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Metformin in Children and Adults With Fragile X Syndrome

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ClinicalTrials.gov Identifier: NCT03722290
Recruitment Status : Recruiting
First Posted : October 26, 2018
Last Update Posted : October 26, 2018
Sponsor:
Collaborator:
FRAXA Research Foundation
Information provided by (Responsible Party):
Çaku, Université de Sherbrooke

Tracking Information
First Submitted Date  ICMJE October 24, 2018
First Posted Date  ICMJE October 26, 2018
Last Update Posted Date October 26, 2018
Actual Study Start Date  ICMJE September 1, 2018
Estimated Primary Completion Date June 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
  • Incident of adverses events reported during the study [ Time Frame: 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 [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
  • Level of cortical excitability using Transcranial Magnetic Stimulation (TMS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metformin in Children and Adults With Fragile X Syndrome
Official Title  ICMJE Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
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 rafampicin complex 1) signaling 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fragile X Syndrome
Intervention  ICMJE 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 Name: Glucophage
Study Arms  ICMJE Experimental: Metformin
Metformin 500mg twice a day per os for 9 weeks
Intervention: Drug: Metformin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2019
Estimated Primary Completion Date June 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged between 10 et 40 years old
  • BMI > 18.3
  • Molecular diagnosis of FXS
  • Accompanied by his legal tutor
  • IQ < 70

Exclusion Criteria:

  • Pregnancy/Breastfeeding
  • Intolerance to metformin
  • History of lactic acidosis
  • Gastric/renal/hepatic pathology
  • Acute medical condition
  • Concomitant use of ACE inhibitors
  • Taking more than 3 antipsychotic drugs
  • Modification of antipsychotic treatments in the last 6 weeks
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Artuela Çaku, MD 819-346-1110 ext 71035 Artuela.s.caku@usherbrooke.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03722290
Other Study ID Numbers  ICMJE 2019-2797
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Çaku, Université de Sherbrooke
Study Sponsor  ICMJE Université de Sherbrooke
Collaborators  ICMJE FRAXA Research Foundation
Investigators  ICMJE Not Provided
PRS Account Université de Sherbrooke
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP