Trial Outcomes & Findings for Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone (NCT NCT02603926)
NCT ID: NCT02603926
Last Updated: 2018-12-06
Results Overview
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.
COMPLETED
PHASE2
6 participants
Baseline/pre-treatment and 14 weeks/post-treatment
2018-12-06
Participant Flow
Participants were recruited by invitation from the University of California, Davis (UC Davis), MIND Institute's Fragile X Research and Treatment Center.
Participant milestones
| Measure |
Allopregnanolone
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.
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|---|---|
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Overall Study
STARTED
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6
|
|
Overall Study
COMPLETED
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6
|
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Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone
Baseline characteristics by cohort
| Measure |
Allopregnanolone
n=6 Participants
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
|
|---|---|
|
Age, Continuous
|
68.3 years
n=5 Participants
|
|
Sex: Female, Male
Female
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0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline/pre-treatment and 14 weeks/post-treatmentPopulation: Primary outcome measure (CVLT2) was completed for all enrolled subjects.
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.
Outcome measures
| Measure |
Allopregnanolone
n=6 Participants
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.
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|---|---|
|
California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score
Baseline/Pre-Treatment
|
34.0 score on a scale
Standard Deviation 7.5
|
|
California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score
14 Weeks/Post-Treatment
|
33.5 score on a scale
Standard Deviation 6.3
|
SECONDARY outcome
Timeframe: Baseline/pre-treatment and 14 weeks/post-treatmentPopulation: BDS-2 was completed for all enrolled subjects.
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.
Outcome measures
| Measure |
Allopregnanolone
n=6 Participants
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.
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|---|---|
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Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score
Baseline/Pre-Treatment
|
12.7 score on a scale
Standard Deviation 3.1
|
|
Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score
14 Weeks/Post-Treatment
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15.3 score on a scale
Standard Deviation 3.8
|
SECONDARY outcome
Timeframe: Baseline/pre-treatment and 14 weeks/post-treatmentPopulation: CATSYS DTD TI was completed by all subjects.
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.
Outcome measures
| Measure |
Allopregnanolone
n=6 Participants
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.
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|---|---|
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CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
Baseline/Pre-Treatment, Right-Hand
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0.87 meters per second (m/s)
Standard Deviation 0.49
|
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CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
Baseline/Pre-Treatment, Left-Hand
|
0.74 meters per second (m/s)
Standard Deviation 0.29
|
|
CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
14 Weeks/Post-Treatment, Right-Hand
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0.79 meters per second (m/s)
Standard Deviation 0.59
|
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CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
14 Weeks/Post-Treatment, Left-Hand
|
0.65 meters per second (m/s)
Standard Deviation 0.26
|
SECONDARY outcome
Timeframe: Baseline/pre-treatment and 14 weeks/post-treatmentPopulation: 1 subject was unable to undergo structural MRI procedure at baseline and post-treatment.
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.
Outcome measures
| Measure |
Allopregnanolone
n=5 Participants
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.
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|---|---|
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Hippocampal Volume, as Measured by Structural MRI
14 Weeks/Post-Treatment
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5.84 cubic centimeters
Standard Deviation 1.18
|
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Hippocampal Volume, as Measured by Structural MRI
Baseline/Pre-Treatment
|
5.87 cubic centimeters
Standard Deviation 1.00
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Adverse Events
Allopregnanolone
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place