Impact of Probiotics on Patients with ALS and Frontotemporal Dementia

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

This study is testing if a probiotic supplement can help people with ALS and frontotemporal dementia feel better and improve their health compared to those who get a placebo.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT06051123 on ClinicalTrials.gov

What this trial studies

This study evaluates the effects of a probiotic formulation on individuals diagnosed with Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Spectrum Disorder (ALS-FTDSD). Participants will be randomly assigned to receive either the probiotics or a placebo over a 24-week intervention period, with assessments of lipid profiles and motor function at multiple time points. The study includes both ALS-FTDSD patients and healthy individuals, with various in-person and phone follow-up visits to collect data through questionnaires and biological samples.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of ALS within the last 24 months.

Not a fit: Patients with advanced ALS or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the role of probiotics in managing ALS-FTDSD and potentially improve patient outcomes.

How similar studies have performed: While the use of probiotics in neurological conditions is an emerging field, this specific approach in ALS-FTDSD is novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Montreal, Quebec

• Centre Hospitalier de l'Université de Montréal — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Genevieve Matte, MDCM, FRCP — Crchum
• Study coordinator: Amélie Bujold, RN

Conditions ALSFTD; ALS; Frontal Temporal Dementia; FTD; motor function; probiotics; lipidomics; metabolites