A Trial of Metformin in Individuals With Fragile X Syndrome (Met)

Inclusion Criteria:

• Subject has Fragile X syndrome with a molecular genetic confirmation of the fullFMR1 mutation (>200 CGG repeats) or the other loss of function mutations of the FMR1gene (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 birthcontrol for the duration of the study. Acceptable forms of birth control includeabstinence (only for subjects who are not sexually active), intrauterine devices inplace for at least 3 months, oral contraceptives, surgical sterilization, oradequate barrier methods.

• Subject must have a caregiver (parent, guardian, or other legally authorizedrepresentative) 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 speakEnglish or French fluently to complete study-related materials.

• For subjects who are not their own legal guardian, subject's caregiver is able tounderstand and sign an informed consent to participate in the study.

• The use of concomitant medication must be stable, in terms of dose and dosingregimen, for at least 4 weeks prior to Screening and must remain stable during theperiod between first visit (Screening) and the commencement of the study; everyeffort should be made to maintain stable regimens of allowed concomitant medicationsfrom the time of commencement of double-blind study medication until the last studyassessment.

• Behavioral/educational treatments must be stable for 4 weeks prior to first visit (Screening) and must remain stable during the period between Screening and thecommencement of randomized double-blind study medication.

10. Overall age equivalent is not higher than 13 and IQ is not higher than 85, asassessed at Screening on the Leiter-III, and subject must speak at leastoccasional 3-word phrases.

Exclusion Criteria:

• Families that are not cooperative and will not follow through with the demands ofthis study.

• Subject has a life-threatening medical problem or other major systemic illness thatcompromises 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 HealthOrganization 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.