Trial Outcomes & Findings for Memantine for Treatment of Cognitive Impairment in Patients With Parkinson's Disease and Dementia (NCT NCT00294554)
NCT ID: NCT00294554
Last Updated: 2017-09-12
Results Overview
The DRS is comprised of: Attention (ATT, 8 items); Initiation-Perseveration (I-P, 11 items); Construction (CONST, 6 items); Conceptualization (CONCEPT, 6 items); and Memory (MEM, 5 items). For this study, only the memory subscore was used, with score possibilities ranging from 0-5, with 5 meaning memory was perfect, 0 being no ability to recall. A negative score indicates a decrease in memory from baseline to 24 weeks.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
20 participants
Primary outcome timeframe
change from baseline to 24 weeks
Results posted on
2017-09-12
Participant Flow
Men and women with idiopathic Parkinson's disease (PD) and dementia due to PD recruited from outpatient clinics at Johns Hopkins and outreach to the Baltimore-Washington community through the Johns Hopkins Morris K. Udall Parkinson's Disease Research Center. Recruitment period was 2006 to 2008.
Enrolled participants were excluded if screening assessment showed MMSE\>10 and Clinical Dementia Rating (CDR) scale score \>1, or diagnostic criteria for dementia with Lewy bodies or DSM-IV-TR substance abuse/dependence or major depressive episode, Hamilton Depression Rating Scale score\>17, or severe cardiac, vascular or renal disease.
Participant milestones
| Measure |
Active Memantine
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Active Memantine
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Memantine for Treatment of Cognitive Impairment in Patients With Parkinson's Disease and Dementia
Baseline characteristics by cohort
| Measure |
Active Memantine
n=10 Participants
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
n=10 Participants
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71.7 years
STANDARD_DEVIATION 7.3 • n=93 Participants
|
71.9 years
STANDARD_DEVIATION 7.5 • n=4 Participants
|
71.8 years
STANDARD_DEVIATION 7.4 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=93 Participants
|
10 participants
n=4 Participants
|
20 participants
n=27 Participants
|
|
Education
|
17.2 years
STANDARD_DEVIATION 4.5 • n=93 Participants
|
16.9 years
STANDARD_DEVIATION 3.0 • n=4 Participants
|
17.1 years
STANDARD_DEVIATION 3.7 • n=27 Participants
|
|
NART (Full Scale IQ)
|
108.0 units on a scale
STANDARD_DEVIATION 9.5 • n=93 Participants
|
102.7 units on a scale
STANDARD_DEVIATION 6.6 • n=4 Participants
|
105.5 units on a scale
STANDARD_DEVIATION 8.5 • n=27 Participants
|
PRIMARY outcome
Timeframe: change from baseline to 24 weeksThe DRS is comprised of: Attention (ATT, 8 items); Initiation-Perseveration (I-P, 11 items); Construction (CONST, 6 items); Conceptualization (CONCEPT, 6 items); and Memory (MEM, 5 items). For this study, only the memory subscore was used, with score possibilities ranging from 0-5, with 5 meaning memory was perfect, 0 being no ability to recall. A negative score indicates a decrease in memory from baseline to 24 weeks.
Outcome measures
| Measure |
Active Memantine
n=10 Participants
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
n=10 Participants
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
|---|---|---|
|
Change in Dementia Rating Scale (DRS) Memory Subscore
|
1.6 units on a scale
Interval -0.13 to 3.33
|
-1.4 units on a scale
Interval -3.19 to 0.39
|
PRIMARY outcome
Timeframe: 24 weeksCIBIC-Plus is based upon clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the patient and interview of informants. It takes into account a subject's overall function in the cognitive, behavioral and functional activity domains. Scoring is based on an interview with the caregiver and examination of the patient by an independent evaluator, without consulting other information such as cognitive test results. It requires the assessor to consider a number of cognitive, functional, and behavioral areas prior to providing an overall "global" assessment of clinical change. 7-point categorical scale that provides a single global rating of change from baseline.A score of 1 indicates marked improvement;and a score of 7, marked worsening.
Outcome measures
| Measure |
Active Memantine
n=10 Participants
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
n=10 Participants
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
|---|---|---|
|
CIBIC-Plus Score
Very Much Improved
|
1 Participants
|
0 Participants
|
|
CIBIC-Plus Score
Much Improved
|
5 Participants
|
2 Participants
|
|
CIBIC-Plus Score
Minimally Improved
|
2 Participants
|
1 Participants
|
|
CIBIC-Plus Score
No Change
|
0 Participants
|
3 Participants
|
|
CIBIC-Plus Score
Minimally Worse
|
2 Participants
|
2 Participants
|
|
CIBIC-Plus Score
Much Worse
|
0 Participants
|
2 Participants
|
|
CIBIC-Plus Score
Very Much Worse
|
0 Participants
|
0 Participants
|
Adverse Events
Active Memantine
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo Oral Tablet
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active Memantine
n=10 participants at risk
Memantine tablets, formulated in appearance to match the placebo comparator, were initiated at 5 mg daily and advanced by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Memantine: Active memantine and placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
Placebo Oral Tablet
n=10 participants at risk
Placebo tablets were formulated to match active 5mg memantine tablets. Dosing same as the active comparator with initiation at 5 mg daily and advancing by 5mg /week to 20 mg/week by week 4 with dosing at 10 mg bid over the remaining 20 weeks of the trial. Over the 6 month duration of the trial, dosage could be titrated downward in increments of 5 mg to a minimum dose of 5mg/day in the event of intolerance.
Placebo Oral Tablet: Placebo, taken by mouth, will be titrated from 5mg a day to 20mg a day over 4 weeks. The subject will remain on 20mg (10mg twice a day) through week 24 unless unable to tolerate. The dose will be decreased as needed.
|
|---|---|---|
|
Nervous system disorders
Incident Concentration Difficulties
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident Fatigue
|
20.0%
2/10 • Number of events 2 • 6 months
|
0.00%
0/10 • 6 months
|
|
General disorders
Incident Sleepiness
|
20.0%
2/10 • Number of events 2 • 6 months
|
0.00%
0/10 • 6 months
|
|
Psychiatric disorders
Incident Depression
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Psychiatric disorders
Incident Tension
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Increased Confusion
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Psychiatric disorders
Incident Hypomania
|
10.0%
1/10 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Psychiatric disorders
Incident Agitation
|
20.0%
2/10 • Number of events 2 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident Increased Sleep
|
30.0%
3/10 • Number of events 3 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident reduced Sleep
|
0.00%
0/10 • 6 months
|
40.0%
4/10 • Number of events 4 • 6 months
|
|
Nervous system disorders
Incident Increased Dreaming
|
30.0%
3/10 • Number of events 3 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Nervous system disorders
Incident Dystonia
|
20.0%
2/10 • Number of events 2 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Rigidity
|
10.0%
1/10 • Number of events 1 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Nervous system disorders
Incident Hypokinesia
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Hyperkinesia
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident tremor
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Akathisia
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Myoclonus
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Imbalance
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Paresthesias
|
10.0%
1/10 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Nervous system disorders
Incident Headache
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Nervous system disorders
Incident Ocular Accommodation disturbances
|
0.00%
0/10 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Gastrointestinal disorders
Incident Increased Salivatino
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Gastrointestinal disorders
Incident reduced Salivation
|
20.0%
2/10 • Number of events 2 • 6 months
|
0.00%
0/10 • 6 months
|
|
Gastrointestinal disorders
Incident Nausea/vomiting
|
0.00%
0/10 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Renal and urinary disorders
Incident Micturation Disturbances
|
20.0%
2/10 • Number of events 2 • 6 months
|
0.00%
0/10 • 6 months
|
|
Renal and urinary disorders
Incident Polyuria
|
20.0%
2/10 • Number of events 2 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Cardiac disorders
Incident Orthostatic Dizziness
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
Cardiac disorders
Incident tachycardia
|
10.0%
1/10 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
General disorders
Incident Increased Sweating
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident Shivering
|
10.0%
1/10 • Number of events 1 • 6 months
|
20.0%
2/10 • Number of events 2 • 6 months
|
|
Skin and subcutaneous tissue disorders
Incident Rash
|
10.0%
1/10 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Skin and subcutaneous tissue disorders
Incident Pruritus
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident Increased Sexual Desire
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
|
General disorders
Incident Diminished Sexual Desire
|
10.0%
1/10 • Number of events 1 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
Additional Information
Laura Marsh, MD
Johns Hopkins University School of Medicine
Phone: 713-794-8907
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place