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

University of Rochester

Status and phase

Completed

Phase 2

Conditions

Huntington's Disease

Treatments

Drug: sodium phenylbutyrate

Study type

Interventional

Funder types

Other

Identifiers

NCT00212316

R01NS45242

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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