About the Trial
General Information:
This project is a randomized, double-blind, placebo-controlled trial of Metformin. The project is a collaborative effort between 2 sites in Canada and 1 in the United States to conduct parallel research for this medication in the treatment of individuals with Fragile X Syndrome (FXS). Early research and clinical experience has found that Metformin (a Type 2 Diabetes medication) can lessen weight gain and normalize appetite, but may also have possible cognitive benefits in some patients. The purpose of this trial is to measure the safety and efficacy of Metformin for patients with FXS in the area of language/cognition, eating/weight gain and overall behaviour.
The study is running at 2 sites in Canada and 1 similar study ongoing in the United States:
This study is recruiting children and adults, aged 6-35 years old, with FXS. If you participate in this study, you can expect three visits to our clinic over four months (an initial visit, a two-month visit, and a four-month visit). All visits will include a medical check-up, blood, urine and stool collection, as well as several assessments of language, development, and behaviour. Study personnel will phone you regularly throughout the study to monitor potential side effects.
To learn more about this study in Canada, please contact:
Additional Study Information
Why Metformin?
Metformin has been shown to be effective and safe in decreasing weight gain associated with atypical anti-psychotic use and is well tolerated by children and adults with ASD aged 6-17 years old (Anagnostou et al., 2016 ). It has been utilized for treatment of obese children and adults who do not have Type 2 Diabetes with short-term reduction in Body Mass Index (BMI) (Park et al., 2009 & Klein et al. 2006 ).
Metformin has emerged as a candidate drug for the targeted treatment of Fragile X Syndrome (FXS) based on animal studies showing rescue in the FXS model (Monyak et al. 2016; Weisz et al. 2015 & Gantois et al. 2017 ). Dr. Randi Hagerman (UC Davis MIND Institute) and her team have used Metformin in the clinical treatment of over 20 individuals between the ages of 4 and 58 years of age with FXS and have found benefits not only in reducing weight-gain and normalizing appetite, but also saw improvement in language and behaviour with doses up to 1000mg per day (Dy et al. 2017 ). Dr. Hagerman's team has recently reported the details of the first 7 patients treated clinically for whom pre and post Aberrant Behaviour Checklist results were obtained, and documented improvement in weight, language and behaviour (Dyer et al. 2017 ). This medication has been well tolerated, even in the 4-year-old patient with FXS, and it is now time to carry out a controlled trial.
Considering these promising preliminary results and the established safety of Metformin in children, our location (University of Alberta) is starting the trial here in Edmonton. Another Canadian center will also be carrying out this trial (CHU Ste. Justine, Montreal, QC), as well as a US location (UC Davis MIND Institute, Sacramento, CA).
Known Side Effects of Metformin
Very Common (greater than or equal to 10% of patients taking Metformin): diarrhea, nausea/vomiting, flatulence, fatigue and abdominal or stomach discomfort.
Less Common (less than 10% of patient taking Metformin): stomach discomfort, decreased appetite, dizziness or light-headedness, fever or chills, feeling weak or tired, back or side pain, muscle pain or cramping, pain or discomfort, cold sweats, coma, confusion, difficult or laboured breathing, feeling of warmth, or a heartbeat/pulse that is fast, irregular, pounding or racing.
Rare (less than 1% of patients taking Metformin):
Objectives of the Study:
Study Timelines
This study plans to enroll 60 participants over a 3-year period at each of the three study sites. Approximately 20 patients per year with Fragile X Syndrome will be randomized at each site to receive either Metformin or a placebo for a 4-month period. During this time, subjects will attend three visits to the recruiting site: the screening/baseline, 2-month, and 4-month visits. In addition, routine phone calls will be made once per week during the first month of the study, and once at Week 12 (Month 3).
This project is a randomized, double-blind, placebo-controlled trial of Metformin. The project is a collaborative effort between 2 sites in Canada and 1 in the United States to conduct parallel research for this medication in the treatment of individuals with Fragile X Syndrome (FXS). Early research and clinical experience has found that Metformin (a Type 2 Diabetes medication) can lessen weight gain and normalize appetite, but may also have possible cognitive benefits in some patients. The purpose of this trial is to measure the safety and efficacy of Metformin for patients with FXS in the area of language/cognition, eating/weight gain and overall behaviour.
The study is running at 2 sites in Canada and 1 similar study ongoing in the United States:
- Fragile X Clinic at the University of Alberta/Stollery Children's Hospital in Edmonton, Alberta, Canada.
- CHU Ste. Justine in Montreal, Quebec, Canada.
- MIND Institute at the University of California Davis Medical Center in Sacramento, California, USA.
This study is recruiting children and adults, aged 6-35 years old, with FXS. If you participate in this study, you can expect three visits to our clinic over four months (an initial visit, a two-month visit, and a four-month visit). All visits will include a medical check-up, blood, urine and stool collection, as well as several assessments of language, development, and behaviour. Study personnel will phone you regularly throughout the study to monitor potential side effects.
To learn more about this study in Canada, please contact:
- Edmonton site (Dr. Francois Bolduc, Principal Investigator)
- Clinical Research Coordinator: Send an Email or call 780-492-9461
- Montreal site (Dr. Sébastien Jacquemont, Principal Investigator)
- Maryse Thibeault or Sophie Morin, Study Coordinators
Additional Study Information
Why Metformin?
Metformin has been shown to be effective and safe in decreasing weight gain associated with atypical anti-psychotic use and is well tolerated by children and adults with ASD aged 6-17 years old (Anagnostou et al., 2016 ). It has been utilized for treatment of obese children and adults who do not have Type 2 Diabetes with short-term reduction in Body Mass Index (BMI) (Park et al., 2009 & Klein et al. 2006 ).
Metformin has emerged as a candidate drug for the targeted treatment of Fragile X Syndrome (FXS) based on animal studies showing rescue in the FXS model (Monyak et al. 2016; Weisz et al. 2015 & Gantois et al. 2017 ). Dr. Randi Hagerman (UC Davis MIND Institute) and her team have used Metformin in the clinical treatment of over 20 individuals between the ages of 4 and 58 years of age with FXS and have found benefits not only in reducing weight-gain and normalizing appetite, but also saw improvement in language and behaviour with doses up to 1000mg per day (Dy et al. 2017 ). Dr. Hagerman's team has recently reported the details of the first 7 patients treated clinically for whom pre and post Aberrant Behaviour Checklist results were obtained, and documented improvement in weight, language and behaviour (Dyer et al. 2017 ). This medication has been well tolerated, even in the 4-year-old patient with FXS, and it is now time to carry out a controlled trial.
Considering these promising preliminary results and the established safety of Metformin in children, our location (University of Alberta) is starting the trial here in Edmonton. Another Canadian center will also be carrying out this trial (CHU Ste. Justine, Montreal, QC), as well as a US location (UC Davis MIND Institute, Sacramento, CA).
Known Side Effects of Metformin
Very Common (greater than or equal to 10% of patients taking Metformin): diarrhea, nausea/vomiting, flatulence, fatigue and abdominal or stomach discomfort.
Less Common (less than 10% of patient taking Metformin): stomach discomfort, decreased appetite, dizziness or light-headedness, fever or chills, feeling weak or tired, back or side pain, muscle pain or cramping, pain or discomfort, cold sweats, coma, confusion, difficult or laboured breathing, feeling of warmth, or a heartbeat/pulse that is fast, irregular, pounding or racing.
Rare (less than 1% of patients taking Metformin):
- Allergic reaction, with symptoms including: rash, throat or tongue swelling, shortness of breath, vomiting, light-headedness and low blood pressure.
- Lactic Acidosis (a medical condition with build-up of lactate in the body which resulted in low pH (acidity) in the bloodstream). This can be associated with disorientation, yellow skin, shallow and rapid breathing, rapid heart rate, muscle pain, body discomfort, weakness, fatigue, reduced appetite, diarrhea, nausea, vomiting, or headache.
- Hypoglycemia (low blood sugar), which can cause shakiness, dizziness, sweating, and hunger. low blood sugar is rare, but can be seen when using other medications such as sulfonylurea.
- Liver damage.
- Anemia (characterized by iron-poor blood, which impedes delivery of oxygen throughout the body). This can be associated with fatigue, rapid heartbeat, shortness of breath, headache, difficulty concentrating, dizziness, pale skin, leg cramps and insomnia.
Objectives of the Study:
- Assess safety and tolerability of Metformin in individuals with Fragile X Syndrome aged 6 to 25 who are treated over a 4-month period.
- Assess the benefit of Metformin in the treatment of language deficits, behaviour problems, and obesity/excessive appetite in individuals with Fragile X Syndrome over a 4-month period.
- Assess the utility of innovative outcome measures, including measures of brain processing.
- Assess the molecular biomarkers that may predict which patients could be likely to benefit from Metformin treatment.
Study Timelines
This study plans to enroll 60 participants over a 3-year period at each of the three study sites. Approximately 20 patients per year with Fragile X Syndrome will be randomized at each site to receive either Metformin or a placebo for a 4-month period. During this time, subjects will attend three visits to the recruiting site: the screening/baseline, 2-month, and 4-month visits. In addition, routine phone calls will be made once per week during the first month of the study, and once at Week 12 (Month 3).
This research has been funded by the Stollery Children's Hospital Foundation through the Women and Children's Health Research Institute (WCHRI), thanks to a generous gift from the Azrieli Foundation/La Fondation Azrieli.
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Additional Canadian partners include the University of Alberta/Stollery Children's Hospital and CHU Ste. Justine, Université de Montréal.
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