Memantine for Treatment of Cognitive Impairment in Patients With Parkinson's Disease and Dementia
|Parkinson's Disease Cognitive Impairment Dementia||Drug: Memantine Drug: Placebo Oral Tablet|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Double-Blind Placebo-Controlled Trial of Memantine for Treatment of Cognitive Impairment in Patients With Parkinson's Disease and Dementia|
- Change in Dementia Rating Scale (DRS) Memory Subscore [ Time Frame: change from baseline to 24 weeks ]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.
- CIBIC-Plus Score [ Time Frame: 24 weeks ]CIBIC-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.
|Study Start Date:||April 2006|
|Study Completion Date:||December 2008|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 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.
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.
Other Name: Namenda
Placebo Comparator: 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.
Drug: 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.
Other Name: Placebo
This is a randomized, placebo-controlled, parallel, double-blind 24-week prospective study of memantine at the dosage range 5-20 mg/day in 20 outpatients with idiopathic PD and dementia secondary to PD. Using the dosage escalation regimen approved for Alzheimer disease, subjects will start memantine or comparable placebo at 5 mg daily and advance 5 mg/week to 20 mg /day by week 4, with dosing at 10 mg bid. Subjects will undergo 7 clinical visits over the 6-month trial (Screen, Baseline/Week 0, and Weeks 4, 8, 14, 20, and 24). The dosage can be titrated downward in increments of 5 mg to a minimum dose of 5 mg/day in the event memantine is not tolerated at the scheduled dosages. This broad dose range is being used because 1)a favorable cognitive response may be evident at lower doses of memantine than recommended for AD and 2)adverse effects could emerge when typical AD dosing recommendations are used, as has been observed when treating PD patients with cholinesterase inhibitors. Subjects will remain on a stable dose of memantine/placebo after Week 8, unless precluded by adverse events. Ten subjects will be assigned to each treatment group. Randomization will be stratified according to whether subjects are taking a concomitant cholinesterase inhibitor. This will enable secondary group comparisons of treatment groups. Results from this initial small study will be used to evaluate the appropriateness of devising a larger-scale multi-site study of memantine for treatment of dementia in PD.
The proposed assessment schedule was designed to represent use of memantine in general clinical practice and to minimize the burdens to caregivers and patients, who have impaired mobility as well as cognitive function.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00294554
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Laura Marsh, MD||Johns Hopkins University|