Fecal Microbiota Transplantation Effect on Amyotrophic Lateral Sclerosis Patients

NCT03766321 | Active Not Recruiting DMC

• 1 other identifier: FeTr-ALS
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

microbiota; fecal transplantation; adaptive immunity; T regulatory lymphocytes

Outcome Measures

Primary Outcomes (1)

• Change in Tregs number

  to assess whether FMT increases Tregs' number in ALS patients treated with FMT compared to the control arm

  6 months

Secondary Outcomes (9)

• Change in T cell subsets frequency in blood and gut tissue samples

  12 months (at time points: baseline, month 3 - 6 (both arms)- 9 -12 (both arms))

• Change in heavy neurofilaments levels in CSF

  6 months (at baseline and at month 6)

• Changes in levels of pro-inflammatory cytokines and cytokines linked to T cell proliferation and differentiation

  6 months (at baseline and at month 6)

• Changes in microbiota profile

  12 months (at baseline and at month 6 and 12)

• Incidence of Adverse Events

  12 months ( at screening, baseline, month 1-3-6-7-9-12)

Study Arms (2)

Fecal microbiota transplantation (FMT)

ACTIVE COMPARATOR

Fecal microbiota transplantation will be performed during two endoscopic procedures (at baseline and at 6 months) by allogenic infusion of collected feces in the duodenum-jejunum. Fecal microbiota will be diluted in saline solution 200 ml and infused at 30 ml/minute speed. Every endoscopic procedure will be performed with sedation of the patient. Feces for FMT will be obtained by known healthy donors for C. difficile infection according to standard selection procedures.

Biological: Fecal microbiota transplantation

Placebo

PLACEBO COMPARATOR

ALS patients will undergo upper GI endoscopy with small-intestine biopsies at baseline and after 6 months. Patients in the placebo arm will not receive any treatment during these procedures, but will undergo intestinal biopsy. Every endoscopic procedure will be performed with sedation of the patient.

Biological: Placebo

Interventions

Fecal microbiota transplantation BIOLOGICAL

Fecal microbiota transplantation will be performed during two endoscopic procedures (baseline and at 6 months) by allogenic infusion of collected feces in the duodenum-jejunum.

Also known as: FMT

Fecal microbiota transplantation (FMT)

Placebo BIOLOGICAL

patients will undergo endoscopic procedure with biopsy during sedation but without any kind of intervention

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead
• University of Modena and Reggio Emilia: collaborator
• Catholic University of the Sacred Heart: collaborator
• Campus Bio-Medico University: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• Azienda Ospedaliera di Perugia: collaborator
• University of Chieti: collaborator
• University of Florence: collaborator

Study Sites (5)

Clinica Neurologica, Ospedale Clinicizzato "SS Annunziata"

Chieti, Italy

Location

Azienda Ospedaliero Universitaria di Modena

Modena, Italy

Location

UO Neurofisiopatologia, Azienda Ospedaliera dì Perugia

Perugia, Italy

Location

Catholic University of Sacred Heart - Fondazione Policlinico "A. Gemelli"

Roma, Italy

Location

NEuroMuscular Omnicentre Centre (NeMO), Fondazione Serena Onlus-Fondazione Policlinico A. Gemelli

Roma, Italy

Location

Related Publications (32)

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MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo will be unrecognizable from active treatment because the patients will undergo endoscopic procedure with sedation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: sponsor-investigator

Model Details: randomized double blind multicentre study on FMT in ALS, with a randomization ratio 2:1 (FMT: placebo).

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 6, 2018
• Study Start: July 1, 2020
• Primary Completion: October 1, 2024
• Study Completion: February 1, 2025
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will become available at study completion (after final data analysis)
• Access Criteria: specific personal request by the subject

Locations

IT (5)