Metformin in Children With Fragile X Syndrome

Efficacy and Safety of Metformin in the Treatment of 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.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome; Metformin
• Intervention / Treatment: Drug: Metformin; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin group; The patients will be obtain Metformin starting from 50mg everyday to 1-2g per day for 6 months.	Drug: Metformin; 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.
Placebo Comparator: Placebo group; The patients will be obtain starch tablets starting from 50mg everyday to 1-2g per day for 6 months.	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of scores of Aberrant Behavior Checklist (ABC)	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.	From baseline to the 6th month

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University

Publications and helpful links

General Publications

• Zhu Y, Li D, Hu C, Tian Y, Lu P, Hagerman RJ, Xu X, Xu Q. Effects of Metformin on children with Fragile X Syndrome: a randomized, double-blind, placebo-controlled trial. Mol Autism. 2025 Nov 25;16(1):57. doi: 10.1186/s13229-025-00691-z.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2021
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 23, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Sex Chromosome Disorders; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Fragile X Syndrome; Organic Chemicals; Biguanides; Guanidines; Amidines; Metformin
• Other Study ID Numbers: FXS2021_1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No