Probiotics for ALS

(PROBIOTIC Trial)

Recruiting at 1 trial location

Overseen By Alice Cornet, B. SC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Antibiotics, Probiotics, Edaravone, others

Disqualifiers: Respiratory support, Immunodeficiency, Pregnancy, others

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether probiotics can change the lipid profiles of people with ALS-FTDSD, a type of motor neuron disease. Participants will receive either a probiotic supplement (beneficial bacteria) or a placebo for 24 weeks. Eligible individuals must have an ALS diagnosis and have shown symptoms like weakness or speech problems within the last two years. Participants should not currently use respiratory support or take certain medications. The study also seeks healthy individuals as a control group and caregivers to provide additional information. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new insights and potential treatments for ALS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must have stable dosages of certain ALS medications like edaravone, riluzole, or ALBRIOZA™ before joining. If you're taking probiotics or antibiotics, you need a 4-week break from them before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that probiotics are usually easy for people to take. They often aid digestion and have been studied for potential benefits in various health issues. In other studies, participants taking probiotics reported only a few side effects, typically mild ones like gas or bloating, which often resolve on their own.

While research continues on how probiotics might help with conditions like ALS, current studies have not revealed major safety concerns. However, since the trial is still in an early stage, more information is needed to fully understand their safety for people with ALS.

Overall, based on current knowledge, probiotics appear to be a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using probiotics for ALS because they offer a new way to potentially help manage the disease. Unlike standard treatments that focus on slowing the progression of ALS by targeting nerve cells, probiotics aim to influence the gut microbiome, which may have indirect effects on inflammation and overall health. This approach is different because it might improve quality of life by addressing symptoms through gut health, which is a novel angle for ALS treatment.

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

Research has shown a possible link between gut health and ALS, a disease affecting the nervous system. Studies have found that people with ALS often experience an imbalance in their gut bacteria, potentially worsening their symptoms. In this trial, participants in the experimental group will receive a probiotic formulation to help balance these bacteria. Animal studies suggest that correcting this imbalance might slow the disease's progression. Although human data is not yet available, researchers hope that probiotics could help by improving gut health. ^{1 2 5 6}

Who Is on the Research Team?

Genevieve Matte, MDCM, FRCP

Principal Investigator

CRCHUM

Are You a Good Fit for This Trial?

Adults diagnosed with ALS, regardless of FTD symptoms, who meet specific criteria like a certain level of physical function and willingness to maintain dietary habits. They must not have used probiotics recently and agree to avoid them during the trial. Women of childbearing age need a negative pregnancy test and must use birth control.

Inclusion Criteria

You must use two forms of contraception at the same time to prevent pregnancy.

We are looking for people who are generally healthy and don't have any specific medical conditions.

My weakness or speech problems started less than 2 years ago.

Exclusion Criteria

I use a machine to help me breathe.

I have been taking edaravone for less than 2 months.

I have been on a stable dose of riluzole or ALBRIOZA™ for less than a month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a probiotic formulation or placebo for 24 weeks

24 weeks

5 visits (in-person), 4 visits (phone calls)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 follow-up call

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Probiotic

Trial Overview The study is testing whether taking a probiotic formulation changes lipid profiles in ALS-FTDSD patients compared to those taking a placebo. The hypothesis suggests that the probiotics group will show different results over time.

How Is the Trial Designed?

Group I: Experimental Group Experimental Treatment 1 Intervention

Participants in this group will be randomized to receive a probiotic formulation for 24 weeks.

Group II: Control Group Placebo Group 1 Intervention

Participants in this group will be randomized to receive a placebo for 24 weeks.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Lallemand Health Solutions

Industry Sponsor

Trials

44

Recruited

4,100+

Founded

1934

Headquarters

Mirabel, Canada

Known For

Microbiome therapies

Top Products

Lacidofil, ProbioKid, Probio'Stick, IBacilluS+

Published Research Related to This Trial

In a study using G93A transgenic mice, which model human ALS, treatment with butyrate improved gut health and extended lifespan, suggesting that gut microbiome dysfunction may contribute to ALS progression.

Butyrate treatment also reduced the aggregation of a mutated protein associated with ALS, indicating its potential as a therapeutic agent for restoring gut microbiome balance and alleviating disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis. Zhang, YG., Wu, S., Yi, J., et al.[2019]

In a study of 26 ALS patients, 65.4% showed signs of Glutamate Metabolism Dysfunction (GMD) after consuming a protein shake, indicating a potential issue with how their bodies process dietary glutamate compared to 30% of unaffected family members.

During a six-month treatment phase, patients with stable or improving GMD status experienced a slower decline in ALS symptoms, suggesting that addressing GMD could be a promising therapeutic target for ALS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theme 6 Tissue biomarkers. Garnaas, KR., Kittelsrud, J., Behnke, M.[2020]

This study will investigate the effects of Fecal Microbial Transplantation (FMT) on 42 early-stage ALS patients, aiming to increase the number and function of T regulatory lymphocytes (Tregs) to potentially shift the immune response to a more protective state against ALS progression.

The trial is unique as it is the first to explore FMT as a therapeutic intervention for ALS, with a focus on immunological changes and overall patient outcomes over a 12-month period, including safety and quality of life assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis. Mandrioli, J., Amedei, A., Cammarota, G., et al.[2020]

A case study of a female ALS patient showed that washed microbiota transplantation (WMT) led to significant improvements in her condition over a 12-month follow-up, suggesting a potential new treatment for ALS.

The patient's disease progression was halted after WMT, even after a setback caused by antibiotics, indicating that WMT may help manage ALS symptoms and possibly improve quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: The first case report and narrative review. Lu, G., Wen, Q., Cui, B., et al.[2023]

The gut microbiota of ALS patients shows significant differences compared to matched controls, indicating that microbiota composition may change as the disease progresses, with a notable decrease in microbial diversity over time.

While a 6-month probiotic treatment altered the gut microbiota composition in ALS patients, it did not restore biodiversity to levels seen in healthy controls nor did it impact disease progression as measured by ALSFRS-R.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis. Di Gioia, D., Bozzi Cionci, N., Baffoni, L., et al.[2021]

In a double-blind, placebo-controlled trial involving 126 ALS patients, branched-chain amino acids (BCAA) showed no efficacy in improving disability scales compared to placebo.

The trial was halted due to an observed excess mortality in the BCAA treatment group, raising safety concerns about the use of BCAA in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian ALS Study Group. [2019]

In a one-year double-blind trial involving 22 patients with amyotrophic lateral sclerosis (ALS), those treated with branched-chain amino acids (12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine) maintained muscle strength and walking ability, unlike the placebo group which experienced a decline.

The results suggest that branched-chain amino acids may provide a therapeutic benefit in preserving muscle function in ALS patients, highlighting their potential role in managing this progressive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. Plaitakis, A., Smith, J., Mandeli, J., et al.[2019]

ALS patients show a distinct gut microbiome composition, characterized by increased diversity and a deficiency in Prevotella spp., compared to their spouses, indicating potential microbiome-related factors in the disease.

The study suggests that targeting the gut microbiome, particularly by addressing the deficiency in Prevotella spp. and enhancing butyrate metabolism, could offer new avenues for ALS treatment, as these metabolic pathways were found to be less active in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut microbiome differences between amyotrophic lateral sclerosis patients and spouse controls. Hertzberg, VS., Singh, H., Fournier, CN., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10934997/

Gut-Modulating Agents and Amyotrophic Lateral Sclerosis This review comprehensively summarizes the current literature on ALS-related gut dysbiosis, focusing on the implications of GBA dysfunction.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06051123?cond=Amyotrophic%20lateral%20sclerosis%20and%2For%20frontotemporal%20dementia&viewType=Table&rank=1

Effects of Probiotics in Amyotrophic Lateral Sclerosis ... The aim of this study is to assess the impact of a probiotic formulation on participants with ALS-FTDSD. It is hypothesized that participants given the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10796086/

Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis The experimental results in many animal models of ALS indicate that the dysbiosis of gut microbiota will further worsen ALS diseases. Compared with the SOD1G93A ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06051123;

Effects of Probiotics in Amyotrophic Lateral Sclerosis ... The aim of this study is to assess the impact of a probiotic formulation on participants with ALS-FTDSD. It is hypothesized that participants given the ...

5. mdpi.com mdpi.com/2813-3064/3/1/8

Microbial Influences on Amyotrophic Lateral Sclerosis This review explores the potential role of digestive microbiota and its metabolites in ALS progression and investigates therapeutic approaches targeting gut ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1878747924001569

Gut microbiota immune cross-talk in amyotrophic lateral ... The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling.