Metformin for ALS

Overseen By Deborah Morrison, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must be taking: Metformin

Must not be taking: Hepatotoxic drugs

Disqualifiers: Renal disease, Liver disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if Metformin, a diabetes drug, is safe and effective for patients with C9orf72 ALS. The drug aims to block harmful proteins linked to their genetic mutation. Metformin has been used to treat type 2 diabetes for more than 60 years and is currently being investigated for its potential anticancer effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using potentially liver-damaging drugs and those who have taken experimental drugs recently. It's best to discuss your specific medications with the trial team.

How does the drug Metformin differ from other treatments for ALS?

Metformin is unique in ALS treatment as it is primarily a diabetes medication that works by improving insulin sensitivity and reducing glucose production in the liver, unlike existing ALS treatments like riluzole and edaravone, which focus on slowing disease progression and managing symptoms. ^{1 2 3 4 5}

Research Team

Laura Ranum, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for individuals with C9orf72 positive ALS/FTD who can take oral food and medication, have no severe allergies to Metformin or barium sulfate, and no implanted electrical devices or metal in their body. Pregnant women, those trying to conceive, breastfeeding mothers, people with recent cancer (except skin), liver disease, renal impairment (eGFR below 30 mL/min/1.73 m2), or on hepatotoxic drugs are excluded.

Inclusion Criteria

I am a woman who can have children and will take a pregnancy test before my swallow study exams.

I am willing to sign the consent form and HIPAA authorization.

I understand what participating in this study involves.

Exclusion Criteria

I haven't taken any experimental drugs recently.

I am not taking any medications that can harm my liver.

Anything else that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Metformin with dose escalation schedule twice daily for 24 weeks

24 weeks

Visit 1, Day 2 for first dose under supervision

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Treatment Details

Interventions

• Metformin

Trial Overview The trial tests the safety and potential therapeutic effects of Metformin over a period of 24 weeks in patients with C9orf72 amyotrophic lateral sclerosis. It aims to see if Metformin can safely reduce harmful proteins produced by a specific genetic mutation in these patients.

Participant Groups

Group I: C9orf72 positive ALS Experimental Treatment 1 Intervention

Subjects with C9orf72 positive ALS will be instructed in the use of Metformin and receive the first dose of Metformin under supervision of the investigator during Visit 1, Day 2. Subjects will then continue on Metformin per the dose escalation schedule twice daily for 24 weeks.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

ALS Association

Collaborator

Trials

46

Recruited

17,500+

Findings from Research

Edaravone has shown efficacy in reducing the decline of motor function in early-stage ALS patients, particularly in clinical trials conducted in Asia, where results were consistent with those from Japan.

The drug was well-tolerated across various studies, indicating a favorable safety profile, but its effectiveness appears to vary by region, with limited clinical utility reported in Europe and a need for further research in the United States and Argentina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug. Ortiz, JF., Khan, SA., Salem, A., et al.[2023]

A multicenter study involving 324 ALS patients found that long-term intravenous edaravone therapy was feasible and generally well tolerated, with potential adverse effects occurring in 16% of patients, primarily infections and allergic reactions.

However, the study showed no significant difference in disease progression or survival outcomes between patients receiving edaravone and those on standard therapy alone, indicating that edaravone may not offer a meaningful clinical benefit in the long-term management of ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis. Witzel, S., Maier, A., Steinbach, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Glatiramer acetate has no impact on disease progression in ALS at 40 mg/day: a double- blind, randomized, multicentre, placebo-controlled trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Edaravone Administered Orally and Via Nasogastric Tube in Healthy Adults: A Comparative Bioavailability Phase 1 Study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis. [2023]