Fragile X SyndromePhase 2NCT03722290
Metformin in Children and Adults With Fragile X Syndrome
A Phase 2 study testing Metformin in people with Fragile X Syndrome, run by Université de Sherbrooke at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 10 to 45 years
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2018to 1 Nov 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Aged between 10 et 45 years old
- BMI > 18.3
- Molecular diagnosis of FXS
- Accompanied by his legal tutor
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
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.
- Conditions
- Fragile X Syndrome
- Being tested
- Metformin
- Keywords
- Metformin, Insulin signalisation
- Medical subject headings
- Fragile X Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Oral administration of metformin 250mg (twice a day) for the 1st week followed by metformin 500mg (twice a day) for the next 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin 500mg twice a day per os for 9 weeks Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverses events reported during the study
Number and severity of adverse events related to metformin treatment
Measured: 9 weeks
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).
Measured: Baseline, Week 9
Secondary outcomes (5)
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
Measured: Baseline, Week 9
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
Measured: Baseline, Week 9
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).
Measured: Baseline, Week 9
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).
Measured: Baseline, Week 9
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.
Measured: Baseline, Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2018
- Study start1 Sep 2018
- Primary completion24 Oct 2019
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label trial
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- FRAXA Research Foundation
- Responsible party
- Principal investigator, Çaku, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03722290
- Sponsor's protocol ID
- 2019-2797
- Status last verified
- Feb 2021
- First submitted
- 24 Oct 2018
- Last updated
- 4 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
- ClinicalTrials.gov ID
- NCT03722290
- Acronym / sponsor ID
- 2019-2797
- Conditions
- Fragile X Syndrome
- Keywords
- Metformin, Insulin signalisation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- FRAXA Research Foundation
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 24 Oct 2019 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 26 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label trial
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin 500mg twice a day per os for 9 weeks |
Who may qualify
- Ages
- 10 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Aged between 10 et 45 years old
- BMI > 18.3
- Molecular diagnosis of FXS
- Accompanied by his legal tutor
Key exclusion criteria (7 listed)
- Pregnancy/Breastfeeding
- Intolerance to metformin
- History of lactic acidosis
- Gastric/renal/hepatic pathology
- Acute medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageOral administration of metformin 250mg (twice a day) for the 1st week followed by metformin 500mg (twice a day) for the next 8 weeks. | Drug | Metformin |
Primary outcome
Incidence 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).
5 secondary outcomes
Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)
Time frame: Baseline, Week 9
Level of synaptic plasticity using Electroencephalography (EEG)
Time frame: Baseline, Week 9
Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)
Time frame: Baseline, Week 9
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
Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children
Time frame: Baseline, Week 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Individual participant dataSharing planned: No
Related trials for Fragile X Syndrome
Not yet recruitingPhase 2
Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
Aggressive Behavior in Fragile X Syndome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruiting
Single Session Support for Parents of Children With Neurodevelopmental Disabilities Struggling With Anxious Avoidance
Neurodevelopmental Disorders, Autism Spectrum Disorder (ASD)
RecruitingObservational study
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
Not yet recruitingPhase 2/3
A Study to Investigate the Effects and Safety of Codabakalner for the Treatment of FXS in Male Participants and Adult Participants With ADS
Fragile X Syndrome (FXS), Autism Spectrum Disorder (ASD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Fragile X Syndrome, run by Université de Sherbrooke at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverses events reported during the study (time frame: 9 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.