Study of Memantine to Treat Huntington's Disease

• Sponsor: Jody Corey-Bloom, MD, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00652457
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 50
• Locations: 3
• Arms: 2
• Actual Duration (Months): 59.1
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To determine if memantine in doses of 10 mg BID affects memory, cognition, and behavior in patients with Huntington's disease (HD).

Condition or Disease	Intervention/Treatment	Phase
Huntington's Disease	Drug: Memantine	Phase 4

Detailed Description

Results of several published clinical trials suggest that memantine has a beneficial effect in dementing conditions, such as Alzheimer's disease; however, the effects of memantine on cognitive and behavioral function in HD are unknown. Our hypotheses are that HD patients who are administered memantine will show improved performance on psychometric tests of memory and executive functions in addition to behavior and that patients treated with memantine will show more improvement after six months than after three months of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Memantine for Cognitive and Behavioral Dysfunction in Huntington's Disease"
• Actual Study Start Date: Nov 23, 2004
• Actual Primary Completion Date: Oct 28, 2009
• Actual Study Completion Date: Oct 28, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Memantine Memantine 10 mg BID for three months	Drug: Memantine; 10 mg BID x 3 months; Other Names: Namenda
Placebo Comparator: Placebo Placebo 10 mg BID for three months	Drug: Memantine; 10 mg BID x 3 months; Other Names: Namenda

Outcome Measures

Primary Outcome Measures

1. Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) [Baseline, 3 months from start of drug treatment, 6 months from start of drug treatment]

   The HVLT-R consists of 3 parts. Free recall has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from the respective later time point value. Imputation methods were used to determine values for all alive patients missing the post-baseline assessments. This tool is being used to measure cognitive function, specifically memory.

Secondary Outcome Measures

1. Neuropsychiatric Inventory (NPI) [Baseline, 3 months from start of drug treatment, 6 months from start of drug treatment]

   The Neuropsychiatric Inventory (NPI) assesses the frequency and severity of 12 common behavioral symptoms in dementia. The NPI Score is calculated by multiplying the total reported frequency by the severity score, with a theoretical range of 0-1704: high scores indicating greater frequency by severity. The change between 2 or more time points is being reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women aged 18 or older.

• Diagnosis of HD with current complaints of memory or concentration difficulties.

• Dementia Rating Scale score of <129, to ensure that patients have sufficient cognitive impairment.

• Adequate visual and auditory acuity to allow neuropsychological testing.

• Good general health with no additional diseases expected to interfere with the study.

• Patient is not institutionalized.

• Sufficient English skills to complete all testing without assistance of an English language interpreter.

• Availability of a responsible caregiver who agrees to supervise administration of study drug, monitor the patient's compliance and adverse events, and accompany the patient to all clinic visits.

Exclusion Criteria:

• 1. Any significant neurologic disease other than HD.

• Severe psychotic features or other severe psychiatric problems within the last three months which could lead to difficulty complying with the protocol.

• History of alcohol or substance abuse within the past two years (DSM IV criteria).

• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.

• History of MI in the past year or head trauma with loss of consciousness greater than 20 minutes.

• Insulin-requiring diabetes.

• Use of any FDA approved cognitive enhancing prescription medications or investigational drugs within 30 days.

• Use of ginkgo biloba or DHEA within four weeks prior to baseline.

• Use of narcotic analgesics within 4 weeks prior to baseline.

• Patients who, in the investigator's opinion, would not comply with study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego	La Jolla	California	United States	92037
2	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
3	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Jody Corey-Bloom, MD, PhD
• Forest Laboratories

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jody Corey-Bloom, MD, PhD, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00652457
• Other Study ID Numbers: MEM-HD
• First Posted: Apr 3, 2008
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Additional relevant MeSH terms: Huntington Disease; Memantine

Study Results

Participant Flow

Recruitment Details	Sixty-five participants were screened for eligibility; 6 individuals failed screening by not meeting inclusion criteria forthe study; 9 declined to participate. Fifty participants were then randomized.

Arm/Group Title	Memantine, Then Memantine	Placebo, Then Memantine
Arm/Group Description	Participants first received 10 mg Memantine twice a day for 3 months. No washout. Participants continued on 10 mg Memantine twice a day for another 3 months.	Participants first received Placebo twice a day for 3 months. No washout. Participants then received 10 mg Memantine twice a day for 3 months.
Period Title: Overall Study
STARTED	23	27
COMPLETED	23	27
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Total of all reporting groups due to age of study. Data was not analyzed per arm.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (NA)
Sex: Female, Male (Count of Participants)
Female	31 62%
Male	19 38%

Outcome Measures

1. Primary Outcome

Title	Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall)
Description	The HVLT-R consists of 3 parts. Free recall has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from the respective later time point value. Imputation methods were used to determine values for all alive patients missing the post-baseline assessments. This tool is being used to measure cognitive function, specifically memory.
Time Frame	Baseline, 3 months from start of drug treatment, 6 months from start of drug treatment

Outcome Measure Data

Analysis Population Description

Due to the age of this study (2003), the data is no longer accessible. We have been moved a number of times in 17 years and that data has been lost.

Arm/Group Title	Memantine, Then Memantine	Placebo, Then Memantine
Arm/Group Description	Participants first received 10 mg Memantine twice a day for 3 months. No washout. Participants continued on 10 mg Memantine twice a day for another 3 months.	Participants first received Placebo twice a day for 3 months. No washout. Participants then received 10 mg Memantine twice a day for 3 months.
Measure Participants	0	0

2. Secondary Outcome

Title	Neuropsychiatric Inventory (NPI)
Description	The Neuropsychiatric Inventory (NPI) assesses the frequency and severity of 12 common behavioral symptoms in dementia. The NPI Score is calculated by multiplying the total reported frequency by the severity score, with a theoretical range of 0-1704: high scores indicating greater frequency by severity. The change between 2 or more time points is being reported.
Time Frame	Baseline, 3 months from start of drug treatment, 6 months from start of drug treatment

Outcome Measure Data

Analysis Population Description

Due to the age of this study (2003), the data is no longer accessible. We have been moved a number of times in 17 years and that data has been lost.

Arm/Group Title	Memantine, Then Memantine	Placebo, Then Memantine
Arm/Group Description	Participants first received 10 mg Memantine twice a day for 3 months. No washout. Participants continued on 10 mg Memantine twice a day for another 3 months.	Participants first received Placebo twice a day for 3 months. No washout. Participants then received 10 mg Memantine twice a day for 3 months.
Measure Participants	0	0

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Due to the age of this study (2003), the data regarding individual arms is no longer accessible. We have been moved a number of times in 17 years and that data has been lost.
Arm/Group Title	Memantine, Then Memantine		Placebo, Then Memantine
Arm/Group Description	Participants first received 10 mg Memantine twice a day for 3 months. No washout. Participants continued on 10 mg Memantine twice a day for another 3 months.		Participants first received Placebo twice a day for 3 months. No washout. Participants then received 10 mg Memantine twice a day for 3 months.
All Cause Mortality
	Memantine, Then Memantine		Placebo, Then Memantine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/27 (0%)
Serious Adverse Events
	Memantine, Then Memantine		Placebo, Then Memantine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Memantine, Then Memantine		Placebo, Then Memantine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		1/27 (3.7%)
Gastrointestinal disorders
Diarrhea	2/23 (8.7%)	2	0/27 (0%)	0
Nervous system disorders
Dizziness	2/23 (8.7%)	2	1/27 (3.7%)	1

Limitations/Caveats

Due to the age of this study (2003), the data is no longer accessible. We have been moved a number of times in 17 years and that data has been lost. The only information we have was provided here in the Results section.

More Information

Certain Agreements

All Principal Investigators ARE 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.