Effects of Probiotics on Lipidomic Profile and Disease Evolution in ALS-FTDSD Patients: A Randomized Multicenter, Double-blind, Phase II, Placebo-controlled, Parallel Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Change in polar metabolite profiles
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must meet all of the following inclusion criteria to be eligible for enrolment into the study:ALS-FTDSD participants
- •Aged 18 years old or greater.
- •Diagnosis of ALS by El Escorial Criteria revised (possible, probable, probable with lab support and definite).
- •Onset of weakness or speech impairment no more than 24 months before randomization.
- •ALSFRS-R equal or superior to 24/48 at screening, with no more than one subscore under 2/
- •SVC greater than or equal to 60% predicted for sex, age and height at screening.
- •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.
- •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.
- •Participants apt to comprehend and sign the ICF.
- •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
- •Willing to maintain eating habits throughout the study.
- •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:
- •Aged 18 years old or greater.
- •Able to comprehend and willing to sign ICF.
- •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
- •Willing to maintain eating habits throughout the study.
- •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
- •Aged 18 years old or greater.
- •Has frequent and sufficient contact to provide accurate information about the patient's cognitive abilities and behaviors to complete the ALS-CBS.
- •Able to comprehend and willing to sign ICF
排除标准
- •Subjects with any of the following characteristics/conditions will not be included in the study:
- •ALS-FTDSD participants
- •Use of respiratory support (non-invasive ventilation or mechanical respiratory support) at screening.
- •Significant medical condition or behavioral issues that could interfere with participation in the clinical trial in the principal investigator's opinion.
- •Use of a feeding tube at randomization.
- •Use of lipid-lowering drugs for less than 3 months before randomization.
- •Introduction of lipid-lowering drug unless it is due to the event of acute coronary syndrome or stroke as per Canadian guidelines.
- •Use of edaravone with stable dosage for less than 2 months before randomization.
- •Use of riluzole with stable dosage for less than 1 month before randomization.
- •Introduction of edaravone or riluzole during the clinical trial.
- •Immunodeficiency (immune-compromised and immune-suppressed participants, e.g., AIDS, lymphoma, participants undergoing long-term corticosteroid treatment, chemotherapy and allograft participants).
- •Pregnancy (as per serum HCG pregnancy test at screening), planning to be pregnant or currently breastfeeding.
- •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.
- •Use of any antibiotic drug in the month prior to randomization. Note: participants could be eligible to participate after a 4-week washout period.
- •Milk and soy allergy, or severe lactose intolerance.
- •Currently enrolled in another clinical trial.
- •Healthy controls:
- •Use of lipid-lowering drugs for less than 3 months before randomization.
- •Introduction of lipid-lowering drug unless it is due to the event of acute coronary syndrome or stroke as per Canadian guidelines.
- •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.
- •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.
- •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.
- •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.
- •Currently enrolled in another clinical trial.
研究组 & 干预措施
Experimental Group
Participants in this group will be randomized to receive a probiotic formulation for 24 weeks.
干预措施: Probiotic (Dietary Supplement)
Control Group
Participants in this group will be randomized to receive a placebo for 24 weeks.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Change in polar metabolite profiles
时间窗: 24 weeks
To compare the change in polar metabolite profiles from baseline in the probiotic and placebo groups (within-group) as well as in between-group differences over the 24 weeks of intervention. Targets will be key microbiota metabolites: trimethylamine N-oxide (TMAO), short-chain fatty acids, and metabolites derived from tryptophan.
Change in lipidomic profiles
时间窗: 24 weeks
To compare the change in lipidomic profiles from baseline in the probiotic and placebo groups (within-group) as well as in between-group differences 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.
Change in lipids and polar metabolites composition in the plasma of participant
时间窗: 24 weeks
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.
次要结局
- Change in ALSFRS-R score(24 weeks)
- Change in ALS-CBS score(24 weeks)
- Change in ALSAQ-5 scores(24 weeks)
- Fecal microbiota of healthy participants(24 weeks)
- Change in FAB score(24 weeks)
- Lipidomic profiles of healthy participants(24 weeks)
- Change in neurofilament light chain concentration(24 weeks)
- Change in fecal microbiota in ALS-FTDSD patients(24 weeks)
- Polar metabolite profiles of healthy participants(24 weeks)
- Change in ALS Functional Rating Scale Revised (ALSFRS-R) score(24 weeks)