Safety and Tolerability Study of Phenylbutyrate in Huntington's Disease (PHEND-HD) - Full Text View

Sponsors and Collaborators:	National Institute of Neurological Disorders and Stroke (NINDS) HP Therapeutics Foundation Massachusetts General Hospital University of Rochester Columbia University University of Iowa University of California, San Diego University of Kansas University of Alabama at Birmingham Johns Hopkins University
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00212316

Purpose

The purpose of this study is to evaluate the safety, tolerability and clinical impact of 15-grams daily of sodium phenylbutyrate (phenylbutyrate) in Huntington's disease and to lay the groundwork for possible subsequent trials designed to specifically address its ability to slow or halt the progression of the disease.

Condition	Intervention	Phase
Huntington's Disease	Drug: sodium phenylbutyrate	Phase II

Genetics Home Reference related topics: chorea-acanthocytosis familial encephalopathy with neuroserpin inclusion bodies familial paroxysmal nonkinesigenic dyskinesia Huntington disease McLeod neuroacanthocytosis syndrome

MedlinePlus related topics: Huntington's Disease Hurricanes

Drug Information available for: Sodium phenylbutyrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety Study
Official Title:	Phenylbutyrate Development for Huntington's Disease (PHEND-HD): A Multi-Center, Double-Blind, Placebo-Controlled Study With Open-Label Follow-Up to Determine the Safety and Tolerability of Phenylbutyrate in Subjects With Huntington's Disease

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

Proportion of subjects able to complete treatment (Week 16)

Secondary Outcome Measures:

Secondary safety and tolerability outcomes at Weeks 1, 4, 5, 10, 16, & 20 include:
adverse events,
changes in vital signs,
and clinical lab assessments.
Secondary clinical measures at Weeks 4, 10, 16, and 20 include components of the UHDRS:
total motor,
Stroop,
independence,
& total functional capacity.
Secondary biological indicators of treatment affects at Weeks 4, 10, 16, & 20 include:
markers of neuroprotection (e.g. NAA) via MRS,
histone acetylation (levels in WBC; fetal hemoglobin levels in blood),
depletion of glutamine,
gene expression analyses,
and biochemical analyses for pharmacokinetics.

Estimated Enrollment:	60
Study Start Date:	August 2005
Study Completion Date:	June 2006

Detailed Description:

Huntington's disease (HD) is an autosomal dominant disorder resulting in selective loss of neurons in the striatum—an area of the brain that controls movement, balance, and walking—and other areas of the brain. The disease is characterized by progressive motor and cognitive decline. There is no cure or even plausible treatment to offset the fatal course of the disease. Therefore, any treatment that ameliorates the disease would be of enormous importance.

The purpose of this double-blind, placebo-controlled study—with open-label follow-up—is to determine the safety and tolerability of 15-grams daily of oral phenylbutyrate in people with HD. The study will enroll 60 individuals. Eligible participants will be initially randomized to receive either phenylbutyrate or the matching placebo for 4 weeks.

After the placebo-controlled phase, all participants will enter the open-label phase to receive phenylbutyrate for 12 weeks. Participants will be followed for one month off phenylbutyrate.

This combination of a short-term double-blind, placebo-controlled phase followed by a longer open-label phase will favor the primary goals of detecting toxicity and intolerability while facilitating recruitment and maximizing number of subjects on study drug.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with clinical diagnosis of HD and family history of HD or a CAG repeat expansion greater than or equal to 37
Subjects in stage I or II of illness (TFC greater than or equal to 7)
Subjects must be ambulatory and not requiring skilled nursing care
Age of 18 years or older
Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must confirm to the best of their knowledge that they are not pregnant or plan to get pregnant
Women of childbearing potential must have negative pregnancy test, be non-lactating and use adequate contraception methods, such as oral birth control pills plus a barrier method (i.e. condoms, diaphragm) or IUD during their participation in the study
Subjects currently taking psychotropic medications (including antidepressants and neuroleptics) must be on stable dosages for at least 4 weeks prior to baseline visit and should be maintained on constant dosage throughout the study
Subjects must be capable of providing informed consent and complying with trial procedures
Subjects must be able to take oral medication, a person willing and able to serve as an informant and provide information about the daily dosing of study medication

Exclusion Criteria:

Exposure to phenylbutyrate, valproic acid, probenecid, known HDAC inhibitors or other transcriptionally active compounds within 3 months (90 days) prior to the baseline visit
History of known sensitivity or intolerability to phenylbutyrate, sodium butyrate or sodium acetate
Existence of a known malignancy that might require treatment during the course of this study
Exposure to any investigational drug within 30 days of the baseline visit
Subjects with underlying hematologic, hepatic or renal disease; screening white blood cell (WBC) count less than 3,800/mm3, screening creatinine greater than 2.0 or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
Clinical evidence of unstable medical illness in the investigator's judgment
Clinical illness that requires use of warfarin (Coumadin)
Unstable psychiatric illness defined as psychosis (hallucinations or delusions) untreated major depression or plan for suicide within 90 days of the baseline visit
Current or history of substance (alcohol or drug) abuse within 1 year of the baseline visit
Pregnant women or women who are currently breast-feeding
History of heart failure or other conditions that might be exacerbated by sodium loading

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00212316

Locations

United States, Alabama
University of Alabama
Birmingham, Alabama, United States
United States, California
University of California—San Diego
San Diego, California, United States
United States, Iowa
University of Iowa Hospital and Clinics
Iowa City, Iowa, United States
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States
United States, New York
University of Rochester
Rochester, New York, United States
Columbia University
New York, New York, United States

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

HP Therapeutics Foundation

Massachusetts General Hospital

University of Rochester

Columbia University

University of Iowa

University of California, San Diego

University of Kansas

University of Alabama at Birmingham

Johns Hopkins University

Investigators

Principal Investigator:	Steven M. Hersch, MD, PhD	Co-Chair, Huntington Study Group, Massachusetts General Hospital
Principal Investigator:	Karl Kieburtz, MD, MPH	Director, Clinical Trials Coordination Center, University of Rochester

More Information

Study ID Numbers:	R01NS45242
Study First Received:	September 19, 2005
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00212316
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

Huntington's Disease
phenylbutyrate
HDAC inhibitors
transcription

Study placed in the following topic categories:

Ganglion Cysts
4-phenylbutyric acid
Huntington disease
Basal Ganglia Diseases
Central Nervous System Diseases
Brain Diseases
Neurodegenerative Diseases
Dyskinesias
Cognition Disorders

Chorea
Delirium, Dementia, Amnestic, Cognitive Disorders
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Mental Disorders
Movement Disorders
Dementia
Huntington Disease
Delirium

Additional relevant MeSH terms:

Antineoplastic Agents
Therapeutic Uses
Nervous System Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009