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

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ClinicalTrials.gov Identifier: NCT02603926
Recruitment Status : Completed
First Posted : November 13, 2015
Results First Posted : December 6, 2018
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Randi J. Hagerman, MD, University of California, Davis

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fragile X-associated Tremor/Ataxia Syndrome
Intervention Drug: Allopregnanolone
Enrollment 6
Recruitment Details Participants were recruited by invitation from the University of California, Davis (UC Davis), MIND Institute's Fragile X Research and Treatment Center.
Pre-assignment Details  
Arm/Group Title Allopregnanolone
Hide Arm/Group Description Subjects will receive and 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.
Period Title: Overall Study
Started 6
Completed 6
Not Completed 0
Arm/Group Title Allopregnanolone
Hide Arm/Group Description

Subjects will receive and 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.

Allopregnanolone

Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants
68.3
(57 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
0
   0.0%
Male
6
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Hispanic or Latino
1
  16.7%
Not Hispanic or Latino
5
  83.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
5
  83.3%
More than one race
1
  16.7%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants
6
1.Primary Outcome
Title California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score
Hide Description 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.
Time Frame Baseline/pre-treatment and 14 weeks/post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Primary outcome measure (CVLT2) was completed for all enrolled subjects.
Arm/Group Title Allopregnanolone
Hide Arm/Group Description:
Subjects will receive and 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.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline/Pre-Treatment 34.0  (7.5)
14 Weeks/Post-Treatment 33.5  (6.3)
2.Secondary Outcome
Title Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score
Hide Description 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.
Time Frame Baseline/pre-treatment and 14 weeks/post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
BDS-2 was completed for all enrolled subjects.
Arm/Group Title Allopregnanolone
Hide Arm/Group Description:
Subjects will receive and 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.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline/Pre-Treatment 12.7  (3.1)
14 Weeks/Post-Treatment 15.3  (3.8)
3.Secondary Outcome
Title CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
Hide Description 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.
Time Frame Baseline/pre-treatment and 14 weeks/post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
CATSYS DTD TI was completed by all subjects.
Arm/Group Title Allopregnanolone
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: meters per second (m/s)
Baseline/Pre-Treatment, Right-Hand 0.87  (0.49)
Baseline/Pre-Treatment, Left-Hand 0.74  (0.29)
14 Weeks/Post-Treatment, Right-Hand 0.79  (0.59)
14 Weeks/Post-Treatment, Left-Hand 0.65  (0.26)
4.Secondary Outcome
Title Hippocampal Volume, as Measured by Structural MRI
Hide Description 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.
Time Frame Baseline/pre-treatment and 14 weeks/post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
1 subject was unable to undergo structural MRI procedure at baseline and post-treatment.
Arm/Group Title Allopregnanolone
Hide Arm/Group Description:
Subjects will receive and 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.
Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: cubic centimeters
Baseline/Pre-Treatment 5.87  (1.00)
14 Weeks/Post-Treatment 5.84  (1.18)
Time Frame 14 weeks (from baseline to post-treatment).
Adverse Event Reporting Description The Richmond Agitation Sedation Scale (RASS) was administered before, during, and after each infusion; it was not a prespecified outcome measure, rather a safety precaution. Infusions were to be terminated if the score on RASS fellow below -1 (drowsy) during the infusion. Each participant was also required to be accompanied by a chaperone, who drove the participant home from the infusion center and remained with the participant for at least 20 hours thereafter to monitor for adverse effects.
 
Arm/Group Title Allopregnanolone
Hide Arm/Group Description Subjects will receive and 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.
All-Cause Mortality
Allopregnanolone
Affected / at Risk (%)
Total   0/6 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Allopregnanolone
Affected / at Risk (%)
Total   0/6 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Allopregnanolone
Affected / at Risk (%)
Total   0/6 (0.00%) 
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Randi Hagerman
Organization: UC Davis MIND Institute
Phone: 916-703-0247
EMail: rjhagerman@ucdavis.edu
Layout table for additonal information
Responsible Party: Randi J. Hagerman, MD, University of California, Davis
ClinicalTrials.gov Identifier: NCT02603926     History of Changes
Other Study ID Numbers: 720668
First Submitted: November 5, 2015
First Posted: November 13, 2015
Results First Submitted: October 17, 2018
Results First Posted: December 6, 2018
Last Update Posted: December 6, 2018