Clinical Trial of Metformin in Individuals with Fragile X Syndrome (FXS)

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

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Objectives

  1. Assess safety and tolerability of metformin in individuals with FXS ages 6 to 25 who are treated over a 4-month period.

  2. Assess the benefit of Metformin in the treatment of language deficits, behavior problems, and obesity/excessive appetite in individuals with FXS over a 4-month period.

  3. Assess the utility of innovative outcome measures, including measures of brain processing.

  4. Assess molecular biomarkers that may predict which patients may be likely to benefit from Metformin treatment.

 

Inclusion and Exclusion Criteria

Inclusion criteria: A subject will be eligible for study participation if subject meets all following criteria:

  1. Subject has Fragile X syndrome with a molecular genetic confirmation of the full FMR1 mutation (>200 CGG repeats).

  2. Subject is a male or non-pregnant, non-lactating female age 6 to 25 years, inclusive.

  3. 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.

  4. Subject must have a parent or caretaker who is willing to participate in the whole study.

  5. Subject and caregiver are able to attend the clinic regularly and reliably.

  6. Subject and/or subject’s parent/legal authorized representative is able to understand, read, write and speak English or French fluently to complete study-related materials.

  7. For subjects who are not their own legal guardian, subject’s parent/legal authorized representative is able to understand and sign an informed consent to participate in the study.

  8. 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.

  9. 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 IQ, as assessed at Screening on the Leiter-III, is not higher than 79, and subject must speak at least occasional 3-word phrases.

Exclusion criteria

  1. Families who are not cooperative and will not follow through with the demands of this study.

  2. Subject has a life-threatening medical problem or other major systemic illness that compromises health or safety and/or would interfere with this study.

  3. Age younger than 6 or older than 25 years.

  4. History of intolerable adverse events with Metformin.

  5. Current or recent Metformin treatment (within the past year).

  6. BMI less than 2 standard deviations for age using the World Health Organization scale.

  7. Serum creatinine > 1.4 mg/dl (female) or > 1.5 mg/dl (male).

  8. History of metabolic acidosis or a condition with lactic acidosis.

  9. Vitamin B12 deficiency.

  10. Pregnancy at screening or unwillingness to use acceptable method of birth control, if applicable.

  11. IQ higher than 79 on the Leiter-III at Screening.

 

Study Timelines

The study plans to enroll 60 participants over a 3-year period at each site. Approximately 20 patients per year with FXS will be randomized at each site to receive either metformin or placebo for a 4-month period. During the 4-month study period, subjects will attend three visits to the recruiting site: screening/baseline, 2-month, and 4-month visits. In addition, routine phone calls will be made once per week during the first month of the study, and once at Week 12/Month 3.



Further Materials

Further information for families: Metformin Study Summary