Clinical trial NCT03722290: Metformin in Children and Adults With Fragile X Syndrome
Official title: Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fragile X Syndrome
Keywords: Metformin
Insulin signalisation
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: FRAXA Research Foundation
First posted: 2018-10-26
Enrollment: 15
Sex: ALL
Minimum age (years): 10
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of adverses events reported during the study
timeFrame: 9 weeks
measure: Change from baseline in the total score of the FX-normed Aberrant Behavior Checklist-Community after 9 weeks of metformin treatment
timeFrame: Baseline, Week 9
Secondary outcomes:
measure: Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)
timeFrame: Baseline, Week 9
measure: Level of synaptic plasticity using Electroencephalography (EEG)
timeFrame: Baseline, Week 9
measure: Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)
timeFrame: Baseline, Week 9
measure: Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)
timeFrame: Baseline, Week 9
measure: Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children
timeFrame: Baseline, Week 9
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Université de Sherbrooke
state: Quebec
Study officials:
References: