Fragile X-associated Tremor/Ataxia SyndromePhase 2NCT02603926
Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone
A Phase 2 study testing Allopregnanolone in people with Fragile X-associated Tremor/Ataxia Syndrome, run by Randi J. Hagerman, MD at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Fragile X-associated Tremor/Ataxia Syndrome
- What is being tested?
- Allopregnanolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- active cancer
- other serious systemic disease
- current use of phenytoin
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis MIND Institute
Sacramento, California, 95817
About this study
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).
Read the 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.
- Being tested
- Allopregnanolone
- Medical subject headings
- Fragile X Tremor Ataxia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopregnanoloneDrug
Also called 5α-pregnan-3α-ol-20-one, 3α,5α-tetrahydroprogesterone, brexanolone
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Allopregnanolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline/pre-treatment and 14 weeks/post-treatment
Secondary outcomes (3)
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.
Measured: Baseline/pre-treatment and 14 weeks/post-treatment
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.
Measured: Baseline/pre-treatment and 14 weeks/post-treatment
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.
Measured: Baseline/pre-treatment and 14 weeks/post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2015 (estimated)
- Study startOct 2015
- Primary completionDec 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fragile X-associated Tremor/Ataxia SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Randi J. Hagerman, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Randi J. Hagerman, MD, University of California, Davis
- Investigators
- Randi J Hagerman, MD, Principal investigator, UC Davis MIND Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02603926
- Sponsor's protocol ID
- 720668
- Status last verified
- Nov 2018
- First submitted
- 5 Nov 2015
- Last updated
- 6 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone
- ClinicalTrials.gov ID
- NCT02603926
- Acronym / sponsor ID
- 720668
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Randi J. Hagerman, MDUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 13 Nov 2015 (estimated)
- Results
- Posted 6 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allopregnanolone | Experimental | Drug: AllopregnanoloneSubjects 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. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopregnanoloneAlso: 5α-pregnan-3α-ol-20-one, 3α,5α-tetrahydroprogesterone, brexanoloneAllopregnanolone 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. | Drug | Allopregnanolone |
Primary outcome
California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score
Time frame: Baseline/pre-treatment and 14 weeks/post-treatment
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.
3 secondary outcomes
Behavioral Dyscontrol Scale - 2 (BDS-2) Total Score
Time frame: Baseline/pre-treatment and 14 weeks/post-treatment
CATSYS Dot-to-Dot Tremor Intensity (CATSYS DTD TI)
Time frame: Baseline/pre-treatment and 14 weeks/post-treatment
Hippocampal Volume, as Measured by Structural MRI
Time frame: Baseline/pre-treatment and 14 weeks/post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randi J Hagerman, MD principal investigator
UC Davis MIND Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allopregnanolone in people with Fragile X-associated Tremor/Ataxia Syndrome, run by Randi J. Hagerman, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
California Verbal Learning Test II (CVLT2) Trial 1-5 Free Recall Total Raw Score (time frame: Baseline/pre-treatment and 14 weeks/post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2018.