Probiotics for ALS (PROBIOTIC Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByGenevieve Matte, MDCM, FRCP
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Trial Summary
What is the purpose of this trial?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 probiotics will have different lipid profiles compared to participants receiving the placebo at different time points.
What safety data exists for probiotics in ALS treatment?The provided research does not directly address the safety data for probiotics in ALS treatment. However, it mentions a study on the impact of probiotic supplementation on gut microbiota and disease progression in ALS patients, suggesting ongoing research in this area. No specific safety concerns or adverse effects related to probiotics are reported in the abstracts provided.12456
What data supports the idea that Probiotics for ALS is an effective treatment?The available research shows that probiotics might help ALS patients by improving gut health and possibly slowing disease progression. One study found that ALS patients who took probiotics with high glutamine synthetase activity had a slower decline in their condition compared to those who didn't. Another study suggested that altering the gut microbiome, such as by addressing deficiencies in certain bacteria, could be beneficial for ALS treatment. However, these findings are preliminary and need further validation.14567
Is the treatment Probiotic a promising treatment for ALS?Yes, probiotics, which are beneficial bacteria, show promise as a treatment for ALS. Research suggests that altering gut bacteria can impact ALS progression, and probiotics may help improve the gut environment, potentially slowing the disease.13468
Do I have to stop taking my current medications for the trial?The trial does not specify that you must stop all current medications. However, you cannot start or change the dosage of edaravone, riluzole, or ALBRIOZA™ during the trial. If you are using lipid-lowering drugs, they must have been stable for at least 3 months before randomization. If you have used probiotics or antibiotics in the month prior, you need a 4-week washout period before joining. Please consult with the trial team for specific guidance on your medications.
Eligibility Criteria
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
I am 18 years old or older.
I have been diagnosed with ALS according to specific criteria.
My lung function test scores are normal for my age, sex, and height.
I am using a form of hormonal birth control.
Exclusion Criteria
I use a machine to help me breathe.
I have a weakened immune system due to a condition like AIDS or treatments like chemotherapy.
I will start taking edaravone, riluzole, or ALBRIOZA™ during the trial.
I am using a feeding tube.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Experimental GroupExperimental Treatment1 Intervention
Participants in this group will be randomized to receive a probiotic formulation for 24 weeks.
Group II: Control GroupPlacebo Group1 Intervention
Participants in this group will be randomized to receive a placebo for 24 weeks.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Centre Hospitalier de l'Université de MontréalMontréal, Canada
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Who is running the clinical trial?
Centre hospitalier de l'Université de Montréal (CHUM)Lead Sponsor
Lallemand Health SolutionsIndustry Sponsor
References
Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. [2019]22 patients with amyotrophic lateral sclerosis were entered into a double-blind, randomised, placebo-controlled trial of treatment with branched-chain aminoacids. 11 received daily 12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine, by mouth, and the remainder received placebo. During the one-year trial, patients in the placebo group showed a linear decline in functional status consistent with the natural history of the disease. Those treated with aminoacids showed significant benefit in terms of maintenance of extremity muscle strength and continued ability to walk.
Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian ALS Study Group. [2019]We initiated a double-blind, placebo-controlled trial to test the efficacy and safety of branched-chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 6 g, and L-valine 6 g daily) in amyotrophic lateral sclerosis (ALS) patients. There was an excess mortality in subjects randomized to active treatment (24 BCAA, 13 placebo) when a total of 126 ALS patients had been recruited. This finding, associated with the lack of efficacy of BCAA (measured by comparing the disability scales in the two treatment groups), led the Data Monitoring Committee to require cessation of the trial.
Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis. [2019]Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS. Here we present evidence that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology.
FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis. [2020]Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity. Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life. Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course. Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage.
Theme 6 Tissue biomarkers. [2020]Background: Glutamate excitotoxicity is a longstanding hypothesis in the pathophysiology of ALS. Prior studies have demonstrated increased plasma glutamate levels in ALS patients, which suggest a systemic defect in glutamate metabolism (1). The most abundant amino acid consumed in our diet is glutamate. Studies in healthy human subjects have demonstrated efficient metabolism of dietary glutamate via metabolism by enzymes present in the liver, gut lumen and residential gut bacteria. There is increasing evidence that the gut microbiota has significant CNS effects and intestinal dysbiosis has been found in the ALS transgenic SOD1G93A mouse model (2). If intestinal dysbiosis altered the prevalence of glutamine synthetase (GS) producing bacteria, dietary glutamate homeostasis could be impaired, leading to elevated plasma glutamate levels.Objectives: This study examined the degree of fluctuation in plasma glutamate levels seen with consumption of a protein shake in a cohort of ALS patients and family members from a single ALS center.Methods: Twenty six patients (87% of total cohort followed in the ALS center) underwent measurement of plasma amino acid analysis prior to and 1 hour following consumption of a 75 gm protein shake. A subset of 16 patients went on to receive a probiotic with high GS activity and completed serial protein challenges and amino acid analysis during the study. Ten unaffected family members of ALS patients underwent a similar protein challenge. Glutamate Metabolism Dysfunction (GMD) was defined as >30 umol difference post-prandially compared to fasting, and graded as mild (>30-60), moderate (>60-90) or severe (>90).Results: At baseline, 65.4% (17/26) ALS patients screened were GMD positive, compared to 30% (3/10) of tested family members. The severity of GMD in ALS patients was 41% mild, 29% moderate, 29% severe with only mild severity identified in family members. In the six month treatment phase, 75% (6/8) of patients with stable or improving GMD status saw significant improvements in their ALSFRS-R rate of decline, while 71.4% (5/7) with worsening or remaining severe GMD status experienced worsening of their rate of progression.Discussion and conclusions: Although limited by small sample size, this study does represent an excellent sampling within a single ALS center and is the first of its kind to investigate whether impairment in dietary glutamate metabolism exists in ALS patients. If validated in a larger ALS population, detection of glutamate metabolism dysfunction (GMD) could represent a novel biomarker linked to a potential therapeutic target in ALS patients. Planned microbiome analysis will also help in validating this hypothesis.
A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis. [2021]A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression.
Gut microbiome differences between amyotrophic lateral sclerosis patients and spouse controls. [2023]Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is incurable and ultimately fatal. Few therapeutic options are available to patients. In this study, we explored differences in microbiome composition associated with ALS. Methods: We compared the gut microbiome and inflammatory marker profiles of ALS patients (n = 10) to those of their spouses (n = 10). Gut microbiome profiles were determined by 16S rRNA gene sequencing. Results: The gut microbial communities of the ALS patients were more diverse and were deficient in Prevotella spp. compared with those of their spouses. In contrast, healthy couples (n = 10 couples of the opposite sex) recruited from the same geographic region as the patient population did not exhibit these differences. Stool and plasma inflammatory markers were similar between ALS patients and their spouses. Predictive analysis of microbial enzymes revealed that ALS patients had decreased activity in several metabolic pathways, including carbon metabolism, butyrate metabolism, and systems involving histidine kinase and response regulators. Conclusions: ALS patients exhibit differences in their gut microbial communities compared with spouse controls. Our findings suggest that modifying the gut microbiome, such as via amelioration of Prevotella spp. deficiency, and/or altering butyrate metabolism may have translational value for ALS treatment.
Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: The first case report and narrative review. [2023]Amyotrophic lateral sclerosis (ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons, and has an average survival time of three to five years. Growing evidence has suggested a bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS, who benefited from washed microbiota transplantation (WMT), an improved fecal microbiota transplantation (FMT), through a transendoscopic enteral tube during a 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics that caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with a quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.