search
Back to results

Metformin in Children and Adults With Fragile X Syndrome

Primary Purpose

Fragile X Syndrome

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Sponsored by
Université de Sherbrooke
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fragile X Syndrome focused on measuring Metformin, Insulin signalisation

Eligibility Criteria

10 Years - 45 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Université de Sherbrooke

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin

Arm Description

Metformin 500mg twice a day per os for 9 weeks

Outcomes

Primary Outcome Measures

Incidence of adverses events reported during the study
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
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)
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)
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)
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)
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
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.

Full Information

First Posted
October 24, 2018
Last Updated
February 1, 2021
Sponsor
Université de Sherbrooke
Collaborators
FRAXA Research Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT03722290
Brief Title
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

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
October 24, 2019 (Actual)
Study Completion Date
November 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Université de Sherbrooke
Collaborators
FRAXA Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
Keywords
Metformin, Insulin signalisation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin 500mg twice a day per os for 9 weeks
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Intervention Description
Oral administration of metformin 250mg (twice a day) for the 1st week followed by metformin 500mg (twice a day) for the next 8 weeks.
Primary Outcome Measure Information:
Title
Incidence of adverses events reported during the study
Description
Number and severity of adverse events related to metformin treatment
Time Frame
9 weeks
Title
Change from baseline in the total score of the FX-normed Aberrant Behavior Checklist-Community after 9 weeks of metformin treatment
Description
The ABC-C is a 58-item caregiver-rated behavior scale where each item ranges from 0 (not a problem) to 3 (severe problem).
Time Frame
Baseline, Week 9
Secondary Outcome Measure Information:
Title
Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)
Description
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
Time Frame
Baseline, Week 9
Title
Level of synaptic plasticity using Electroencephalography (EEG)
Description
The effects of metformin on synaptic plasticity will be measured using the changes in amplitude of EEG waves
Time Frame
Baseline, Week 9
Title
Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)
Description
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).
Time Frame
Baseline, Week 9
Title
Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)
Description
The BRIEF is a 86-item questionary evaluating executive functions rated on a 3-point Likert scale: 1 (never), 2 (sometimes) and 3 (often).
Time Frame
Baseline, Week 9
Title
Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children
Description
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.
Time Frame
Baseline, Week 9

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Université de Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5H3
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Metformin in Children and Adults With Fragile X Syndrome

We'll reach out to this number within 24 hrs