Ursodiol in Huntington's Disease

NCT ID: NCT00514774

Last Updated: 2009-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Study Completion Date

2009-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Huntington Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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A

Group Type EXPERIMENTAL

ursodiol

Intervention Type DRUG

ursodiol 300 mg twice daily for study days 0 through 28

ursodiol 600mg twice daily on study days 0 through 28

B

Group Type EXPERIMENTAL

ursodiol

Intervention Type DRUG

ursodiol 300 mg twice daily for study days 0 through 28

ursodiol 600mg twice daily on study days 0 through 28

C

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo 600mg twice daily for study days 0 through 28

Interventions

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ursodiol

ursodiol 300 mg twice daily for study days 0 through 28

ursodiol 600mg twice daily on study days 0 through 28

Intervention Type DRUG

placebo

placebo 600mg twice daily for study days 0 through 28

Intervention Type DRUG

Other Intervention Names

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Ursodeoxycholic acid UDCA

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Huntington Study Group

NETWORK

Sponsor Role collaborator

Huntington Society of Canada

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role lead

Responsible Party

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Oregon Health & Science University

Principal Investigators

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Penelope Hogarth, M.D.

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

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Oregon Health & Science University

Portland, Oregon, United States

Site Status

Countries

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United States

References

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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. doi: 10.1073/pnas.162362299. Epub 2002 Jul 29.

Reference Type BACKGROUND
PMID: 12149470 (View on PubMed)

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. doi: 10.1006/exnr.2001.7755.

Reference Type BACKGROUND
PMID: 11573988 (View on PubMed)

Other Identifiers

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00001927

Identifier Type: -

Identifier Source: org_study_id

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