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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Metformin is safe and effective for treating a specific type of ALS linked to the C9orf72 gene mutation. Researchers aim to determine if Metformin can reduce certain proteins in the body that may be harmful in this type of ALS. Suitable candidates for the trial have been diagnosed with ALS caused by the C9orf72 gene change and can eat and take pills normally. Participants will take Metformin for about six months to assess its efficacy and safety. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Metformin is likely to be safe for humans with C9orf72 ALS?

Research has shown that metformin, a common diabetes drug, might be safe for people with ALS, a disease affecting the nervous system. Some studies suggest that metformin could lower the risk of developing ALS, indicating it might be well-tolerated. However, in certain animal studies, metformin produced harmful effects, but these results do not always apply to humans.

This trial is in an early stage, so researchers are carefully monitoring for any side effects. While some uncertainty remains about metformin's safety for ALS, its long-standing use for diabetes might offer some reassurance. It's important to remember that reactions can vary, and ensuring safety for ALS patients is the main goal of this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Researchers are excited about using Metformin for ALS because it offers a new approach to treating this challenging condition. Unlike traditional ALS treatments, which mainly focus on managing symptoms, Metformin targets cellular energy processes, potentially slowing disease progression. This is particularly promising for patients with C9orf72 positive ALS, as Metformin's mechanism of action may address underlying genetic factors. The possibility of repurposing a well-known diabetes medication like Metformin for ALS also brings hope for a faster transition from trials to clinical use, given its established safety profile.

What evidence suggests that Metformin might be an effective treatment for ALS?

Research suggests that Metformin might help people with ALS, especially those with the C9orf72 mutation. In this trial, participants with C9orf72 positive ALS will receive Metformin. Studies have shown that Metformin reduced harmful protein levels in cells and mice with C9-ALS and improved their symptoms. Another study found that Metformin use is linked to a lower risk of developing ALS. However, some research indicates Metformin might not benefit all ALS patients and could be harmful, particularly for women. While there is hope, the results are mixed, and more research is needed. ^{1 2 6 7 8}

Who Is on the Research Team?

Laura Ranum, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142699/

Insulin and Metformin are Associated With Reduced Risk of ... Metformin use is associated with a significantly reduced risk of ALS (PRR 0.567).

2. cdmrp.health.mil cdmrp.health.mil/alsrp/research_highlights/23Plowman_Ranum_Wymer_highlight.aspx

The Therapeutic Potential of Metformin in ALS The team also showed that Metformin treatment reduced protein levels in cells and a mouse model of C9-ALS and improved behavior and disease ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04220021

Study Details | NCT04220021 | Safety and Therapeutic ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11726913/

Genetic Variation in Targets of Antidiabetic Drugs and ... Several experiments have explored the effects of antidiabetic drugs on ALS. Metformin has been observed to delay disease progression in a ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0024189

Metformin Treatment Has No Beneficial Effect in a Dose ... This study suggests that metformin is a poor candidate for clinical trial in ALS patients and that the possibility of harmful effects of metformin in female ALS ...

6. neals.org neals.org/als-trials/nct04220021

A Single-Center, Open Label Study to Assess the Safety ... 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.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10957794/

Antidiabetics, statins and the risk of amyotrophic lateral sclerosis Harmful effects of the antidiabetic metformin on the course of ALS have been suggested in SOD1G93A mice [12]. Deleterious effects of statins on motor neurons ...

8. mednexus.org mednexus.org/doi/abs/10.1002/cdt3.141

Insulin and Metformin are Associated With Reduced Risk of ... In MedWatch, Insulin use is associated with a significantly reduced risk of amyotrophic lateral sclerosis (ALS) (Proportional Reporting Ratio 0.401). Metformin ...