Metformin in Children and Adults With Fragile X Syndrome

Sponsor

Université de Sherbrooke (Other)

Overall Status

Completed

CT.gov ID

NCT03722290

Collaborator

FRAXA Research Foundation (Other)

Enrollment

Location

Arm

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fragile X Syndrome	Drug: Metformin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open-label trialOpen-label trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study

Actual Study Start Date :

Sep 1, 2018

Actual Primary Completion Date :

Oct 24, 2019

Actual Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin Metformin 500mg twice a day per os for 9 weeks	Drug: Metformin Oral administration of metformin 250mg (twice a day) for the 1st week followed by metformin 500mg (twice a day) for the next 8 weeks. Other Names: Glucophage

Arm

Intervention/Treatment

Experimental: Metformin

Metformin 500mg twice a day per os for 9 weeks

Drug: Metformin

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

Other Names:

Glucophage

Outcome Measures

Primary Outcome Measures

Incidence of adverses events reported during the study [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 [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 Outcome Measures

Level of cortical excitability using Transcranial Magnetic Stimulation (TMS) [Baseline, Week 9]
The effects of metformin on cortical excitability will be measured using a magnetic stimulation on the primary motor cortex to assess intracortical facilitation and inhibition
Level of synaptic plasticity using Electroencephalography (EEG) [Baseline, Week 9]
The effects of metformin on synaptic plasticity will be measured using the changes in amplitude of EEG waves
Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C) [Baseline, Week 9]
Determining if metformin lowers the score of each subscale of the ABC-C: Irritability (18 items), hyperactivity (10 items), lethargy (16 items), social avoidance (4 items), stereotypy (6 items) and inappropriate speech (4 items). Each item is scored from 0 (not a problem) to 3 (severe problem).
Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF) [Baseline, Week 9]
The BRIEF is a 86-item questionary evaluating executive functions rated on a 3-point Likert scale: 1 (never), 2 (sometimes) and 3 (often).
Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children [Baseline, Week 9]
KiTAP is a computerized continuous test of attention assessing the ability to maintain attention in the presence of distractors. The 4 subtests used are Alertness reaction time, Distractibility commission errors, Go/No-Go commission errors and Flexibility errors.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 45 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Université de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5H3

Sponsors and Collaborators

Université de Sherbrooke
FRAXA Research Foundation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Çaku, Principal Investigator, Université de Sherbrooke

ClinicalTrials.gov Identifier:

NCT03722290

Other Study ID Numbers:

2019-2797

First Posted:

Oct 26, 2018

Last Update Posted:

Feb 4, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Çaku, Principal Investigator, Université de Sherbrooke

Metformin

Insulin signalisation

Additional relevant MeSH terms:

Fragile X Syndrome

Syndrome

Metformin

Study Results

No Results Posted as of Feb 4, 2021