Ursodiol in Huntington's Disease
Information source: Oregon Health and Science University
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Huntington Disease
Intervention: ursodiol (Drug); placebo (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Oregon Health and Science University Official(s) and/or principal investigator(s):
Penelope Hogarth, M.D., Principal Investigator, Affiliation: Oregon Health and Science University
Overall contact:
April Wilson, B.A., Phone: 503-418-1769, Email: wilsonap@ohsu.edu
Summary
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.
Clinical Details
Official title: Ursodiol in Huntington's Disease
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety Study
Primary outcome: Safety measures (complete blood count, chemistry profile, electrocardiogram, urinalysis)Tolerability measures (adverse event severity) Pharmacokinetic measures (Serum and CSF levels of bile acids)
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
April Wilson, B.A., Phone: 503-418-1769, Email: wilsonap@ohsu.edu
Oregon Health & Science University, Portland, Oregon 97239, United States; Recruiting
April Wilson, B.S., Phone: 503-418-1769, Email: wilsonap@ohsu.edu
Pamela Andrews, B.A., Phone: 503-494-0965, Email: andrewsp@ohsu.edu
Penelope Hogarth, M.D., Principal Investigator
Additional Information
Official website for the Huntington Study Group
Related publications: Keene CD, Rodrigues CM, Eich T, Chhabra MS, Steer CJ, Low WC. Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10671-6. Epub 2002 Jul 29. Keene CD, Rodrigues CM, Eich T, Linehan-Stieers C, Abt A, Kren BT, Steer CJ, Low WC. A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington's disease. Exp Neurol. 2001 Oct;171(2):351-60.
Starting date: August 2007
Ending date: October 2008
Last updated: May 28, 2008
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