Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00212316
Recruitment Status : Completed
First Posted : September 21, 2005
Last Update Posted : August 15, 2012
HP Therapeutics Foundation
Massachusetts General Hospital
Columbia University
University of Iowa
University of California, San Diego
University of Kansas
University of Alabama at Birmingham
Johns Hopkins University
Information provided by:
University of Rochester

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.

Condition or disease Intervention/treatment Phase
Huntington's Disease Drug: sodium phenylbutyrate Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
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
Study Start Date : August 2005
Actual Study Completion Date : June 2006

Primary Outcome Measures :
  1. Proportion of subjects able to complete treatment (Week 16)

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00212316

Layout table for location information
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
Columbia University
New York, New York, United States
University of Rochester
Rochester, New York, United States
Sponsors and Collaborators
University of Rochester
HP Therapeutics Foundation
Massachusetts General Hospital
Columbia University
University of Iowa
University of California, San Diego
University of Kansas
University of Alabama at Birmingham
Johns Hopkins University
Layout table for investigator information
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
Layout table for additonal information Identifier: NCT00212316    
Other Study ID Numbers: R01NS45242
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: August 15, 2012
Last Verified: December 2007
Keywords provided by University of Rochester:
Huntington's Disease
HDAC inhibitors
Additional relevant MeSH terms:
Layout table for MeSH terms
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
4-phenylbutyric acid
Antineoplastic Agents