A Trial of Metformin in Individuals With Fragile X Syndrome (Met)

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT03862950
• Date of registration: 26/02/2019
• Prospective Registration: Yes
• Primary sponsor: University of Alberta
• Public title: A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
• Scientific title: A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS)
• Date of first enrolment: May 24, 2019
• Target sample size: 120
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03862950
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Canada

Contacts

• Name: Research Coordinator

• Name: Francois Bolduc, MD
• Affiliation: University of Alberta

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject has Fragile X syndrome with a molecular genetic confirmation of the full FMR1
mutation (>200 CGG repeats) or the other loss of function mutations of the FMR1 gene
(SNVs and deletions of the gene).

- Subject is a male or non-pregnant, non-lactating female age 6 through 35 years,
inclusive.

- Subjects who are capable of becoming pregnant must use an acceptable method of birth
control for the duration of the study. Acceptable forms of birth control include
abstinence (only for subjects who are not sexually active), intrauterine devices in
place for at least 3 months, oral contraceptives, surgical sterilization, or adequate
barrier methods.

- Subject must have a caregiver (parent, guardian, or other legally authorized
representative) who is willing to participate in the whole study.

- Subject and caregiver are able to attend the clinic regularly and reliably.

- Subject and/or subject's caregiver is able to understand, read, write and speak
English or French fluently to complete study-related materials.

- For subjects who are not their own legal guardian, subject's caregiver is able to
understand and sign an informed consent to participate in the study.

- The use of concomitant medication must be stable, in terms of dose and dosing regimen,
for at least 4 weeks prior to Screening and must remain stable during the period
between first visit (Screening) and the commencement of the study; every effort should
be made to maintain stable regimens of allowed concomitant medications from the time
of commencement of double-blind study medication until the last study assessment.

- Behavioral/educational treatments must be stable for 4 weeks prior to first visit
(Screening) and must remain stable during the period between Screening and the
commencement of randomized double-blind study medication.

- 10. Overall age equivalent is not higher than 13 and IQ is not higher than 85, as
assessed at Screening on the Leiter-III, and subject must speak at least occasional
3-word phrases.

Exclusion Criteria:

- Families that are not cooperative and will not follow through with the demands of this
study.

- Subject has a life-threatening medical problem or other major systemic illness that
compromises health or safety and/or would interfere with this study.

- Age younger than 6 or older than 35 years.

- History of intolerable adverse events with metformin.

- Current or recent metformin treatment (within the past 4-months).

- BMI inferior to 2 standard deviations below the mean for age using the World Health
Organization scale.

- Serum creatinine > 1.4 mg/dl (female) or > 1.5 mg/dl (male).

- History of metabolic acidosis or a condition with lactic acidosis.

- Severe Vitamin B12 deficiency.

- Pregnancy at screening or unwillingness to use acceptable method of birth control, if
applicable.

- Age equivalent higher than 13 or IQ higher than 85 on the Leiter-III at Screening.



Age minimum: 6 Years
Age maximum: 35 Years
Gender: All

Health Condition(s) or Problem(s) studied

Mental Retardation, X-Linked

Trinucleotide Repeat Expansion

Neurobehavioral Manifestations

Fragile X Mental Retardation Syndrome

Fra(X) Syndrome

Fragile X Syndrome

Intellectual Disability

FXS

Sex Chromosome Disorders

Genetic Diseases, X-Linked

Intervention(s)

Drug: Metformin

Drug: Placebo Medication

Primary Outcome(s)

Change from baseline in the Expressive Language Sampling (ELS) mean Number of Different Words (NDW) score [Time Frame: Baseline, End of Treatment/Week 16]

Secondary Outcome(s)

Change from baseline in the FXS-normed Aberrant Behavior Checklist - Community Edition (ABC-C) [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the Care Related Quality of Life (CarerQoL) overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Oral Reading Recognition Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Picture Vocabulary Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the Vineland Adaptive Behavior Scales-Third Edition (VABS-III) Adaptive Behavior Composite Score [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the Pediatric Quality of Life Questionnaire (PedsQL) Parent Proxy overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in Eye Tracking [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the Anxiety Depression and Mood Screen (ADAMS) overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox List Sorting Working Memory Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in Event Related Potentials during the Auditory Oddball Paradigm and Pseudoword Paradigm [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Dimensional Change Card Sort Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Pattern Comparison Processing Speed Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Speeded Matching Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the Child Sleep Habits Questionnaire (CSHQ) overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the Sensory Profile-2 or Sensory Profile Adolescents/Adults [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Improvement of symptoms in FXS using the Clinical Impression - Improvement (CGI-I) scale [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the Swanson, Nolan and Pelham Questionnaire (SNAP-IV) overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in the EuroQol-5D (EQ-5D) overall score [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Change from baseline in The Memory Game [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Flanker Inhibitory Control and Attention Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the NIH Toolbox Picture Sequence Memory Test [Time Frame: Baseline, End of Treatment/Week 16]

Change from baseline in the Visual Analog Scale (VAS) [Time Frame: Baseline, Week 8, End of Treatment/Week 16]

Secondary ID(s)

FXSMET-2018 Version 14

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

St. Justine's Hospital