What is a double-blind, randomized, placebo-controlled trial?
This means that the participant/family and the study staff do not know which treatment is being given to each participant. This is the gold standard in research as it allows the researchers to avoid bias when looking at how participants are responding in the study. In this trial, participants will either be given metformin or a placebo (this will be identical to the metformin, but will not contain any active drug). This means that the placebo is a “control”. So, because no one knows if each participant is on metformin or placebo (until the whole study is over), the researchers will have to judge if participants are responding to treatment or not without knowing if they are taking active drug. The researchers will not be swayed into thinking a participant is doing better while on metformin because they won’t know if the participant actually is on metformin! This trial is also randomized because each participant is randomly assigned to one of the two options.
What is a placebo?
A placebo is a substance or treatment which is designed to have no therapeutic value. In this trial, the participant will receive either metformin or a placebo. The placebo will be identical to the metformin and you and the study staff will not know which treatment you are receiving until the whole study is over.
What is an open label trial?
This means that both the researchers and participants know which treatment is being administered. In our case, after the 4 month double-blind part (see above for definition) of the trial is over, you may join the open label part where you will know you are receiving metformin for 2 years. This is one of the benefits of joining this study! Anyone who completed the double-blind part of the study will be eligible to join the open-label portion.
Will I know if my child is on metformin?
There are two parts to this study. During the first part (which lasts 4 months), you will not know if your child is on metformin until the entire study is over and closed. This is the double-blind, randomized, placebo-controlled part (see above for definition). During the second part (which lasts 2 years), if you choose to join, the participant will receive metformin. There is no placebo for this part. This is called an open label trial (see above for definition).
You are free to change your mind about participating at any time, for any reason. If you do stop participating early, we will ask you to come back to the UofA for one final visit so that we can run safety tests and collect any final data. Information gathered about a participant who has terminated the study early will be kept for analysis unless the participant/participant’s caregivers specifically ask for this information to be removed from the analysis. Any unused biological samples will be destroyed.
What are the benefits of taking part in the study?
Participants with FXS:
may experience an improvement in physical health, behavioral symptoms, and/or cognitive abilities as a result of treatment with metformin.
will undergo neuropsychological assessments, the results of which may be made available to the family of participants on request.
will receive medical exams offered through the study. Additionally, a complete blood count will be conducted as a part of this study. Participants/caregivers will be informed of clinically significant findings from either the medical exam or CBC as appropriate.
may understand that they are contributing to the scientific knowledge that may lead to expansion of the targeted treatment options for subjects with FXS.
will have direct access to health professionals and will be followed very closely during the study.
You will also be eligible to participate in the 2 year open label portion of the trial (see above for definition) during which the participant will receive metformin (as opposed to the first part of the trial where the participant could be on metformin or a placebo (see above for definition).
Dr. Bolduc will:
help you find resources in your location
connect you with other health professionals if needed
connect you to our Fragile X Clinic
How will I know if I was accepted in the study?
We will start by scheduling a call with you and our Research Coordinator. During this call, she will ask you some questions to see if you/your child is eligible for the study. Upon completion of the questions (should take 15-30 minutes), she will let you know if you are eligible for the first visit. At that visit, a couple more criteria will need to be looked at before you will be enrolled into the study. For example, IQ will be measured first and the inclusion/exclusion criteria for that will need to be met before enrollment can take place. Language testing will also be completed and we will ensure the participant can meet the requirement of being able to speak 3 word sentences. If all criteria are met, the participant will be enrolled and the rest of the study tasks for visit 1 will be completed and the study drug will be administered to you.
What is the overall timeline of the study?
Participation in the double-blind part of the study (see above for definition) will last 4 months. During this time, the participant will be taking either metformin or a placebo (an identical capsule that contains no active drug). Upon completion of this, participants have the option of then enrolling in the open label portion of the trial (see above for definition), which is a 2 year addition to the study during which all participants will receive metformin and be followed by Dr. Bolduc with two more visits to the UofA. Anyone who completed the 4 month double-blind portion of the trial is eligible for the 2 year open label portion.
How much time will this take?
Participation in the double-blind portion (see above for definition) will be 4 months. During this time, you will have 3 visits to the UofA. The first visit is done over two days. The second visit will only be about half a day, and the third visit will again be done over two days, but there are fewer tasks to complete and should be shorter than visit 1. During the rest of the time, we will ask you to keep track of the study medication (you will log every day when it is taken) as well as any side effects and any other medications that are taken (e.g. Tylenol). There will also be phone calls from the study staff to assess for these things at weeks 1, 2, 3, 4, and 12. These calls should only take 5-10 minutes. If you choose to join the open label portion afterwards (see above for definition), participation will last 2 years. There will be two more two-day visits to the UofA during this time and we will ask you to keep track of the same things as before. There will also be short phone calls during this time at weeks 1, 2, 3, 4, 20, 36, 52, 68, 84, and 100.
Are all levels of cognitive ability accepted?
There are eligibility criteria related to cognitive ability:
Overall age equivalent is not higher than 13
IQ is not higher than 85
Both of these are as assessed at your first visit using the Leiter-III which is administered by a psychologist.
The participant must also speak at least occasional 3-word sentences.
Do I need to be able to read to participate in the study?
The participant and/or participant’s caregiver must be able to understand, read, write and speak English fluently to complete study-related materials.
The participant or participant’s caregiver must also be able to understand and sign an informed consent to participate in the study.
Can an aide help me?
Every adult and child who participates in the study will need a caregiver (parent, guardian, or other legally authorized representative) who is willing to participate in the whole study and who will attend the clinic regularly and reliably with them.
An aide who is not a parent, guardian, or other legally authorized representative can attend appointments. Please discuss this with the Research Coordinator during the initial phone call.
What information do you need to take part in the study?
The Research Coordinator will discuss everything with you on the phone as a first step. She will be asking questions about you and your family in order to determine if you/your child are eligible for this study. We will need to know that the potential participant is between 6-35 years old, can speak in at least 3 word sentences, you are willing to travel to Edmonton 3 times in 4 months, and the participant can swallow mid-sized capsules daily. You can see the full list of inclusion and exclusion criteria here: http://metforminfxs.com/inclusionexclusion-criteria.html.
Additional questions will be asked, but you only need to answer what you feel comfortable with and you can stop any time. If you do participate, at your visit, we will collect medical history and demographic information, among other things.
Will I receive any payment to take part in the study?
You will not be paid to participate in this study, however all of your expenses will be covered/reimbursed. Flights and hotel will be booked by the Research Coordinator directly and paid for by the study. Other things that will be reimbursed, if applicable, include mileage and parking fees. Meals will be paid for by the study via a reloadable debit card that you will receive at your first visit.
How will my information be stored?
Your information will be put into a secure database managed by the University of Alberta. All paper copies will be stored in a locked filing cabinet in a locked room at the University of Alberta.
Who are the researchers?
Dr. Francois Bolduc is the Lead Principal Investigator for the Canadian sites and runs the trial at the university of Alberta in Edmonton. He is an associate professor of Pediatrics and medical genetics at the University of Alberta. He pioneered the study of memory in the fruit fly model of Fragile X syndrome (FXS) and was part of the team who discovered the role of metformin in memory improvement in FXS.
Dr. Sebastien Jacquemont and Dr. Sarah Lippe are the Principal Investigators for the trial at CHU Sainte-Justine in Montreal. Sébastien Jacquemont is a medical geneticist and associate professor at the University hospital of St. Justine. His strong interest in translational research has led him to develop and conduct, in collaboration with other investigators some of the first targeted clinical trials in patients with Fragile X syndrome. Dr. Sarah Lippé is full Professor of Neuropsychology at University of Montreal, Fellow of the Fond de Recherche du Québec en Santé (FRQS), Deputy Head of the research axis Brain and Child Development at CHU Sainte-Justine Research Center, and scientist at CHU Sainte-Justine. Sarah is currently leading EEG phenotyping of two international clinical trials. Her laboratory infrastructure includes EEG, eye tracking, physiological measures, in addition to MEG and MRI access.
Learn more about the Montreal team here: http://metforminfxs.com/chu-sainte-justine---english.html
Dr. Randi Hagerman is the Principal Investigator for the United States at the MIND Institute in Sacramento, California. Dr. Hagerman is a developmental and behavioral pediatrician and has studied patients with fragile X syndrome, autism, and other neurodevelopmental disorders.
You will need to be Canadian to participate in the trial. We have two sites: one site is in Edmonton, Alberta where we are accepting participants from British Columbia, Alberta, Saskatchewan, Manitoba, Yukon, North West Territories, and Nunavut and one site is in Montreal, Quebec, where we are accepting participants from Ontario, Quebec, Nova Scotia, New Brunswick, Newfoundland and Labrador, and Prince Edward Island.
Do I have to travel to participate?
Yes, you will have to travel to the study site 3 times during the 4 month double-blind portion of the trial (see above for definition) and then 2 more times if you choose to participate in the 2 year open label portion (see above for definition).
What is the parent's involvement?
Parents will need to attend all visits. During visits, they will be asked to complete questionnaires and assist with urine, stool, and blood collection, answer questions from the doctor about medical history and anything that arises during the physical exam, and provide information on any medications the participant is taking. Between visits, the parent is responsible for keeping track of the dosing schedule and ensuring the participant is taking the medication properly. They will also need to keep track of any side effects and any other medications the participant takes. They will also need to answer phone calls from study staff.
Can you be on other medications?
Yes, you just cannot have had recent metformin treatment (in the past 4 months) and the use of other medications must be stable, in terms of dose and dosing regimen, for at least 4 weeks prior to the first visit 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 medications throughout the study. We will keep track of any other medications the participant takes for the duration of the study.
What age do you need to be to participate?
Anyone age 6-35 who meet all of the inclusion and exclusion criteria (found here: http://metforminfxs.com/inclusionexclusion-criteria.html) can participate in the double-blind part of the study that lasts 4 months (see above for definition). Anyone who completes that part may participate in the 2 year open label part (see above for definition), even if you have turned 36 years old since starting the double-blind part.
Are blood draws required?
Blood draws are required at three time points during the double-blind part of the study (see above for definition) and then again during the open label portion (see above for definition) after 1 year and 2 years. This is so safety labs can be completed. Blood will also be collected to look at molecular biomarkers. We understand that blood work can be a challenge for many individuals. We have lovely helpers called Child Life Specialists who will be there to help make it go smoothly! Please talk to the Research Coordinator about this and we can plan for extra time for the blood work to make it as stress free as possible.
Do you need to travel to Edmonton?
Yes, you will need to travel to Edmonton to attend study visits. There are three visits as part of the 4 month double-blind portion of the trial (see above for definition) and two additional visits if you participate in the 2 year open label portion (see above for definition). You will have time to explore the city! Check out West Edmonton Mall, the Edmonton Valley Zoo, or maybe catch an Oilers game while you’re here! The Edmonton River Valley is also a must see. It is the largest urban park in Canada, with more than 160 kilometres of maintained pathways and 20 major parks!