Metformin in Children and Adults With Fragile X Syndrome

Fragile X Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03722290
• Other study ID #: 2019-2797
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2018
• Est. completion date: November 1, 2020

Study information

• Verified date: February 2021
• Source: Université de Sherbrooke
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 1, 2020
• Est. primary completion date: October 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Fragile X Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Canada	Université de Sherbrooke	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Sherbrooke	FRAXA Research Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverses events reported during the study	Number and severity of adverse events related to metformin treatment	9 weeks
Primary	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	Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)	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	Baseline, Week 9
Secondary	Level of synaptic plasticity using Electroencephalography (EEG)	The effects of metformin on synaptic plasticity will be measured using the changes in amplitude of EEG waves	Baseline, Week 9
Secondary	Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)	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).	Baseline, Week 9
Secondary	Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)	The BRIEF is a 86-item questionary evaluating executive functions rated on a 3-point Likert scale: 1 (never), 2 (sometimes) and 3 (often).	Baseline, Week 9
Secondary	Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children	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.	Baseline, Week 9