Fragile X SyndromeEarly Phase 1NCT02998151

Neurophysiological and Acute Pharmacological Studies in FXS Patients

A Early Phase 1 study testing Acamprosate, Lovastatin and Minocycline in people with Fragile X Syndrome, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim of this study is to utilize neurophysiologic assessments, behavioral measures and clinical measures to assess how much deficits associated with Fragile X Syndrome from pre-dose to post-dose using pharmacology. Read more about this study

Who is it for?: Ages 15 to 55 years
Conditions the study is for: Fragile X Syndrome
What is being tested?: Acamprosate, Lovastatin and Minocycline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 1 siteUnited States
Study dates: Jan 2016to Nov 2020
Phase: Early Phase 1
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 15 to 55 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). FXS is defined as full FMR1 mutations (>200 CGG repeats) confirmed by genetic testing.
General good health as determined by physical exam, medical history and laboratory work up.

Who cannot join

Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline will be excluded.
Subjects will also be excluded if they have taken any investigational drug within 3 months, have a history of substance abuse or dependence within 6 months, or significant psychiatric or central nervous system neurological disease unrelated to FXS.
Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and benzodiazepines and are exclusions (within 5 half-lives). Those taking other psychiatric medications must be on stable doses for 4 weeks before any testing.
For female subjects of child bearing potential, a positive urine pregnancy test.
Potential subjects with a creatinine clearance < 50 mL/min will be excluded.
Identified medical issues, inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229

Other trials in United States

About this study

Conditions: Fragile X Syndrome
Being tested: Acamprosate, Lovastatin, Minocycline, Placebo, Baclofen
Medical subject headings: Fragile X Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AcamprosateDrug
two 666mg pills
LovastatinDrug
two 20mg pills
MinocyclineDrug
two 135mg pills
PlaceboDrug
placebo pill
BaclofenDrug
one 30mg pill

Study groups in NCT02998151
Study group	Role	What they receive
All Study Participants	Experimental	Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed. Receives: Drug: Acamprosate; Drug: Lovastatin; Drug: Minocycline; Drug: Placebo; Drug: Baclofen

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in EEG Relative Gamma Power
EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.
Measured: Pre-dose, 4-hour post-dose
Clinical Global Impressions-Improvement
The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
Measured: 4-hour post-dose

Secondary outcomes (3)

Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).
Measured: 4-hour post-dose
Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.
Measured: Pre-dose, 4-hour post dose
Test of Attentional Performance for Children (KiTAP) Test of Alertness
Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.
Measured: Predose, 4-hour post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2016Nov 2020

First posted20 Dec 2016 (estimated)
Study startJan 2016
Primary completionNov 2020
Study completionNov 2020

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
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: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02998151
Sponsor's protocol ID: CIN001 - {LAM}
Other IDs: U54HD082008
Status last verified: Nov 2021
First submitted: 1 Dec 2016
Last updated: 26 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated device: No

Publications

Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord. 2022 Sep 27;14(1):52. doi: 10.1186/s11689-022-09455-9.
PubMed 36167501

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Aggressive Behavior in Fragile X Syndome
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
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Single Session Support for Parents of Children With Neurodevelopmental Disabilities Struggling With Anxious Avoidance
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RecruitingObservational study
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Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
Not yet recruitingPhase 2/3
A Study to Investigate the Effects and Safety of Codabakalner for the Treatment of FXS in Male Participants and Adult Participants With ADS
Fragile X Syndrome (FXS), Autism Spectrum Disorder (ASD)

All Fragile X Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neurophysiological and Acute Pharmacological Studies in FXS Patients
ClinicalTrials.gov ID: NCT02998151
Acronym / sponsor ID: CIN001 - {LAM}
Conditions: Fragile X Syndrome
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Jan 2016
Primary completion: Nov 2020 (actual)
Study completion: Nov 2020 (actual)
First posted: 20 Dec 2016 (estimated)
Results: Posted 24 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 1
Model description: This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.

Arm	Type	Receives
All Study Participants	Experimental	Drug: Acamprosate, Drug: Lovastatin, Drug: Minocycline, Drug: Placebo, Drug: BaclofenParticipants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.

Who may qualify

Ages: 15 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (2 listed)

Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled "Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). FXS is defined as full FMR1 mutations (>200 CGG repeats) confirmed by genetic testing.
General good health as determined by physical exam, medical history and laboratory work up.

Key exclusion criteria (6 listed)

Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline will be excluded.
Subjects will also be excluded if they have taken any investigational drug within 3 months, have a history of substance abuse or dependence within 6 months, or significant psychiatric or central nervous system neurological disease unrelated to FXS.
Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and benzodiazepines and are exclusions (within 5 half-lives). Those taking other psychiatric medications must be on stable doses for 4 weeks before any testing.
For female subjects of child bearing potential, a positive urine pregnancy test.
Potential subjects with a creatinine clearance < 50 mL/min will be excluded.

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
Acamprosatetwo 666mg pills	Drug	All Study Participants
Lovastatintwo 20mg pills	Drug	All Study Participants
Minocyclinetwo 135mg pills	Drug	All Study Participants
Placeboplacebo pill	Drug	All Study Participants
Baclofenone 30mg pill	Drug	All Study Participants

Primary outcome

Change in EEG Relative Gamma Power
Time frame: Pre-dose, 4-hour post-dose
EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.
Clinical Global Impressions-Improvement
Time frame: 4-hour post-dose
The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).

3 secondary outcomes

Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
Time frame: 4-hour post-dose
Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
Time frame: Pre-dose, 4-hour post dose
Test of Attentional Performance for Children (KiTAP) Test of Alertness
Time frame: Predose, 4-hour post-dose

Results and safety

Results posted to the registry on 24 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Study Participants	29	5

Primary outcome: Change in EEG Relative Gamma Power

Time frame: Pre-dose, 4-hour post-dose. Mean (Standard Deviation). Unit: percent of power in gamma frequencies

Measure	Placebo n = 26	Acamprosate n = 16	Lovastatin n = 28	Minocycline n = 27	Baclofen n = 18
Value	0.0024 (.0265)	-0.0077 (0.0252)	-0.0039 (0.0225)	0.0019 (0.0235)	-0.0160 (0.0346)

Population analysed: Missing 1 placebo, 1 lovastatin who contributed data with excessive movement or other artifact, or were unable to complete the task.

Primary outcome: Clinical Global Impressions-Improvement

Time frame: 4-hour post-dose. Mean (Standard Deviation). Unit: score on a scale

Measure	Placebo n = 27	Acamprosate n = 16	Lovastatin n = 29	Minocycline n = 26	Baclofen n = 17
Value	3.70 (.61)	3.88 (.62)	3.97 (.50)	3.81 (.49)	3.94 (.43)

Population analysed: CGI-I was not collected for one participant on their minocycline day and another participant on their baclofen day.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected up to four weeks after the final dosing visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 27 (0%)	3 of 27 (11.1%)	0 of 27
Acamprosate	0 of 16 (0%)	7 of 16 (43.8%)	0 of 16
Lovastatin	0 of 29 (0%)	4 of 29 (13.8%)	0 of 29
Minocycline	0 of 27 (0%)	4 of 27 (14.8%)	0 of 27
Baclofen	0 of 18 (0%)	4 of 18 (22.2%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36167501Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord. 2022 Sep 27;14(1):52. doi: 10.1186/s11689-022-09455-9.

Related trials for Fragile X Syndrome

Not yet recruitingPhase 2
Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
Aggressive Behavior in Fragile X Syndome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruiting
Single Session Support for Parents of Children With Neurodevelopmental Disabilities Struggling With Anxious Avoidance
Neurodevelopmental Disorders, Autism Spectrum Disorder (ASD)
RecruitingObservational study
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
Not yet recruitingPhase 2/3
A Study to Investigate the Effects and Safety of Codabakalner for the Treatment of FXS in Male Participants and Adult Participants With ADS
Fragile X Syndrome (FXS), Autism Spectrum Disorder (ASD)

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.

Craig A Erickson, M.D. principal investigator

Children's Hospital Medical Center, Cincinnati

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Acamprosate, Lovastatin and Minocycline in people with Fragile X Syndrome, run by Children's Hospital Medical Center, Cincinnati 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 6 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 26 Nov 2021. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 24 Nov 2021). 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?

Change in EEG Relative Gamma Power (time frame: Pre-dose, 4-hour post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02998151, which also lists 1 linked publication.

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 26 Nov 2021.