Metformin in Patients With Fragile X

NCT04141163 | Unknown Phase 1 FDA Drug

• 1 other identifier: Pro2018000310
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (1)

• The safety and tolerability of metformin in patients with Fragile X Syndrome as assessed by the number of adverse events reported during the course of the study.

  measured by the number of reported adverse events, assessed using the Safety Monitoring Uniform Report Form (SMURF), modified for metformin use

  1-2 years

Secondary Outcomes (1)

• Patients taking Metforming have improved cognition, sleep, attention or anxiety from baseline to the end of the study

  1-2 years

Study Arms (2)

Metformin

EXPERIMENTAL

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.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo oral tablet

Interventions

Metformin 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

Also known as: glucophage

Metformin

Placebo oral tablet DRUG

No therapeutic effect

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rowan University: lead
• FRAXA Research Foundation: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

Rowan University School of Osteopathic Medicine

Stratford, New Jersey, 08084, United States

RECRUITING

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Sean McBride, MD, PhD

  Rowan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauren Fedor

CONTACT

856-566-6003; fedor@rowan.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 28, 2019
• Study Start: October 29, 2019
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: October 31, 2019

Record last verified: 2019-10

Locations

US (1)