Safety and Tolerability Study of Phenylbutyrate in Huntington's Disease (PHEND-HD)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|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|
- Proportion of subjects able to complete treatment (Week 16)
- 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,
- & 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.
|Study Start Date:||August 2005|
|Study Completion Date:||June 2006|
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.
|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|
|New York, New York, United States|
|University of Rochester|
|Rochester, New York, United States|
|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|