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

Huntington's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00212316
• Other study ID #: R01NS45242
• Status: Completed
• Phase: Phase 2
• First received: September 19, 2005
• Last updated: August 14, 2012
• Start date: August 2005
• Est. completion date: June 2006

Study information

• Verified date: December 2007
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• sodium phenylbutyrate

Locations

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

Sponsors (9)

Lead Sponsor	Collaborator
University of Rochester	Columbia University, HP Therapeutics Foundation, Johns Hopkins University, Massachusetts General Hospital, University of Alabama at Birmingham, University of California, San Diego, University of Iowa, University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

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