Metformin in Children and Adults With Fragile X Syndrome

NCT03722290 | Completed Phase 2

• 1 other identifier: 2019-2797
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Fragile X Syndrome (FXS) is caused by loss of FMR1 expression on the X chromosome that leads to increased mRNA translation, which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rifampicin complex 1) signalling and consequently in synaptic dysfunction and neurological development. There is presently no cure for FXS. Recent studies suggest that metformin (a widely prescribed drug for type II diabetes in children and adults) which crosses the blood-brain barrier, corrects various neurological and behavioral FXS phenotypes by normalizing ERK signaling, EIF4E phosphorylation and lowering expression of MMP9 to normal. Since this drug has not been previously used specifically for treatment of FXS (only few cases reported), the investigators propose an open-label trial of metformin in children and adults with FXS to better understand the safety and efficacy in both behavior and cognition.

Conditions

Fragile X Syndrome

Keywords

Metformin; Insulin signalisation

Outcome Measures

Primary Outcomes (2)

• Incidence of adverses events reported during the study

  Number and severity of adverse events related to metformin treatment

  9 weeks

• Change from baseline in the total score of the FX-normed Aberrant Behavior Checklist-Community after 9 weeks of metformin treatment

  The ABC-C is a 58-item caregiver-rated behavior scale where each item ranges from 0 (not a problem) to 3 (severe problem).

  Baseline, Week 9

Secondary Outcomes (5)

• Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)

  Baseline, Week 9

• Level of synaptic plasticity using Electroencephalography (EEG)

  Baseline, Week 9

• Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)

  Baseline, Week 9

• Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)

  Baseline, Week 9

• Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children

  Baseline, Week 9

Study Arms (1)

Metformin

EXPERIMENTAL

Metformin 500mg twice a day per os for 9 weeks

Drug: Metformin

Interventions

Metformin DRUG

Oral administration of metformin 250mg (twice a day) for the 1st week followed by metformin 500mg (twice a day) for the next 8 weeks.

Also known as: Glucophage

Metformin

Eligibility Criteria

• Age: 10 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged between 10 et 45 years old
• BMI \> 18.3
• Molecular diagnosis of FXS
• Accompanied by his legal tutor

You may not qualify if:

• Pregnancy/Breastfeeding
• Intolerance to metformin
• History of lactic acidosis
• Gastric/renal/hepatic pathology
• Acute medical condition
• Concomitant use of ACE inhibitors
• Modification of antipsychotic treatments in the last 6 weeks

Sponsors & Collaborators

• Université de Sherbrooke: lead
• FRAXA Research Foundation: collaborator

Study Sites (1)

Université de Sherbrooke

Sherbrooke, Quebec, J1H 5H3, Canada

Location

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open-label trial

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 26, 2018
• Study Start: September 1, 2018
• Primary Completion: October 24, 2019
• Study Completion: November 1, 2020
• Last Updated: February 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)