Ursodiol in Huntington's Disease

Huntington Disease Clinical Trial

— UDCA-HD  

Official title:

Ursodiol in Huntington's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00514774
• Other study ID #: 00001927
• Status: Active, not recruiting
• Phase: Phase 1
• First received: August 8, 2007
• Last updated: February 4, 2009
• Start date: August 2007
• Est. completion date: June 2009

Study information

• Verified date: February 2009
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Huntington Disease

Intervention

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

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
Oregon Health and Science University	Huntington Society of Canada, Huntington Study Group

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety measures (complete blood count, chemistry profile, electrocardiogram, urinalysis)		35 days	Yes
Primary	Tolerability measures (adverse event severity)		35 days	Yes
Primary	Pharmacokinetic measures (Serum and CSF levels of bile acids)		28 days	No

External Links

•   Official website for the Huntington Study Group