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

Fragile X-associated Tremor/Ataxia Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02603926
• Other study ID #: 720668
• Status: Completed
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: December 2017

Study information

• Verified date: November 2018
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Fragile X Syndrome
• Fragile X-associated Tremor/Ataxia Syndrome
• Syndrome
• Tremor

Intervention

Drug:
• Allopregnanolone
Allopregnanolone is an endogenous inhibitory pregnane neurosteroid. It is synthesized from progesterone, and is a potent positive allosteric modulator of the action of ?-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-ß-cyclodextrin with 0.9% sodium chloride injection solution.

Locations

Country	Name	City	State
United States	UC Davis MIND Institute	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Randi J. Hagerman, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score	The BDS-2 is a validated 9-item assessment measuring the ability to regulate purposeful, goal-directed activity and to engage in activities of daily living, with focus on motor items. Each of the 9 items is scored on a scale of 0 to 3, resulting in a summed total score ranging from 0 to 27. Higher scores reflect fewer errors and stronger ability to regulate motor activities. Mean and standard deviation for total score at baseline/pre-treatment and at 14 weeks/post-treatment are presented here.	Baseline/pre-treatment and 14 weeks/post-treatment
Secondary	CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)	The CATSYS system is a portable device recording various measures of neuromotor control, including tremor. The CATSYS Dot-to-Dot Tremor Intensity (DTD TI) protocol quantifies tremor by having a participant hold a tremor pen as they would an ordinary pen, with the elbow joint bent at a right angle and free of body contact, and the pen positioned approximately 4 inches from the navel. Subjects are instructed to use the pen first to tap the center of two circular stickers, approximately 0.5 inch in diameter, placed on opposite ends of the bottom portion of the computer monitor; then, subjects are instructed to trace a line across the table using the tremor pen. The pen is connected to a computer with sensors that measure tremor intensity (TI) in units of meters per second (m/s). Larger values reflect greater tremor intensity. Mean right-hand and left-hand TI and standard deviation at baseline/pre-treatment and at 14 weeks/post-treatment are reported here.	Baseline/pre-treatment and 14 weeks/post-treatment
Secondary	Hippocampal Volume, as Measured by Structural MRI	Patients will undergo structural Magnetic Resonance Imaging (MRI) at baseline/pre-treatment and at 14 weeks/post-treatment. The MRI is interpreted by a trained clinician and hippocampal volume in cubic centimeters is measured and recorded. Larger values reflect greater volumes of the hippocampus, and greater hippocampal volume post-treatment may be indicative of increased neurogenesis. Mean hippocampal volume and standard deviation at baseline/pre-treatment and post-treatment is reported here.	Baseline/pre-treatment and 14 weeks/post-treatment