A Study of Experimental Treatment With Metformin for Fragile X Syndrome

Learn if Metformin may be helpful for language, behavior problems, and obesity / excessive appetite in patients with Fragile X Syndrome.

This study is a controlled trial of metformin in individuals with fragile X syndrome between the ages of 6 and 25 years. Participants will be randomized in a double-blind design to either drug or placebo and will attend three visits to the study site in a 4-month period for a series of tests. The primary objectives are to assess safety, tolerability, and efficacy of metformin in the treatment of language deficits, behavior problems, and obesity/excessive appetite in individuals with fragile X syndrome.

This is a multi-site study for fragile X syndrome (FXS) patients aged 6 to 25 years inclusive. It is a randomized, double-blind, placebo-controlled trial of metformin (also known as Glumetza, Glucophage, Fortamet), a type 2 diabetes medication that can also improve obesity and excessive appetite.

Metformin has emerged as a candidate drug for the targeted treatment of FXS based on animal studies showing rescue of multiple phenotypes in the FXS model. Metformin may contribute to normalizing signaling pathways in FXS in the central nervous system, which may include activities of mTOR and PI3K, both of which have shown to be pathogenically overactive in FXS. In addition, metformin inhibits phosphodiesterase, which would lead to correction of cAMP levels, and MMP9 production, which is also elevated in FXS. Looking at the potential signaling pathways, metformin appears to be a good candidate for targeting several of the intracellular functions in neurons disrupted in FXS and, therefore, has potential to rescue several types of symptoms in individuals with FXS. The researchers have utilized metformin in the clinical treatment of over 20 individuals with FXS between the ages of 4 and 58 years and have found the medication to be well tolerated and to provide benefits not only in lowering weight gain and normalizing appetite but also in language and behavior. In this controlled trial, the researchers hope to further assess metformin's safety and benefits in the areas of language and cognition, eating and weight loss, and overall behavior.

Each participant will be involved in this trial for a period of 4 months. This will include 3 visits to the UC Davis MIND Institute and 5 phone calls. At each visit, the researchers will assess behavioral, cognitive, and language development. The researchers will also assess the side effects of the study medication throughout the trial.

Study record updated 9/26/2018 to reflect the following IRB-approved protocol modifications: Erroneous references to "digital" books for primary outcome measure were removed, as this measure is administered using print (non-digital) materials. Eligibility criteria were updated to include subjects with IQ of up to and including 79 on the Leiter-III at screening. The Hyperphagia Questionnaire (HQ-CT) was replaced by the Anxiety Depression and Mood Screen (ADAMS) as a secondary outcome measure.