Ursodiol in Huntington's Disease

Official Title: “Ursodiol in Huntington's Disease”

The purpose of this study is to evaluate the safety of the drug ursodiol (ursodeoxycholic acid, UDCA) in people with Huntington's disease (HD) and to explore how the compound is processed by the body.

Huntington's disease is an inherited neurodegenerative disease that causes a movement disorder, dementia, and psychiatric and behavioral disturbance in affected individuals.

Tauroursodeoxycholic acid (TUDCA) is a bile acid synthesized in the liver by the conjugation of taurine to ursodeoxycholic acid (UDCA). It is thought to function as an anti-apoptotic agent in HD, evidenced by studies in toxic cell models and both toxic and transgenic rodent models of the disease.

Ursodiol is a commercially-available exogenous form of UDCA, the precursor of TUDCA.

Although the compound has an established dosing, safety, tolerability and efficacy profile in patients with hepatobiliary disorders, gaps exist in the understanding of the pharmacokinetics / pharmacodynamics of the compound, particularly in patients with normal gastrointestinal function, and no human data exist for its therapeutic use in neurodegenerative disorders. The specific aims of this study are:

1. To establish whether treatment with the drug ursodiol will result in measurable levels of its bile acid metabolites in serum and CSF at standard oral doses; and whether a dose-response can be detected using these measures.

2. To establish a preliminary safety and tolerability profile of the drug in subjects with HD.

Intervention(s) in this Clinical Trial

• Drug: ursodiol
  • ursodiol 300 mg twice daily for study days 0 through 28 ursodiol 600mg twice daily on study days 0 through 28
• Drug: placebo
  • placebo 600mg twice daily for study days 0 through 28

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
• Experimental: B
• Placebo Comparator: C

Primary Measures

• Safety measures (complete blood count, chemistry profile, electrocardiogram, urinalysis)
  • Time Frame: 35 days
    Safety Issue?: Yes
• Tolerability measures (adverse event severity)
  • Time Frame: 35 days
    Safety Issue?: Yes
• Pharmacokinetic measures (Serum and CSF levels of bile acids)
  • Time Frame: 28 days
    Safety Issue?: No

Inclusion Criteria:

• All subjects will be age 18 or older
• All subjects will have manifest Huntington disease determined by clinical exam plus either documented prior DNA testing for the HD gene or a documented family history of the disease

Exclusion Criteria:

• Subjects taking oral contraceptives, cholestyramine, colestipol, or aluminum-based antacids will be excluded
• Subjects with known allergy or other contraindication to the study drug will be excluded
• Subjects with bleeding diathesis, or on coumadin or mandatory aspirin will be excluded
• Subjects with unstable medical or psychiatric illness will be excluded
• Subjects with clinically significant lab / EKG abnormalities at screening will be excluded
• Subjects who are currently pregnant or breastfeeding will be excluded

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Oregon Health and Science University Other

Overall Clinical Trial Officials and Contacts

Penelope Hogarth, M.D. Principal Investigator Oregon Health and Science University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00514774

Study ID Number: 00001927

ClinicalTrials.gov Identifier: NCT00514774

Health Authority: United States: Institutional Review Board

Official website for the Huntington Study Group