NCT04220021

Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD

A Single-Center, Open Label Study to Assess the Safety and Tolerability of Metformin in Subjects With C9orf72 Amyotrophic Lateral Sclerosis Over 24 Weeks of Treatment

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The primary objective is to assess the safety and tolerability of Metformin in subjects with C9orf72 amyotrophic lateral sclerosis administered for 24 weeks. The overall objective is to determine if Metformin is safe in C9orf72 ALS patients and is a potentially viable therapeutic treatment for C9-ALS that reduces repeat-associated non-canonical start codon - in DNA (non-ATG) (RAN) proteins that are produced by the C9orf72 repeat expansion mutation.

Detailed description

The C9orf72 repeat expansion is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Metformin, a well-tolerated diabetes drug, blocks a key pathway for expression of toxic proteins produced from the C9orf72 repeat expansion via repeat associated non-canonical start codon - in RNA (non-AUG) (RAN) translation. In mouse model of C9-ALS/FTD, metformin treatment decreases RAN protein levels and improves disease features. This current study is a small-scale clinical trial to assess the safety and potential efficacy of metformin for the treatment of C9-ALS/FTD.

Conditions

• C9orf72 Amyotrophic Lateral Sclerosis (ALS)
• Frontotemporal Dementia

Interventions

Type	Name	Description
DRUG	Metformin	Metformin is a widely used, well-tolerated drug that has been used for decades as a first-line defense for treating type 2 diabetes. Its safety has been well established. Subjects will begin treatment with Metformin at a dosage of 500mg with an escalation of dosage by 500mg every week to a maximal dosage of 2000mg. Dosing will be twice daily.

Timeline

• Start date: 2020-01-10
• Primary completion: 2024-08-26
• Completion: 2026-06-30
• First posted: 2020-01-07
• Last updated: 2025-12-02
• Results posted: 2025-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study