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

NCT00212316 | Completed Phase 2

• 1 other identifier: R01NS45242
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

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.

Conditions

Huntington's Disease

Keywords

Huntington's Disease; phenylbutyrate; HDAC inhibitors; transcription

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects able to complete treatment (Week 16)

Secondary Outcomes (15)

• 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:

Interventions

sodium phenylbutyrate DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead
• HP Therapeutics Foundation: collaborator
• Massachusetts General Hospital: collaborator
• Columbia University: collaborator
• University of Iowa: collaborator
• University of California, San Diego: collaborator
• University of Kansas: collaborator
• University of Alabama at Birmingham: collaborator
• Johns Hopkins University: collaborator

Study Sites (8)

University of Alabama

Birmingham, Alabama, United States

Location

University of California-San Diego

San Diego, California, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, United States

Location

Johns Hopkins University

Baltimore, Maryland, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

Columbia University

New York, New York, United States

Location

University of Rochester

Rochester, New York, United States

Location

MeSH Terms

Conditions

Huntington Disease

Interventions

4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 19, 2005
• First Posted: September 21, 2005
• Study Start: August 1, 2005
• Study Completion: June 1, 2006
• Last Updated: August 15, 2012

Record last verified: 2007-12

Locations

US (8)