Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Metformin in Children and Adults With Fragile X Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Fragile X Syndrome Drug: Metformin Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-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 : September 1, 2018
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : September 1, 2019


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 Name: Glucophage




Primary Outcome Measures :
  1. Incident of adverses events reported during the study [ Time Frame: 9 weeks ]
    Number and severity of adverse events related to metformin treatment

  2. 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).


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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).

  4. 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).

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   10 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722290


Contacts
Layout table for location contacts
Contact: Artuela Çaku, MD 819-346-1110 ext 71035 Artuela.s.caku@usherbrooke.ca

Locations
Layout table for location information
Canada, Quebec
Université de Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1H 5H3
Contact: Artuela Çaku, MD    819-346-1110 ext 71035    Artuela.s.çaku@usherbrooke.ca   
Sponsors and Collaborators
Université de Sherbrooke
FRAXA Research Foundation

Layout table for additonal information
Responsible Party: Çaku, Principal Investigator, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT03722290     History of Changes
Other Study ID Numbers: 2019-2797
First Posted: October 26, 2018    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Çaku, Université de Sherbrooke:
Metformin
Insulin signalisation
Additional relevant MeSH terms:
Layout table for MeSH terms
Fragile X Syndrome
Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs