Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
Overview
- Phase
- Phase 2
- Intervention
- Metformin
- Conditions
- Fragile X Syndrome
- Sponsor
- Université de Sherbrooke
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Incidence of adverses events reported during the study
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Çaku
Principal Investigator
Université de Sherbrooke
Eligibility Criteria
Inclusion Criteria
- •Aged between 10 et 45 years old
- •BMI \> 18.3
- •Molecular diagnosis of FXS
- •Accompanied by his legal tutor
Exclusion Criteria
- •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
Arms & Interventions
Metformin
Metformin 500mg twice a day per os for 9 weeks
Intervention: Metformin
Outcomes
Primary Outcomes
Incidence of adverses events reported during the study
Time Frame: 9 weeks
Number and severity of adverse events related to metformin treatment
Change from baseline in the total score of the FX-normed Aberrant Behavior Checklist-Community after 9 weeks of metformin treatment
Time Frame: Baseline, Week 9
The ABC-C is a 58-item caregiver-rated behavior scale where each item ranges from 0 (not a problem) to 3 (severe problem).
Secondary Outcomes
- Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)(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 score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children(Baseline, Week 9)
- Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)(Baseline, Week 9)