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

NCT02603926 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 720668
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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).

Conditions

Fragile X-associated Tremor/Ataxia Syndrome

Outcome Measures

Primary Outcomes (1)

• California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score

  California Verbal Learning Test II (CVLT2) is an assessment measuring working memory. Trials 1-5 measure the total number of words remembered after 5 repeated trials and are summed to generate a raw score (called Trial 1-5 Free Recall Total Raw Score) ranging from 0 to 80, with higher scores reflecting better working memory. Mean and standard deviation for raw score at baseline/pre-treatment and at 14 weeks/post-treatment are presented here.

  Baseline/pre-treatment and 14 weeks/post-treatment

Secondary Outcomes (3)

• Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score

  Baseline/pre-treatment and 14 weeks/post-treatment

• CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)

  Baseline/pre-treatment and 14 weeks/post-treatment

• Hippocampal Volume, as Measured by Structural MRI

  Baseline/pre-treatment and 14 weeks/post-treatment

Study Arms (1)

Allopregnanolone

EXPERIMENTAL

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.

Drug: Allopregnanolone

Interventions

Allopregnanolone 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.

Also known as: 5α-pregnan-3α-ol-20-one, 3α,5α-tetrahydroprogesterone, brexanolone

Allopregnanolone

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Randi J. Hagerman, MD: lead

Study Sites (1)

UC Davis MIND Institute

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Fragile X Tremor Ataxia Syndrome

Interventions

Pregnanolone; brexanolone

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

This preliminary trial was conducted to obtain evidence of treatment benefits in a small sample, and thus the study was not powered to detect statistical significance while controlling for multiple comparisons. There was also no placebo group.

Results Point of Contact

• Title: Dr. Randi Hagerman
• Organization: UC Davis MIND Institute

rjhagerman@ucdavis.edu

916-703-0247

Study Officials

• Randi J Hagerman, MD

  UC Davis MIND Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director, MIND Institute

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 13, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2017
• Last Updated: December 6, 2018
• Results First Posted: December 6, 2018

Record last verified: 2018-11

Locations

US (1)