Given the role of adaptive immunity in ALS, the pathogenicity of some clostridial strains on motorneurons, the putative role of cyanobacteria in ALS development, and the increasing interest for microbiota in neurodegenerative disorders, the modification of intestinal microbiota might affect ALS at its core. This interventional study aims at evaluating the biological and disease-modifying effects of Fecal Microbiota Transplant (FMT) in patients affected by Amyotrophic Lateral Sclerosis. As a primary aim of the study, the investigators postulate ALS patients treated with FMT compared to the control arm will display increased Tregs number, which is a favourable biomarker of disease activity and progression. Clinical outcomes as disease progression measured by ALS Functional Rating Scale Revised (ALSFRS-R) score, survival, respiratory function and quality of life will be assessed during the whole treatment and follow-up period. Moreover, biological activity of FMT will be evaluated in different biomatrices, together with FMT safety and tolerability in a cohort of ALS patients.
The study will include 42 ALS patients with 2:1 allocation in 2 groups of subjects (28 FMT vs 14 placebo); computerized randomization will be stratified by progression rate (ΔFS)
Inclusion Criteria:
- Patients diagnosed with a laboratory supported, clinically "probable" or "definite"
amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks,
2000)
- Sporadic or familial ALS
- Female or male patients aged between 18 and 70 years old
- Disease duration from symptoms onset no longer than 18 months at the screening visit
- Patients treated with a stable dose of Riluzole (100 mg/day) for at least 30 days
prior to screening
- Patients with a weight > 50 kg and a BMI ≥18
- Patients with a FVC (Forced Vital Capacity) equal or more than 70% predicted normal
value for gender, height, and age at the screening visit
- Patients able and willing to comply with study procedures as per protocol
- Patients able to understand, and capable of providing informed consent at screening
visit prior to any protocol-specific procedures
- Use of effective contraception both for males and females
Exclusion Criteria:
- Known organic gastrointestinal disease
- History of gastrointestinal malignancy; ongoing malignancies
- Use of immunosuppressive or chemotherapy within the past 2 years
- Celiac disease and/or food (e.g.lactose) intolerance
- Previous gastrointestinal surgery
- Any condition that would make endoscopic procedures contraindicated
- Acute infections requiring antibiotics
- Antimicrobial treatment or probiotics 4 weeks prior to screening
- Severe comorbidities (heart, renal, liver failure); severe renal (eGFR<
30ml/min/1.73m2), or liver failure or liver aminotransferase (ALT/AST > 2x Upper
limit of normal),
- Autoimmune diseases, inflammatory disorders (SLE, Rheumatoid arthritis, connective
tissue disorder) or chronic infections (HIV, hepatitis B or C infection)
- Abuse of alcohol or drugs
- HIV, tuberculosis, hepatitis
- Participation in clinical trials <30 days before screening
- Existing blood dyscrasia (e.g., myelodysplasia)
- White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30%
- Patients who underwent non-invasive ventilation, tracheotomy and /or gastrostomy
- Women who are pregnant or breastfeeding