Antioxidants for ALS

(MICABO-ALS Trial)

Overseen By Rehana Hussain, M.Sc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dallas VA Medical Center

Disqualifiers: Other neurodegenerative diseases, Unstable illness, HIV, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if antioxidants, such as vitamin E, can slow or halt the progression of amyotrophic lateral sclerosis (ALS). ALS is a serious condition affecting nerve cells in the brain and spinal cord, leading to muscle weakness. The trial builds on earlier research suggesting that antioxidants might combat oxidative stress, believed to be a major cause of ALS. Individuals with a confirmed ALS diagnosis may be suitable for this trial, especially if they are on a stable dose of the ALS medication riluzole. Participants will take specific doses of safe, over-the-counter antioxidants. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important ALS advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking riluzole for ALS, you must be on a stable dose for at least thirty days before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that antioxidants are generally safe for people. Studies suggest that Vitamin E, one of the antioxidants in this trial, is well-tolerated and might even help lower the risk of developing ALS. The FDA has approved N-acetyl cysteine (NAC), another antioxidant in this study, for other uses, indicating a good safety record. Derived from an amino acid, NAC is considered safe for most people.

Previous research indicates that supplements containing cysteine, which can increase glutathione (a natural antioxidant in the body), seem to be safe. No strong evidence suggests harmful effects from these antioxidants. Based on these findings, the antioxidants tested in the trial are likely to be well-tolerated and safe for people with ALS. ^{1 2 3 4 5}

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

Researchers are excited about using antioxidants for ALS because they offer a different approach compared to traditional treatments like Riluzole and Edaravone, which mainly work by slowing disease progression. Antioxidants like vitamin E, N-Acetylcysteine, and Taurursodiol aim to reduce oxidative stress, a key factor in ALS progression, potentially providing a complementary effect to existing therapies. This treatment uses widely accessible, over-the-counter ingredients, which could make it easier for patients to access and incorporate into their daily routines.

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

Research has shown that antioxidants might help treat amyotrophic lateral sclerosis (ALS). One study found that vitamin E slowed ALS progression. In this trial, participants will receive antioxidants such as vitamin E, NAc cysteine, L-cystine, nicotinamide, and taurursodiol, which can reduce oxidative stress, believed to play a role in ALS. Another study suggested that consuming foods rich in carotenoids, which are antioxidants, may delay the onset of ALS. These findings suggest that antioxidants could offer a promising, low-cost, and low-risk option for managing ALS symptoms. ^{2 6 7 8 9}

Who Is on the Research Team?

Olaf Stuve, M.D., Ph.D.

Principal Investigator

Dallas VA Medical Center

Are You a Good Fit for This Trial?

The MICABO-ALS trial is for adults aged 21 to 80 with a clinical diagnosis of ALS, who have been on a stable dose of riluzole for at least 30 days. Participants must be able to consent and comply with the study procedures. Those with unstable illnesses, other neurodegenerative diseases, HIV, or recent drug abuse are excluded.

Inclusion Criteria

Patients taking riluzole for ALS must be on a stable dose for at least thirty days prior to the baseline visit

Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB)

A doctor has diagnosed you with ALS based on specific criteria.

Exclusion Criteria

Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc.) over the last 30 days

Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures

You have been diagnosed with other brain diseases like Parkinson's or Alzheimer's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose anti-oxidants for ALS treatment

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antioxidants

Trial Overview This trial tests high doses of antioxidants not previously used in an earlier EH301 trial to slow or stop ALS progression. The focus is on combating oxidative stress believed to cause ALS. If successful, this could lead to an accessible treatment option.

How Is the Trial Designed?

Group I: Antioxidants Experimental Treatment 1 Intervention

Eligible patients will receive over-the-counter anti-oxidants, namely vitamin E, NAc cysteine, L-cystine, Nicotinamide and Taurursodiol at defined doses.

Antioxidants is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

Approved in European Union as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

Approved in Canada as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

Who Is Running the Clinical Trial?

Dallas VA Medical Center

Lead Sponsor

Trials

35

Recruited

4,800+

Published Research Related to This Trial

In a study involving 20 ALS patients, edaravone treatment (60 mg) significantly reduced the decline in motor function, as measured by the ALS functional rating scale, compared to the six months prior to treatment.

Edaravone also effectively lowered levels of 3-nitrotyrosine in cerebrospinal fluid, indicating a reduction in oxidative stress, which is believed to contribute to ALS progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study). Yoshino, H., Kimura, A.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7016185/

Antioxidant Alternatives in the Treatment of Amyotrophic ... Vitamin E was associated with a slower progression of ALS (Orrell et al., 2004) and in one study it was observed that regular use of vitamin E supplements was ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04244630

Mitochondrial Capacity Boost in ALS (MICABO-ALS) Trial Eligible patients will receive over-the-counter anti-oxidants, namely vitamin E, NAc cysteine, L-cystine, Nicotinamide and Taurursodiol at defined doses.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8394119/

NAD+ Precursors and Antioxidants for the Treatment of ... Thus, the authors of this study suggest that the consumption of foods high in carotenoids may help to prevent or delay the onset of ALS, though ...

4. degruyterbrill.com degruyterbrill.com/document/doi/10.1515/biol-2022-0842/html?lang=en&srsltid=AfmBOooKirU1CdC_38mIOHthQBeixub_xzxoGST4ikR--V2qYyHQt_qy

Exploring antioxidant strategies in the pathogenesis of ALS It has been suggested that antioxidants could serve as a potential therapy for ALS, given their ability to alleviate oxidative stress, a factor ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/0022510X96000718

Survival in patients with amyotrophic lateral sclerosis ... Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (Als) by an array of antioxidants and added other drugs to the ...

6. withpower.com withpower.com/trial/phase-3-amyotrophic-lateral-sclerosis-9-2020-f5285

Antioxidants for ALS (MICABO-ALS Trial) Research suggests that Vitamin E, an antioxidant, is generally safe for human use. Studies have shown that it may help reduce the risk of ALS and is well- ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac/

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More N-acetyl cysteine (NAC) comes from the amino acid L-cysteine. Amino acids are building blocks of proteins. NAC has many uses and is an FDA approved drug.

8. degruyterbrill.com degruyterbrill.com/document/doi/10.1515/biol-2022-0842/html?lang=en&srsltid=AfmBOorfA2NjenW7FUWoHiRY8ANhszRtgv8Y1ECyeuYb-qz8Qaox5lFH

Exploring antioxidant strategies in the pathogenesis of ALS It has been suggested that antioxidants could serve as a potential therapy for ALS, given their ability to alleviate oxidative stress, a factor ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/21678421.2019.1697029

Full article: ALSUntangled No. 52: Glutathione As an ALS treatment, glutathione and cysteine-containing supplements that increase glutathione appear reasonably safe, and they have a plausible ...