Fragile X SyndromePhase 1/2NCT04141163
Metformin in Patients With Fragile X
A Phase 1/2 study testing Metformin in people with Fragile X Syndrome, run by Rowan University at 1 site in United States.
Trial summary
The purpose of this trial is to investigate the use of metformin in the treatment of Fragile X syndrome (FXS) patients. Metformin is an FDA approved compound with an established safety profile and minimal side effects that specifically targets and normalizes multiple aspects of the pathophysiology in FXS. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men only
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2019to Mar 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 to 50 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Male between the ages of 16-50 years old at the time of consent
- Diagnosis of full mutation FXS.
- Stable on any psychoactive medication for at least 4 weeks before receiving study drug, including antidepressants, stimulants, antipsychotics, and mood stabilizers.
- Seizure free for at least the past 3 months.
- No major health issues or diseases expected to interfere with the study
- No history of diabetes
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- Not currently taking metformin at the time of enrollment
- Average basal blood glucose HgbA1c < 7.0
- Study partner with frequent contact with patient willing to accompany patient to visits and complete caretaker/partner study forms
- No contraindication to metformin
- Willing to complete all baseline assessments and study procedures
Who cannot join
- Has a medical condition that would make treatment unsafe such as diabetes, pancreatic disease, liver or kidney disease, a history of epilepsy or seizure disorder that is not controlled, as well as any other medical condition as determined by the study doctor.
- Has an eating disorder that has been clinically diagnosed, predisposing them to low BMI.
- Has received any investigational compound within 30 days prior to the first dose of study medication.
- Has received metformin in a previous clinical study or as a therapeutic agent.
- Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress.
- Has uncontrolled, clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
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- Has a known hypersensitivity to any component of the formulation of metformin.
- Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 6 months prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
- Currently taking any excluded medication, supplements, or food products, or has taken any in the 3 weeks preceding Visit 1. This includes carbonic anhydrase inhibitors and the medication topamax.
- Has evidence of current cardiovascular, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking metformin or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to uncontrolled seizure disorders, and cardiac arrhythmias.
- History of any surgical intervention known to impact absorption (e.g., bariatric surgery or bowel resection).
- Compromised renal function at screening as determined by creatinine levels >1.5mg/dL and/or creatinine clearance <45mL/min based on Cockcroft-Gault calculation.
- Liver dysfunction at screening as evidenced by alanine transaminase (ALT/SGPT) values > 2X upper limit of normal or aspartate transaminase (AST/SGOT) values > 3X upper limit of normal or total bilirubin > 2X upper limit of normal.
- Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1.
- Has a history of abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator.
- Has abnormal Screening or Day 1 vital sign values that suggest a clinically significant underlying disease.
- Is at risk of suicide, has made a suicide attempt within the last year or has current active suicidal ideation. In accordance with previous FDA regulated studies on patients with FXS this determination will include asking 3 questions. 1) Has the subject made a suicide attempt? 2) Has the subject expressed any (active) suicidal thoughts or intent to harm him/herself or others? 3) Has there been a significant increase in the severity or frequency of self-injurious behaviors, or harm toward others, such that continued safety is a concern?
- Laboratory abnormalities in B12, or other common lab parameters that might contribute to cognition or participation in study
- In the opinion of the investigator or sponsor, the participant is unsuitable for inclusion in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Rowan University School of Osteopathic Medicine
Stratford, New Jersey, 08084
Lauren Fedor, 856-566-6003, fedor@rowan.edu
About this study
Official title: A Parallel Group Design Randomized Double-Blind Trial of Metformin Treatment in Patients With Fragile X Syndrome on Safety and Effects on Cognition, Anxiety, Attention and Biomarkers
The purpose of this trial is to investigate the use of metformin in the treatment of Fragile X syndrome (FXS) patients. Metformin is an FDA approved compound with an established safety profile and minimal side effects that specifically targets and normalizes multiple aspects of the pathophysiology in FXS. This is a randomized double-blind placebo-controlled 2-arm parallel group design study of the drug metformin and placebo in FXS subjects with a primary outcome measure of safety/tolerability and secondary outcome measures on cognition, attention, anxiety, sleep, and physiologic and biochemical biomarkers.
Read the detailed description
This trial will be a randomized placebo controlled, double-blind, parallel group design study of treatment with metformin on the primary outcome of safety/tolerance with secondary outcome measurements of the effects on cognition (encompassing social and repetitive behavior), attention, anxiety, and physiological and biochemical biomarkers of patients with FXS. FXS represents a well-defined population of ASD in which to test a specific targeted treatment looking at a well-defined set of cognitive and bioassay measures.
Trial length is designed to have a chance at seeing if the medication can improve cognitive outcome measures. The study duration includes the screening period and a 24-week single-blind drug/placebo phase.
- Conditions
- Fragile X Syndrome
- Being tested
- Metformin, Placebo oral tablet
- 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.
MetforminDrug
Also called glucophage
Metformin, 1,1 dimethylbiguanide, or systematic (IUPAC) name N,N-dimethylimidodicarbonimidic diamide, is an oral anti-diabetic medicine approved in the US by the FDA in 1994. It is marketed alone under the names metformin (generic), Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, and Diaformin and in combination with other drugs under the names Actoplus Met, Metaglip, Glucovance, Janumet, Kombiglyze XR, and PrandiMet
Placebo oral tabletDrug
No therapeutic effect
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Subjects randomized to metformin will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day. Receives: Drug: Metformin |
| Placebo | Placebo comparator | Subjects randomized to placebo will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety and tolerability of metformin in patients with Fragile X Syndrome as assessed by the number of adverse events reported during the course of the study.
measured by the number of reported adverse events, assessed using the Safety Monitoring Uniform Report Form (SMURF), modified for metformin use
Measured: 1-2 years
Secondary outcomes (1)
Patients taking Metforming have improved cognition, sleep, attention or anxiety from baseline to the end of the study
measured by a variety of questionnaires and assessments done throughout the length of the study
Measured: 1-2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study start29 Oct 2019
- Primary completionMar 2021 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fragile X 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rowan University
- Sponsor type
- University, hospital or other
- Collaborators
- FRAXA Research Foundation, University of Pennsylvania
- Responsible party
- Principal investigator, Sean McBride, M.D., Ph.D., Rowan University
- Investigators
- Sean McBride, MD, PhD, Principal investigator, Rowan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04141163
- Sponsor's protocol ID
- Pro2018000310
- Status last verified
- Oct 2019
- First submitted
- 24 Oct 2019
- Last updated
- 31 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Parallel Group Design Randomized Double-Blind Trial of Metformin Treatment in Patients With Fragile X Syndrome on Safety and Effects on Cognition, Anxiety, Attention and Biomarkers
- ClinicalTrials.gov ID
- NCT04141163
- Acronym / sponsor ID
- Pro2018000310
- Conditions
- Fragile X Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Rowan UniversityUniversity, hospital or other
- Collaborators
- FRAXA Research Foundation, University of Pennsylvania
- Study start
- 29 Oct 2019 (actual)
- Primary completion
- Mar 2021 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 28 Oct 2019 (actual)
- Results
- Not posted in the source record
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 trial is to investigate the use of metformin in the treatment of Fragile X syndrome (FXS) patients. Metformin is an FDA approved compound with an established safety profile and minimal side effects that specifically targets and normalizes multiple aspects of the pathophysiology in FXS. This is a randomized double-blind placebo-controlled 2-arm parallel group design study of the drug metformin and placebo in FXS subjects with a primary outcome measure of safety/tolerability and secondary outcome measures on cognition, attention, anxiety, sleep, and physiologic and biochemical biomarkers.
Detailed description
This trial will be a randomized placebo controlled, double-blind, parallel group design study of treatment with metformin on the primary outcome of safety/tolerance with secondary outcome measurements of the effects on cognition (encompassing social and repetitive behavior), attention, anxiety, and physiological and biochemical biomarkers of patients with FXS. FXS represents a well-defined population of ASD in which to test a specific targeted treatment looking at a well-defined set of cognitive and bioassay measures.
Trial length is designed to have a chance at seeing if the medication can improve cognitive outcome measures. The study duration includes the screening period and a 24-week single-blind drug/placebo phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminSubjects randomized to metformin will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day. |
| Placebo | Placebo comparator | Drug: Placebo oral tabletSubjects randomized to placebo will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Male between the ages of 16-50 years old at the time of consent
- Diagnosis of full mutation FXS.
- Stable on any psychoactive medication for at least 4 weeks before receiving study drug, including antidepressants, stimulants, antipsychotics, and mood stabilizers.
- Seizure free for at least the past 3 months.
- No major health issues or diseases expected to interfere with the study
Key exclusion criteria (19 listed)
- Has a medical condition that would make treatment unsafe such as diabetes, pancreatic disease, liver or kidney disease, a history of epilepsy or seizure disorder that is not controlled, as well as any other medical condition as determined by the study doctor.
- Has an eating disorder that has been clinically diagnosed, predisposing them to low BMI.
- Has received any investigational compound within 30 days prior to the first dose of study medication.
- Has received metformin in a previous clinical study or as a therapeutic agent.
- Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress.
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 |
|---|---|---|
| MetforminAlso: glucophageMetformin, 1,1 dimethylbiguanide, or systematic (IUPAC) name N,N-dimethylimidodicarbonimidic diamide, is an oral anti-diabetic medicine approved in the US by the FDA in 1994. It is marketed alone under the names metformin (generic), Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, and Diaformin and in combination with other drugs under the names Actoplus Met, Metaglip, Glucovance, Janumet, Kombiglyze XR, and PrandiMet | Drug | Metformin |
| Placebo oral tabletNo therapeutic effect | Drug | Placebo |
Primary outcome
The safety and tolerability of metformin in patients with Fragile X Syndrome as assessed by the number of adverse events reported during the course of the study.
Time frame: 1-2 years
measured by the number of reported adverse events, assessed using the Safety Monitoring Uniform Report Form (SMURF), modified for metformin use
1 secondary outcome
Patients taking Metforming have improved cognition, sleep, attention or anxiety from baseline to the end of the study
Time frame: 1-2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2019.
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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.
Sean McBride, MD, PhD principal investigator
Rowan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Metformin in people with Fragile X Syndrome, run by Rowan University 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 11 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 31 Oct 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lauren Fedor (856-566-6003, fedor@rowan.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety and tolerability of metformin in patients with Fragile X Syndrome as assessed by the number of adverse events reported during the course of the study. (time frame: 1-2 years). 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 31 Oct 2019.