Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone

NCT ID: NCT02603926

Last Updated: 2018-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2017-12-31

Brief Summary

The purpose of this study is to examine the safety and efficacy of Allopregnanolone as a possible treatment for symptoms of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).

Detailed Description

This study includes a screening visit with several assessments, followed by an open-label medication trial of Allopregnanolone for 12 weeks and an end-point evaluation to assess for changes. Assessments include blood draws for genetic and safety laboratory testing, neurological and physical exam and medical history, cognitive testing, and motor testing.

Study record was updated in October 2018 to include adverse events and outcome measure reporting. Study record was updated in November 2018 in response to requests to (1) specify time frame of reported outcome measures, (2) clarify that the RASS was a safety monitoring tool, not a prespecified outcome measure, and as such will not be reported as an outcome measure, and (3) upload a version of the study protocol and statistical analysis plan with the required title page and statistical analysis plan information.

Conditions

Fragile X-associated Tremor/Ataxia Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Allopregnanolone

Subjects will receive an intravenous infusion of Allopregnanolone at escalating doses of 2mg, 4mg, and 6mg once weekly over a three week period. The highest dose tolerated without sedation will be held stable for the remaining weekly infusions, for a total of 12 infusions.

Group Type: EXPERIMENTAL

Allopregnanolone

Intervention Type: DRUG

Allopregnanolone is an endogenous inhibitory pregnane neurosteroid. It is synthesized from progesterone, and is a potent positive allosteric modulator of the action of γ-aminobutyric acid at GABAA receptor. Subjects will receive up to 12 infusions in the study. Subjects will all begin with 2.0 mg dosage. If tolerated, the next infusion will be 4.0 mg, and if that is tolerated, the next infusion will be 6.0 mg. Subject infusions will remain stable at the highest dosage tolerated for the remainder of the study. Each infusion will consist of 2.0 mg, 4.0 mg, or 6.0 mg aliquots of the 0.5 mg/ml allopregnanolone in 6% sulfobutylether-β-cyclodextrin with 0.9% sodium chloride injection solution.

Interventions

Allopregnanolone

Allopregnanolone is an endogenous inhibitory pregnane neurosteroid. It is synthesized from progesterone, and is a potent positive allosteric modulator of the action of γ-aminobutyric acid at GABAA receptor. Subjects will receive up to 12 infusions in the study. Subjects will all begin with 2.0 mg dosage. If tolerated, the next infusion will be 4.0 mg, and if that is tolerated, the next infusion will be 6.0 mg. Subject infusions will remain stable at the highest dosage tolerated for the remainder of the study. Each infusion will consist of 2.0 mg, 4.0 mg, or 6.0 mg aliquots of the 0.5 mg/ml allopregnanolone in 6% sulfobutylether-β-cyclodextrin with 0.9% sodium chloride injection solution.

Intervention Type: DRUG

Other Intervention Names

5α-pregnan-3α-ol-20-one; 3α,5α-tetrahydroprogesterone; brexanolone

Eligibility Criteria

Inclusion Criteria

• Fragile X premutation carrier status (55 to 200 CGG repeats in FMR1),
• Diagnosis of FXTAS including an intention tremor and/or ataxia and/or deficits on the BDS-2 demonstrating executive function deficits.

Exclusion Criteria

• other genetic problems in addition to the premutation
• a history of significant brain trauma
• significant substance abuse
• inability to follow the protocol
• liver or kidney disease
• heart failure
• active cancer
• other serious systemic disease
• current use of phenytoin

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Randi J. Hagerman, MD

OTHER

Sponsor Role: lead

Responsible Party

Randi J. Hagerman, MD

Medical Director, MIND Institute

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Randi J Hagerman, MD

Role: PRINCIPAL_INVESTIGATOR

UC Davis MIND Institute

Locations

UC Davis MIND Institute

Sacramento, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

720668

Identifier Type: -

Identifier Source: org_study_id