Metformin in Children With Fragile X Syndrome

This study is a controlled trial of metformin in children with fragile X syndrome(FXS). The age of FXS children range from 2 to 16 years old. Participants will be randomized in a double-blind design to either drug or placebo for 6-month period. The primary objectives are to assess metformin in treatment of behavior problems, cognitive and language with fragile X syndrome.

This is a single-center study at the Children's Hospital of Fudan University for FXS patients aged 2 to 16 years inclusive. It is a randomized, double-blind, placebo-controlled trial of metformin. Studies showed that there were pathogenically over activates of mTOR and MAPK/ERK pathways in FXS. Metformin, a guanidine derivative ,has been shown to reduce mTORC1 pathway activity in an AMPK-dependent manner and has also been shown to reduce MAPK pathway activity. Metformin treatments for FXS have been reported in animal experiments, some open label trials of metformin in FXS patients had been reported. Therefore, metformin has potential to rescue symptoms in children with FXS. In this study, researchers hope to investigate the improvement effect of metformin on FXS symptoms such as behavior problems, cognition, language. The intervention period is 6 months, follow-up visit at 1 year. The researchers will also assess the side effects of the study medication throughout the trial.

The patients in this group will be obtain Metformin starting from 50mg everyday at night, and gradually increase to maximum tolerable dose of 1-2g per day according to weights of patients for 6 months.

The patients in this group will be obtain starch tablets (which had same appearance and size comparing to Metformin) starting from 50mg everyday to 1-2g per day according to weights of patients for 6 months.

Difference on the scores of the ABC from baseline to the 6th month. ABC is a 58-item behavior scale ranked from 0("not a problem") to 3("severe problem") being the most severe for each item. 5 subscales include irritability, lethargy, stereotypy , hyperactivity and inappropriate speech. The same parent of patient will complete the checklist from baseline to 6th month. The global score changes of ABC will be measured as the primary outcome.

Inclusion Criteria: Genetic testing confirms the diagnosis of FXS Participate in the study with the informed consent of the guardian BMI>the 3rd percentile Not taking more than 2 therapeutic drugs Able to receive regular follow-up visits Exclusion Criteria: Malnutrition Primary heart disease Severe infection or acute clinical illness Gastrointestinal, renal, or hepatic disease Previous history of lactic acidosis previous use of metformin intolerant Use of angiotensin converting enzyme inhibitors, use of anticoagulants, vitamin B12 deficiency, alcohol consumption Unstable systemic diseases other than FXS Changes in clinical medication