Metformin in Children and Adults With Fragile X Syndrome

Université de Sherbrooke

Status and phase: Completed; Phase 2

Conditions: Fragile X Syndrome

Treatments: Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT03722290

2019-2797

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 10 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Metformin

Experimental group

Description:

Metformin 500mg twice a day per os for 9 weeks

Treatment:

Drug: Metformin