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

NCT ID: NCT00212316

Last Updated: 2012-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2006-06-30

Brief Summary

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.

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.

Conditions

Huntington's Disease

Keywords

Huntington's Disease; phenylbutyrate; HDAC inhibitors; transcription

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

sodium phenylbutyrate

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HP Therapeutics Foundation

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

University of Kansas

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Principal Investigators

Steven M. Hersch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Co-Chair, Huntington Study Group, Massachusetts General Hospital

Karl Kieburtz, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Director, Clinical Trials Coordination Center, University of Rochester

Locations

University of Alabama

Birmingham, Alabama, United States

University of California-San Diego

San Diego, California, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Columbia University

New York, New York, United States

University of Rochester

Rochester, New York, United States

Countries

United States

Other Identifiers

R01NS45242

Identifier Type: -

Identifier Source: org_study_id