Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis

Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis

The hypothesis of the study is that according to modern data, the pathogenesis of multiple sclerosis is inextricably linked to the patient's microbiota. Therefore, transplantation of a normal fecal microbiota (FMT) can improve the outcome of autologous hematopoietic stem cell transplantation (autoHSCT) by increasing the disease-free period and disease progression suspension for at least 5 years after transplantation, which meets the NEDA (No Evidence of Disease Activity) criteria, satisfying the current trends of clinical neurology.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: allogeneic fecal microbiota

Detailed Description

AutoHSCT may be a method of choice to treat patients with refractory forms of multiple sclerosis, taking into account the insufficient efficacy of first line therapy, lack of availability (government approval) and high cost of monoclonal antibodies as a second line drugs. In this setting, according to the safety-efficiency ratio the most appropriate are reduced intensity conditioning regimens in autoHSCT. In 75% of cases for refractory forms of multiple sclerosis it is possible to achieve 5 years remission with transplant mortality less than 1%. In recent years, it is quite clear that gut microbiota abnormalities may be one of mechanisms for autoimmune diseases development. Therefore, the correction of gut dysbiosis through FMT from a healthy donor can improve the effectiveness of basic therapies. Currently, FMT is a rapidly developing method of treating intestinal infections associated with multi-resistant bacteria, based on the replacement of the recipient's microbiota by the donor's microbiota.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197022
    • Pavlov First Saint-Petersburg State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis: Multiple sclerosis (Relapsing-Remitting, Secondary-Progressive, Primary-Progressive)
• AutoHSCT
• Signed informed consent
• No second tumors
• No severe concurrent illness
• 1.0-6.5 points by EDSS
• Disease duration less than 20 years
• Disease progression on 1 and/or 2 line therapy (1 point EDSS 1.0-6.0 and 0,5 point EDSS 6.0-6.5)

Exclusion Criteria:

• Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
• Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
• Respiratory distress >grade I
• Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
• Creatinine clearance < 60 mL/min
• Uncontrolled bacterial or fungal infection at the time of enrollment
• Requirement for vasopressor support at the time of enrollment
• Karnofsky index <30%
• Pregnancy
• Somatic or psychiatric disorder making the patient unable to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AutoHSCT + FMT; AutoHSCT with reduced intensity condition regimen (RIC). FMT starting D+60 up to D+120 via po capsules: 30 capsules with fecal transplant divided in two consecutive days (more accurate capsules amount is according to patients body weight)	Biological: allogeneic fecal microbiota; All patients receive autoHSCT with RIC (Cyclophosphamide, Antithymocyte globulin, Rituximab). After immune system reconstitution (approximately starting D+60 up to D+120), patients will receive FMT from healthy donor via po capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis	Multiple sclerosis progression free survival	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis	Overall survival	365 days
To evaluate adverse effects after FMT in immunocompromised patients	Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence	365 days
Quality of life status 1	Multiple sclerosis-specific questionnaire - HADS (Hospital Anxiety and Depression Scale) before and after autoHSCT: 0-7 points - normal; 8-10 - subclinically expressed anxiety/depression; 11-21 - clinically expressed anxiety/depression	365 days
Quality of life status 2	Multiple sclerosis-specific questionnaire - EDSS (Expanded Disability Status Scale) before and after autoHSCT: 0 points - Normal neurologic exam; 1.0-1.5 - No disability, minimal signs in one or two Functional Systmes (FS); 2.0-2.5 - Minimal disability in one or two FS; 3.0-3,5 - Moderate disability in one FS, fully ambulatory; 4.0-4.5 - Fully ambulatory without aid. Able to walk without aid or rest some 500 or 300 meters; 5.0-5.5 - Ambulatory without aid or rest for about 200 or 100 meters; 6.0 - Intermittent assistance required to walk about 100 meters; 6.5 - Constant bilateral assistance required to walk about 20 meters; 7.0-7.5 - Unable to walk beyond about 5 meters or more than a few steps; 8.0 - Essentially restricted to bed, but may be out of bed itself; 8.5 - Essentially restricted to bed; 9.0 - Helpless bed patient; can communicate and eat; 9.5 - Totally helpless bed patient; unable to communicate effectively or eat/swallow; 10 - Death due to MS	365 days
Evaluation of Immune system reconstitution after autoHSCT 1	CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT	365 days
Evaluation of Immune system reconstitution after autoHSCT 2	Regulatory T-cells (CD4+CD25+CD127low, cell/mm^3) level before and after autoHSCT + FMT	365 days
Impact of autoHSCT on brain structure anatomy	MRI 3 Tesla	365

Collaborators and Investigators

• Sponsor: St. Petersburg State Pavlov Medical University
• Investigators: Principal Investigator: Boris Afanasyev, Professor, Pavlov First Saint-Petersburg State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): November 29, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: December 15, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: ms/fmt

Drug and device information, study documents

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