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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00212316
• Date of registration: 19/09/2005
• Prospective Registration: No
• Primary sponsor: University of Rochester
• Public title: Safety and Tolerability Study of Phenylbutyrate in Huntington's Disease (PHEND-HD)
• Scientific 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
• Date of first enrolment: August 2005
• Target sample size: 60
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00212316
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Steven M. Hersch, MD, PhD
• Affiliation: Co-Chair, Huntington Study Group, Massachusetts General Hospital

• Name: Karl Kieburtz, MD, MPH
• Affiliation: Director, Clinical Trials Coordination Center, University of Rochester

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Huntington's Disease

Intervention(s)

Drug: sodium phenylbutyrate

Primary Outcome(s)

Proportion of subjects able to complete treatment (Week 16)

Secondary Outcome(s)

& total functional capacity.

histone acetylation (levels in WBC; fetal hemoglobin levels in blood),

independence,

Secondary clinical measures at Weeks 4, 10, 16, and 20 include components of the UHDRS:

depletion of glutamine,

Secondary biological indicators of treatment affects at Weeks 4, 10, 16, & 20 include:

adverse events,

markers of neuroprotection (e.g. NAA) via MRS,

changes in vital signs,

Stroop,

and biochemical analyses for pharmacokinetics.

gene expression analyses,

Secondary safety and tolerability outcomes at Weeks 1, 4, 5, 10, 16, & 20 include:

total motor,

and clinical lab assessments.

Secondary ID(s)

R01NS45242

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Kansas

Massachusetts General Hospital

Columbia University

University of Alabama at Birmingham

HP Therapeutics Foundation

Johns Hopkins University

University of Iowa

University of California, San Diego