18.52%)  2/21 (9.52%)  2/26 (7.69%)  1/21 (4.76%)  7/26 (26.92%) 
Musculoskeletal and connective tissue disorders             
Fatigue   4/22 (18.18%)  1/27 (3.70%)  0/21 (0.00%)  0/26 (0.00%)  2/21 (9.52%)  3/26 (11.54%) 
Muscle Cramps   3/22 (13.64%)  3/27 (11.11%)  2/21 (9.52%)  0/26 (0.00%)  1/21 (4.76%)  5/26 (19.23%) 
Renal and urinary disorders             
Urinary Frequency   2/22 (9.09%)  4/27 (14.81%)  0/21 (0.00%)  0/26 (0.00%)  0/21 (0.00%)  4/26 (15.38%) 
Respiratory, thoracic and mediastinal disorders             
Upper Respiratory Tract Infection   4/22 (18.18%)  3/27 (11.11%)  0/21 (0.00%)  1/26 (3.85%)  0/21 (0.00%)  0/26 (0.00%) 
Indicates events were collected by systematic assessment
[1]
other adverse events consisting of Irregular Heartbeat, Pain, Weakness, Anxiety, Excessive Sweating, Trouble Swallowing, Infection, Rash, Food Poisoning, Impulse Control, Increased Freezing of Gait, etc
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Martina Mancini
Organization: Oregon Health & Science University
Phone: 5034182602
EMail: mancinim@ohsu.edu
Layout table for additonal information
Responsible Party: John G. Nutt, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT02206620    
Other Study ID Numbers: 9437
First Submitted: July 29, 2014
First Posted: August 1, 2014
Results First Submitted: March 13, 2019
Results First Posted: November 14, 2019
Last Update Posted: November 14, 2019