Metformin in Patients With Fragile X

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT04141163
• Date of registration: 24/10/2019
• Prospective Registration: Yes
• Primary sponsor: Rowan University
• Public title: Metformin in Patients With Fragile X
• Scientific title: A Parallel Group Design Randomized Double-Blind Trial of Metformin Treatment in Patients With Fragile X Syndrome on Safety and Effects on Cognition, Anxiety, Attention and Biomarkers
• Date of first enrolment: October 29, 2019
• Target sample size: 40
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04141163
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Sean McBride, MD, PhD
• Affiliation: Rowan University

• Name: Lauren Fedor

• Name: Lauren Fedor

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Fragile X Syndrome

Intervention(s)

Drug: Metformin

Drug: Placebo oral tablet

Primary Outcome(s)

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. [Time Frame: 1-2 years]

Secondary Outcome(s)

Patients taking Metforming have improved cognition, sleep, attention or anxiety from baseline to the end of the study [Time Frame: 1-2 years]

Secondary ID(s)

Pro2018000310

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

FRAXA Research Foundation

University of Pennsylvania