What side effects are associated with this type of intervention?

Common treatments for ALS, such as riluzole and edaravone, have known side effects. Riluzole can cause nausea, reduced lung function, and liver enzyme abnormalities. Edaravone may lead to bruising, gait disturbances, and allergic reactions. Metformin, being studied for ALS, is generally well-tolerated but can cause gastrointestinal issues like diarrhea and nausea, and in rare cases, lactic acidosis. Other investigational treatments, such as masitinib, may cause gastrointestinal symptoms, rash, and edema. It is important to discuss these potential side effects with a healthcare provider to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Amyotrophic Lateral Sclerosis (ALS). Riluzole, an antiglutaminergic drug, was the first to be approved and works by inhibiting glutamate release, which is thought to slow disease progression. Edaravone, another approved drug, acts as a free radical scavenger and has been shown to slow functional decline in ALS patients. While Metformin is being studied for its potential to reduce RAN proteins associated with the C9orf72 repeat expansion mutation in ALS, there are no current FDA-approved treatments specifically targeting this mechanism. The focus of existing treatments has primarily been on neuroprotection and reducing oxidative stress.

What other types of research exist?

Promising alternatives to Metformin for ALS patients in 2024 include riluzole, which improves survival, and investigational drugs targeting glutamate excitotoxicity and TDP-43 proteinopathies. Additionally, patisiran, vutrisiran, and inotersen, which target amyloid-related mechanisms, may offer novel therapeutic approaches.

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Biguanide

Metformin for ALS

Phase 2

Waitlist Available

Led By Laura Ranum, PhD

Research Sponsored by University of Florida

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects have a likely diagnosis of C9orf72 positive ALS/FTD

Subjects have a diagnosis of probable or definite ALS in accordance with the Revisited El-Escorial Criteria

Must not have

Subjects who are unwilling to sign informed consent or subjects who for any other reason in the judgment of investigator are unable to complete the study

Subjects with known history or presence of moderate or severe renal impairment as defined by an estimated glomerular filtration rate (eGFR) value below 30 mL/min/1.73 m2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through week 52

Awards & highlights

Approved for 20 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of Metformin may include digestive issues like nausea and diarrhea, low blood sugar levels especially when combined with other diabetes medications, vitamin B12 deficiency over long-term use which could cause anemia or nerve problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I likely have ALS/FTD linked to the C9orf72 gene.

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I have been diagnosed with ALS according to specific criteria.

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I can eat and drink normally without any assistance.

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I am not allergic to barium sulfate or Metformin.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am willing and able to sign the informed consent.

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My kidney function is significantly reduced, with an eGFR below 30.

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My liver is not functioning properly, shown by high enzyme levels or bilirubin.

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I am not pregnant, trying to conceive, or breastfeeding.

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My lab tests show I don't have the C9ORF72 gene mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in RAN protein levels

Number of subjects with treatment-emergent adverse events [Safety and Tolerability]

Secondary study objectives

Change in ALS Functional Rating Scale (ALSFRS-R) score

Side effects data

From 2015 Phase 4 trial • 156 Patients • NCT02002221

13%

Nasopharyngitis

10%

Hyperhidrosis

Hunger

Tremor

Asthenia

Hypoglycaemia

Femoral neck fracture

Squamous cell carcinoma of the tongue

100%

80%

60%

40%

20%

Study treatment Arm

Vildagliptin (LAF237)

Placebo

Awards & Highlights

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: C9orf72 positive ALSExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Metformin

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Amyotrophic Lateral Sclerosis (ALS) include riluzole, edaravone, and sodium phenylbutyrate-taurursodiol (PB-TURSO). Riluzole works by inhibiting glutamate release, which helps reduce excitotoxicity that can damage motor neurons. Edaravone is an antioxidant that reduces oxidative stress, thereby protecting neurons from damage. PB-TURSO combines two drugs that reduce neuronal cell death, potentially slowing disease progression. Metformin, currently under investigation for C9orf72 ALS, aims to reduce toxic dipeptide repeat proteins produced by the C9orf72 repeat expansion mutation. These treatments are crucial as they target different pathways involved in ALS progression, offering hope for slowing the disease and improving patient outcomes.

Development of LNA Gapmer Oligonucleotide-Based Therapy for ALS/FTD Caused by the C9orf72 Repeat Expansion.The Emerging Role of DNA Damage in the Pathogenesis of the C9orf72 Repeat Expansion in Amyotrophic Lateral Sclerosis.