A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease - Full Text View

Purpose

Huntington disease is characterized by difficulties in movement and thinking. Psychological disturbances including irritability, aggression, loss of interest, depressed mood, obsessions and compulsions, also represent common symptoms of HD. These symptoms are distressing both for HD patients and their caregivers, contribute to the loss of ability to carry out activities of daily living, and present a major treatment challenge for physicians. The goal of this study is to determine the effect of memantine on movement, thinking and emotional difficulties in HD patients. Memantine is a medication originally approved for the treatment of aggression and agitation in patients with moderate-to-severe Alzheimer's disease (AD), which has also recently been shown to improve the behavioural and neuropathological symptoms in a mouse model of Huntington Disease (HD).

Condition	Intervention	Phase
Huntington Disease	Drug: Memantine Other: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease; a Phase IIb Study

Resource links provided by NLM:

Genetics Home Reference related topics: Huntington disease chorea-acanthocytosis

MedlinePlus related topics: Huntington's Disease

Drug Information available for: Memantine Memantine hydrochloride

Genetic and Rare Diseases Information Center resources: Huntington Disease

U.S. FDA Resources

Further study details as provided by University of British Columbia:

Primary Outcome Measures:

Utility of TRACK-HD study endpoints in a clinical trial setting [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To examine the clinical utility of novel trial endpoints (such as Putaminal NAA measured by MRS) developed in the TRACK-HD study in the setting of a placebo-controlled therapeutic trial.

Secondary Outcome Measures:

Neuropsychiatric and Cognitive Test Scores [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To examine effect of memantine versus placebo on the scores of: a) the irritability and agitation/aggression sub-categories of the Neuropsychiatric Inventory (NPI), and also the total NPI, b) cognitive tests: Circle Tracing , Symbol Digit Modality, Stroop Word Reading, and Spot the Change, c) total HD-ADL, d) total UHDRS, and the UHDRS sub-scale: Cognitive, Behavioural, Functional, and Independence scales. e) In patients recruited at the UBC study site, the effect on striatal N-acetyl aspartate levels (a measure of neuronal dysfunction) will be assessed by Magnetic Resonance Spectroscopy.


Enrollment:	19
Study Start Date:	September 2011
Study Completion Date:	November 2012
Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Memantine NMDA Receptor Antagonist	Drug: Memantine oral tablet, 1 BID, 24 weeks Other Names: Ebixa DIN 02260638 Namenda
Placebo Comparator: Sugar pill	Other: Placebo oral tablet, 1 BID, 24 weeks

Detailed Description:

TRACK-HD was a multi-centre, multi-national, prospective, observational study of pre-manifest and early Huntington's disease (HD) with a control group of volunteers not carrying the HD mutation. The goal of the project was to contribute essential methodology that will form the basis for clinical trials in pre-manifest and early HD. TRACK-HD complemented existing observational studies (e.g., Predict-HD, PHAROS, COHORT), sharing some features, but also having areas of unique emphasis.

The UBC site recruited 90 subjects including 30 control subjects, 30 asymptomatic pre-manifest HD gene carriers and 30 subjects with early symptoms of HD (stage 1 or 2). All subjects were assessed using the TRACK-HD battery at baseline, 1 year, 2 years, and 3 years. Following the fourth visit (3 year assessment), the TRACK-HD study will be completed, and the 30 subjects with early symptoms of HD will be invited to enroll in the MITIGATE-HD Study.

The MITIGATE-HD study is a single center Phase IIb,out-patient,randomized, double-blind, placebo-controlled trial of memantine treatment in subjects with Huntington disease (HD). The study will evaluate Memantine 10 mg two times daily (BID) administered orally (PO) for six months (24 weeks) compared with matching placebo BID. Safety and tolerability will be assessed by recording of adverse events and by monitoring of vital signs, physical examinations, and suicidality risk scores.

The TRACK-HD assessment battery will be administered to all subjects after six months of study drug administration. The effects of memantine will be evaluated both against placebo as well as compared to the previous 3 years of observational data from the TRACK-HD Study.

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

To be eligible for the study, a subject must be enrolled in the early HD cohort of the TRACK-HD study and:

be at least 18 years of age and not older than 65
able to provide written consent
carry the abnormal HD gene and show early symptoms of HD
be able and willing to comply with study requirements, including travel to study center
have no metal implants to be suitable for MRI scans and able to tolerate them
able to tolerate blood draws
be of stable medical, psychiatric and neurological health at the time of enrollment
not have a history of significant head injury
not have a history of significant hand injury that would prevent either writing or performing rapid computer tasks
not be abusing drugs and/or alcohol that may cause failure to comply with study procedures
not be currently participating in PREDICT-HD or a clinical drug trial.

Exclusion Criteria:

Prospective subjects will be excluded if:

they are younger than 18 years of age and older than 65
they are unable to provide written consent
they show advanced symptoms of HD if they are HD gene carriers
they are unwilling to comply with study requirements, including travel to study center
they are unsuitable for MRI (e.g, claustrophobia, metal implants) or unable to tolerate them
they are unable to tolerate blood draws; or,
they have a major psychiatric disorder, concomitant significant neurological disorder or concomitant significant medical illness at the time of enrollment
they have a history of CNS disease or significant head injury; or,
they have a history of significant hand injury that would prevent either writing or performing rapid computer tasks; or,
they are likely to be non-compliant with study procedures due to drug and/or alcohol abuse; or,
they are participating in PREDICT-HD or a clinical drug trial at the time of enrollment.
they are not sighted
English is not their first language
they are currently or treated within the last 6 months with antipsychotic medications, including the traditional neuroleptics such as haloperidol as well as the atypical antipsychotics risperidone, clozapine, quetiapine and olanzapine
they are use phenothiazine-derivative antiemetic medications such as prochlorperazine, metoclopramide, promethazine and Inapsine on a regular basis (greater than 3 times per month)
they have a history of learning disability and/or mental retardation.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01458470

Locations


Canada, British Columbia
The Centre for Huntington Disease
Vancouver, British Columbia, Canada, V6T 2B5

Sponsors and Collaborators

University of British Columbia

Huntington Society of Canada

Huntington Study Group

Investigators


Principal Investigator:	Blair R. Leavitt, MD,CM,FRCPC	University of British Columbia
Study Chair:	Michael R. Hayden, MD,ChB,PhD	The University of British Columbia

More Information

Additional Information:

The Huntington Study Group This link exits the ClinicalTrials.gov site

The Huntington Society of Canada This link exits the ClinicalTrials.gov site

Health Canada This link exits the ClinicalTrials.gov site


Responsible Party:	University of British Columbia
ClinicalTrials.gov Identifier:	NCT01458470 History of Changes
Other Study ID Numbers:	H11-01364
Study First Received:	October 20, 2011
Last Updated:	March 17, 2014
Health Authority:	Canada: Health Canada

Keywords provided by University of British Columbia:


huntington huntingtin memantine ebixa namenda

Additional relevant MeSH terms:


Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Dementia Chorea Dyskinesias Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn	Cognition Disorders Neurocognitive Disorders Mental Disorders Memantine Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on September 30, 2016

A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease (MITIGATE-HD)