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
About this trial
This is an interventional treatment trial for Fragile X Syndrome focused on measuring Metformin, Insulin signalisation
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
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
NCT ID
NCT03722290
First Posted
October 24, 2018
Last Updated
February 1, 2021
Sponsor
Université de Sherbrooke
Collaborators
FRAXA Research Foundation
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
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Metformin in Children and Adults With Fragile X Syndrome
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