Effects of Probiotics in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Spectrum Disorder (ALS-FTDSD) Patients (PROBIOTIC)

Effects of Probiotics on Lipidomic Profile and Disease Evolution in ALS-FTDSD Patients: A Randomized Multicenter, Double-blind, Phase II, Placebo-controlled, Parallel 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.

Study Overview

• Status: Recruiting
• Conditions: ALS (Amyotrophic Lateral Sclerosis); Frontal Temporal Dementia (FTD); ALSFTD
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotic

Detailed Description

Individuals with ALS-FTDSD, their caregivers and healthy individuals can participate in this randomized, double-blind, parallel, placebo-controlled study. Participants will be enrolled for a period of 32 weeks, with an intervention period of 24 weeks. For ALS-FTDSD participants, there will be 9 visits during the intervention (5 in-person and 4 phone calls) and 1 follow-up call post-intervention. For healthy participants, there will be 4 in-person visits. For all participants, in-person visits will involve filling out questionnaires, giving blood samples, and returning stool samples.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amélie Bujold, RN; Phone Number: 13616 514-890-8000; Email: amelie.bujold.chum@ssss.gouv.qc.ca
• Study Contact Backup: Name: Richard Miallot, PhD; Phone Number: 13616 514-890-8000; Email: richard.miallot.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 0C7
      • Recruiting
      • Stan Cassidy Centre for Rehabilitation
      • Contact: Susan McCully, RN MN; Phone Number: (506) 471-9924; Email: Susan.mccully@horizonnb.ca
      • Principal Investigator: Colleen O'Connell, MD, FRCPC
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Recruiting
      • Centre Hospitalier de l'Universite de Montreal
      • Principal Investigator: Genevieve Matte, MD
      • Sub-Investigator: Alex Parker, Ph.D.
      • Sub-Investigator: Stephan Botez, MD, FRCPC
      • Contact: Amélie Bujold, RN; Phone Number: 13616 5148908000; Email: amelie.bujold.chum@ssss.gouv.qc.ca
      • Contact: Richard Miallot, PhD; Phone Number: 13616 5148908000; Email: richard.miallot.chum@ssss.gouv.qc.ca
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Recruiting
      • University of Saskatchewan, Clinical Trials Support Unit
      • Contact: Janet Peters, Clinical Research Coordinator, RN; Phone Number: +1 639 317 5899; Email: janet.peters@usak.ca
      • Contact: Joanne Boyer, RN; Phone Number: +1 306 280 8001; Email: joanne.boyer@usak.ca
      • Principal Investigator: Kerri Schellenberg, MD, FRCPC
      • Sub-Investigator: Ryan Verity, MD, FRCPC, CSCN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

Participants must meet all of the following inclusion criteria to be eligible for enrolment into the study:ALS-FTDSD participants

1. Aged 18 years old or greater.
2. Diagnosis of ALS by El Escorial Criteria revised (possible, probable, probable with lab support and definite).
3. Onset of weakness or speech impairment no more than 24 months before randomization.
4. ALSFRS-R equal or superior to 24/48 at screening, with no more than one subscore under 2/4.
5. SVC greater than or equal to 60% predicted for sex, age and height at screening.
6. Note on FTD Symptoms: The presence of FTD symptoms is not a requirement for inclusion in this study. Participants with a diagnosis of ALS, whether or not accompanied by FTD symptoms, are eligible for inclusion. No prior or screening diagnosis of FTDSD is required.
7. Subject has an informant/caregiver who has frequent and sufficient contact to provide accurate information about the patient's cognitive abilities and behaviors to complete the ALS-CBS.
8. Participants apt to comprehend and sign the ICF.

9. Participants of child-bearing potential must have a negative serum pregnancy test at screening and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

   • Abstinence or agrees to use contraception if planning to become sexually active.
   • Hormonal contraceptives including oral contraceptives, hormone birth control patch, vaginal contraceptive ring, injectable contraceptives, or hormone implant
   • Double-barrier method
   • Intrauterine devices
   • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
   • Vasectomy of partner at least 6 months prior to screening
10. Willing to maintain eating habits throughout the study.
11. Willing to refrain from consuming probiotic supplements and food containing added probiotics and/or prebiotics (e.g., yogurts with live, active cultures or supplements) from the moment of screening until the end of the study.

Healthy controls:

1. Aged 18 years old or greater.
2. Able to comprehend and willing to sign ICF.

3. Participants of child-bearing potential must have a negative serum pregnancy test at screening and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

   • Abstinence or agrees to use contraception if planning to become sexually active.
   • Hormonal contraceptives including oral contraceptives, hormone birth control patch, vaginal contraceptive ring, injectable contraceptives, or hormone implant
   • Double-barrier method
   • Intrauterine devices
   • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
   • Vasectomy of partner at least 6 months prior to screening
4. Willing to maintain eating habits throughout the study.
5. Willing to refrain from consuming probiotic supplements and food containing added probiotics and/or prebiotics (e.g., yogurts with live, active cultures or supplements) from the moment of screening until the end of the study.

Informant/caregiver

1. Aged 18 years old or greater.
2. Has frequent and sufficient contact to provide accurate information about the patient's cognitive abilities and behaviors to complete the ALS-CBS.
3. Able to comprehend and willing to sign ICF

Exclusion criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

ALS-FTDSD participants

1. Use of respiratory support (non-invasive ventilation or mechanical respiratory support) at screening.
2. Significant medical condition or behavioral issues that could interfere with participation in the clinical trial in the principal investigator's opinion.
3. Use of a feeding tube at randomization.
4. Use of lipid-lowering drugs for less than 3 months before randomization.
5. Introduction of lipid-lowering drug unless it is due to the event of acute coronary syndrome or stroke as per Canadian guidelines.
6. Use of edaravone with stable dosage for less than 2 months before randomization.
7. Use of riluzole with stable dosage for less than 1 month before randomization.
8. Introduction of edaravone or riluzole during the clinical trial.
9. Immunodeficiency (immune-compromised and immune-suppressed participants, e.g., AIDS, lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participants).
10. Pregnancy (as per serum HCG pregnancy test at screening), planning to be pregnant or currently breastfeeding.
11. Use of probiotics other than the study medication in the month prior to randomization. Note: participants could be eligible to participate after a 4-week washout period.
12. Use of any antibiotic drug in the month prior to randomization. Note: participants could be eligible to participate after a 4-week washout period.
13. Milk and soy allergy, or severe lactose intolerance.
14. Currently enrolled in another clinical trial.

Healthy controls:

1. Use of lipid-lowering drugs for less than 3 months before randomization.
2. Introduction of lipid-lowering drug unless it is due to the event of acute coronary syndrome or stroke as per Canadian guidelines.
3. Pregnancy (as per serum HCG pregnancy test at screening), planning to be pregnant or currently breastfeeding. Note: participants will not take the IP or placebo, but pregnancy is a major factor that could affect lipidomic profiling.
4. Use of probiotics in the month prior to day 0 of the study (visit 2). Note: participants could be eligible to participate after a 4-week washout period. Although participants will not consume any study product, we aim to maintain environmental factors comparable to the ALS-FTDSD group.
5. Use of any antibiotic drug in the month prior to day 0 of the study (visit 2). Note: participants could be eligible to participate after a 4-week washout period. Although participants will not consume any study product, we aim to maintain environmental factors comparable to the ALS-FTDSD group.
6. Milk and soy allergy, or severe lactose intolerance. Note: Although participants will not consume any study product, we aim to maintain environmental factors comparable to the ALS-FTDSD group. We aim to exclude allergies, so participants are maintained on standard diet.
7. Currently enrolled in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Participants in this group will be randomized to receive a probiotic formulation for 24 weeks.	Dietary supplement: Probiotic; Participants will be taking 1 sachet a day.
Placebo Comparator: Control Group; Participants in this group will be randomized to receive a placebo for 24 weeks.	Dietary supplement: Placebo; Participants will be taking 1 sachet a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lipids and polar metabolites composition in the plasma of participant	Metabolomics will provide a quantitative and qualitative assesment of the lipidomic and polar metabolite profiles of participants on the probiotic arm and the participants on the placebo arm. Participants will be assessed at week 0, at week 12 and then at the end of the investigation period at week 24.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ALS-CBS score	To compare the average change from baseline in ALS Cognitive Behavioral Screen (ALS-CBS) and Frontal Assessment Battery (FAB) between the probiotic and placebo groups over the 24 weeks of intervention.	24 weeks
Change in neurofilament light chain concentration	To compare the average change from baseline in the neurofilament light chain concentration between the probiotic and placebo groups over the 24 weeks of intervention.	24 weeks
Change in ALSAQ-5 scores	To compare the average change from baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-5 (ALSAQ-5) between the probiotic and placebo groups over the 24 weeks of intervention.	24 weeks
Change in fecal microbiota in ALS-FTDSD patients	To compare the fecal microbiota composition, diversity, and strain recovery over the 24 weeks of intervention in the probiotic and placebo groups. Techniques will be based on the extraction of DNA and amplification of 16S ribosomal RNA genes. These genes are highly conserved between bacterial species, but vary in a manner that allows species identification.	24 weeks
Lipidomic profiles of healthy participants	To explore lipidomic profiles from baseline in healthy participants over the 24 weeks of intervention. This will be a lipid profiling and quantification by using mass-spectrometry-based lipidomics. We are going to test 900 different lipids, which can be classified in 20 classes ans subclasses of interest.	24 weeks
Change in ALS Functional Rating Scale Revised (ALSFRS-R) score	Participants' ALS Functional Rating Scale Revised (ALSFRS-R) score, following intake of the probiotic or placebo. Participants will be assessed at week 0, at week12 and then at the end of the investigation period at week 24.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of AEs and SAEs	To compare the number of adverse events (AEs) and serious adverse events (SAEs) that occur among to the probiotic group versus the placebo group throughout the study.	28 weeks
Changes in lab safety marker: Complete Blood Count (CBC)	Changes (outside normal variation) in safety lab marker: Complete Blood Count (CBC).	24 weeks
Changes in lab safety markers: Liver Function Test (LFT) - ALT	Changes (outside normal variation) in safety lab markers :Liver Function Tests (LFTs), more precisely alanine transaminase (ALT).	24 weeks
Changes in lab safety markers: Liver Function Test (LFT) - AST	Changes (outside normal variation) in safety lab markers :Liver Function Tests (LFTs), more precisely aspartate transaminase (AST).	24 weeks
Changes in lab safety markers: Liver Function Test (LFT) - bilirubin	Changes (outside normal variation) in safety lab markers :Liver Function Tests (LFTs), more precisely total bilirubin.	24 weeks
Changes in lab safety marker: creatinine	Changes (outside normal variation) in safety lab marker: creatinine.	24 weeks

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Lallemand Health Solutions
• Investigators: Principal Investigator: Genevieve Matte, MDCM, FRCP, CRCHUM

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 11, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: ALS; probiotics; microbiome; metabolites; lipidomics; motor function; FTD; neurofilament
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia With Motor Neuron Disease; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Probiotics
• Other Study ID Numbers: 2024-11453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No