Testing metformin for treating fragile X syndrome

A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS)

This study is testing if metformin can help improve language skills, behavior, and weight in young people with fragile X syndrome.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 6 Years to 35 Years
• Sex: All
• Sponsor: University of Alberta (Academic / other)
• Locations: 2 sites (Edmonton, Alberta and 1 other locations)
• Trial ID: NCT03862950 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effects of metformin on individuals aged 6 to 35 with fragile X syndrome. Participants will be randomly assigned to receive either metformin or a placebo in a double-blind manner. Over a four-month period, they will attend three visits for assessments of safety, tolerability, and efficacy, focusing on language deficits, behavioral issues, and obesity. The study aims to explore how metformin may normalize disrupted signaling pathways in the central nervous system associated with fragile X syndrome.

Who should consider this trial

Good fit: Ideal candidates are males or non-pregnant females aged 6 to 35 with a confirmed diagnosis of fragile X syndrome.

Not a fit: Patients outside the age range or those with other genetic conditions unrelated to fragile X syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve language skills, behavior, and weight management in patients with fragile X syndrome.

How similar studies have performed: Previous studies have shown promising results using metformin in individuals with fragile X syndrome, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Subject has Fragile X syndrome with a molecular genetic confirmation of the full FMR1 mutation (\>200 CGG repeats) or the other loss of function mutations of the FMR1 gene (SNVs and deletions of the gene).
* Subject is a male or non-pregnant, non-lactating female age 6 through 35 years, inclusive.
* Subjects who are capable of becoming pregnant must use an acceptable method of birth control for the duration of the study. Acceptable forms of birth control include abstinence (only for subjects who are not sexually active), intrauterine devices in place for at least 3 months, oral contraceptives, surgical sterilization, or adequate barrier methods.
* Subject must have a caregiver (parent, guardian, or other legally authorized representative) who is willing to participate in the whole study.
* Subject and caregiver are able to attend the clinic regularly and reliably.
* Subject and/or subject's caregiver is able to understand, read, write and speak English or French fluently to complete study-related materials.
* For subjects who are not their own legal guardian, subject's caregiver is able to understand and sign an informed consent to participate in the study.
* The use of concomitant medication must be stable, in terms of dose and dosing regimen, for at least 4 weeks prior to Screening and must remain stable during the period between first visit (Screening) and the commencement of the study; every effort should be made to maintain stable regimens of allowed concomitant medications from the time of commencement of double-blind study medication until the last study assessment.
* Behavioral/educational treatments must be stable for 4 weeks prior to first visit (Screening) and must remain stable during the period between Screening and the commencement of randomized double-blind study medication.
* 10. Overall age equivalent is not higher than 13 and IQ is not higher than 85, as assessed at Screening on the Leiter-III, and subject must speak at least occasional 3-word phrases.

Exclusion Criteria:

* Families that are not cooperative and will not follow through with the demands of this study.
* Subject has a life-threatening medical problem or other major systemic illness that compromises health or safety and/or would interfere with this study.
* Age younger than 6 or older than 35 years.
* History of intolerable adverse events with metformin.
* Current or recent metformin treatment (within the past 4-months).
* BMI inferior to 2 standard deviations below the mean for age using the World Health Organization scale.
* Serum creatinine \> 1.4 mg/dl (female) or \> 1.5 mg/dl (male).
* History of metabolic acidosis or a condition with lactic acidosis.
* Severe Vitamin B12 deficiency.
* Pregnancy at screening or unwillingness to use acceptable method of birth control, if applicable.
* Age equivalent higher than 13 or IQ higher than 85 on the Leiter-III at Screening.

Where this trial is running

Edmonton, Alberta and 1 other locations

• University of Alberta — Edmonton, Alberta, Canada (Recruiting)
• CHU Sainte-Justine — Montreal, Quebec, Canada (Not_yet_recruiting)

Study contacts

• Principal investigator: Francois Bolduc, MD — University of Alberta
• Study coordinator: Research Coordinator

Conditions Fragile X Syndrome; Fragile X Mental Retardation Syndrome; Mental Retardation, X-Linked; Genetic Diseases, X-Linked; Trinucleotide Repeat Expansion; Fra Syndrome; Intellectual Disability; FXS