Metformin in Patients With Fragile X

NCT ID: NCT04141163

Last Updated: 2019-10-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-29
• Study Completion Date: 2021-03-31

Brief Summary

The purpose of this trial is to investigate the use of metformin in the treatment of Fragile X syndrome (FXS) patients. Metformin is an FDA approved compound with an established safety profile and minimal side effects that specifically targets and normalizes multiple aspects of the pathophysiology in FXS. This is a randomized double-blind placebo-controlled 2-arm parallel group design study of the drug metformin and placebo in FXS subjects with a primary outcome measure of safety/tolerability and secondary outcome measures on cognition, attention, anxiety, sleep, and physiologic and biochemical biomarkers.

Detailed Description

This trial will be a randomized placebo controlled, double-blind, parallel group design study of treatment with metformin on the primary outcome of safety/tolerance with secondary outcome measurements of the effects on cognition (encompassing social and repetitive behavior), attention, anxiety, and physiological and biochemical biomarkers of patients with FXS. FXS represents a well-defined population of ASD in which to test a specific targeted treatment looking at a well-defined set of cognitive and bioassay measures.

Trial length is designed to have a chance at seeing if the medication can improve cognitive outcome measures. The study duration includes the screening period and a 24-week single-blind drug/placebo phase.

Conditions

Fragile X Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

Subjects randomized to metformin will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin, 1,1 dimethylbiguanide, or systematic (IUPAC) name N,N-dimethylimidodicarbonimidic diamide, is an oral anti-diabetic medicine approved in the US by the FDA in 1994. It is marketed alone under the names metformin (generic), Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, and Diaformin and in combination with other drugs under the names Actoplus Met, Metaglip, Glucovance, Janumet, Kombiglyze XR, and PrandiMet

Placebo

Subjects randomized to placebo will start at 500mg once a day for 7 days and increase as is tolerated to 500mg twice a day for 7 days, then to 1000mg in the morning and 500mg at dinner for 7 days and then to the target dose of 1,000mg twice a day.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

No therapeutic effect

Interventions

Metformin

Metformin, 1,1 dimethylbiguanide, or systematic (IUPAC) name N,N-dimethylimidodicarbonimidic diamide, is an oral anti-diabetic medicine approved in the US by the FDA in 1994. It is marketed alone under the names metformin (generic), Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, and Diaformin and in combination with other drugs under the names Actoplus Met, Metaglip, Glucovance, Janumet, Kombiglyze XR, and PrandiMet

Intervention Type: DRUG

Placebo oral tablet

No therapeutic effect

Intervention Type: DRUG

Other Intervention Names

glucophage

Eligibility Criteria

Inclusion Criteria

• Male between the ages of 16-50 years old at the time of consent
• Diagnosis of full mutation FXS.
• Stable on any psychoactive medication for at least 4 weeks before receiving study drug, including antidepressants, stimulants, antipsychotics, and mood stabilizers.
• Seizure free for at least the past 3 months.
• No major health issues or diseases expected to interfere with the study
• No history of diabetes
• Not currently taking metformin at the time of enrollment
• Average basal blood glucose HgbA1c < 7.0
• Study partner with frequent contact with patient willing to accompany patient to visits and complete caretaker/partner study forms
• No contraindication to metformin
• Willing to complete all baseline assessments and study procedures

Exclusion Criteria

• Has a medical condition that would make treatment unsafe such as diabetes, pancreatic disease, liver or kidney disease, a history of epilepsy or seizure disorder that is not controlled, as well as any other medical condition as determined by the study doctor.
• Has an eating disorder that has been clinically diagnosed, predisposing them to low BMI.
• Has received any investigational compound within 30 days prior to the first dose of study medication.
• Has received metformin in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress.
• Has uncontrolled, clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• Has a known hypersensitivity to any component of the formulation of metformin.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 6 months prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Currently taking any excluded medication, supplements, or food products, or has taken any in the 3 weeks preceding Visit 1. This includes carbonic anhydrase inhibitors and the medication topamax.
• Has evidence of current cardiovascular, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking metformin or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to uncontrolled seizure disorders, and cardiac arrhythmias.
• History of any surgical intervention known to impact absorption (e.g., bariatric surgery or bowel resection).
• Compromised renal function at screening as determined by creatinine levels >1.5mg/dL and/or creatinine clearance <45mL/min based on Cockcroft-Gault calculation.
• Liver dysfunction at screening as evidenced by alanine transaminase (ALT/SGPT) values > 2X upper limit of normal or aspartate transaminase (AST/SGOT) values > 3X upper limit of normal or total bilirubin > 2X upper limit of normal.
• Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1.
• Has a history of abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator.
• Has abnormal Screening or Day 1 vital sign values that suggest a clinically significant underlying disease.
• Is at risk of suicide, has made a suicide attempt within the last year or has current active suicidal ideation. In accordance with previous FDA regulated studies on patients with FXS this determination will include asking 3 questions. 1) Has the subject made a suicide attempt? 2) Has the subject expressed any (active) suicidal thoughts or intent to harm him/herself or others? 3) Has there been a significant increase in the severity or frequency of self-injurious behaviors, or harm toward others, such that continued safety is a concern?
• Laboratory abnormalities in B12, or other common lab parameters that might contribute to cognition or participation in study
• In the opinion of the investigator or sponsor, the participant is unsuitable for inclusion in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

FRAXA Research Foundation

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Rowan University

OTHER

Sponsor Role: lead

Responsible Party

Sean McBride, M.D., Ph.D.

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sean McBride, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rowan University

Locations

Rowan University School of Osteopathic Medicine

Stratford, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Lauren Fedor

Role: CONTACT

Phone: 856-566-6003

Email: fedor@rowan.edu

Facility Contacts

Lauren Fedor

Role: primary

Other Identifiers

Pro2018000310

Identifier Type: -

Identifier Source: org_study_id