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.
a study on Fragile X Syndrome Mental Retardation, X Linked Trinucleotide Repeat Expansion Intellectual Disability Sex Chromosome Disorders
Summary
- Eligibility
- for people ages 6-25 (full criteria)
- Location
- at Sacramento, California and other locations
- Dates
- study startedcompletion
- Principal Investigator
- by Randi J Hagerman, MD
Description
Summary
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.
Official Title
A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome
Details
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.
Keywords
Fragile X Syndrome, Fragile X Mental Retardation Syndrome, Mental Retardation, X Linked, Genetic Diseases, X-Linked, Trinucleotide Repeat Expansion, Fra(X) Syndrome, Intellectual Disability, FXS, Neurobehavioral Manifestations, Sex Chromosome Disorders, Congenital Abnormalities, Metformin, Nervous System Diseases, Chromosome Disorders, X-Linked Mental Retardation, Inborn Genetic Diseases, X-Linked Genetic Diseases, Syndrome
Eligibility
You can join if…
Open to people ages 6-25
- Molecular genetic confirmation of the full FMR1 mutation or mosaicism.
- Males and non-pregnant, non-lactating females age 6 to 25 years, inclusive.
- Ability of subject and/or caregiver to understand, read, write, and speak English fluently to complete study-related materials.
- IQ ≤ 79 as measured by the Leiter-III at screening.
- Participant is able to speak at least occasional 3-word phrases.
- Participant and parent/caregiver are willing to participate in the protocol and able to attend the clinic regularly and reliably.
- Stable concomitant medication dose and dosing regimen for at least 4 weeks prior to the screening/baseline visit, and the intention to maintain a stable regimen of allowed concomitant medications for the full duration of the study.
- Stable behavioral/educational treatments for at least 4 weeks prior to the screening/baseline visit.
- Sexually active women of childbearing potential must be using a medically acceptable method of birth control for the duration of the study and have a negative urine pregnancy test collected at the initial screening/baseline visit.
- For participants who are not their own legal guardian, the parent/legal authorized representative is able to understand and sign an informed consent to participate in the study.
You CAN'T join if...
- Non-cooperation or inability to follow through with the study protocol.
- Life-threatening medical problem or other major systemic illness that compromises health or safety and/or would interfere with the study.
- History of intolerable adverse events with metformin.
- Current or recent metformin treatment (within the past year).
- Body mass index (BMI) less than 2 standard deviations for age.
- Serum creatinine > 1.4 mg/dl (female) or > 1.5 mg/dl (male) at screening.
- History of metabolic acidosis or a condition with lactic acidosis.
- Severe B12 deficiency.
- Pregnancy at screening or unwillingness to use acceptable method of birth control, if applicable.
Locations
- UC Davis MIND Institute
Sacramento California 95817 United States - University of Alberta
Edmonton Alberta T6G2R3 Canada - St Justine Hospital
Montréal Quebec H3T 1C5 Canada
Lead Scientist at UC Davis
- Randi J Hagerman, MD
Professor, MED: Pediatrics, School of Medicine. Authored (or co-authored) 604 research publications
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- Sponsor
- University of California, Davis
- Links
- Learn more or sign up for the study here! Sign up for this study
- ID
- NCT03479476
- Phase
- Phase 2/3 research study
- Study Type
- Interventional
- Participants
- About 120 people participating
- Last Updated
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