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Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT04203017
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : July 22, 2022
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

Tracking Information
First Submitted Date  ICMJE October 30, 2019
First Posted Date  ICMJE December 18, 2019
Last Update Posted Date July 22, 2022
Actual Study Start Date  ICMJE June 1, 2019
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2019)		 To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis [ Time Frame: 365 days ]
Multiple sclerosis progression free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis [ Time Frame: 365 days ]
    Overall survival
  • To evaluate adverse effects after FMT in immunocompromised patients [ Time Frame: 365 days ]
    Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence
  • Quality of life status 1 [ Time Frame: 365 days ]
    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
  • Quality of life status 2 [ Time Frame: 365 days ]
    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
  • Evaluation of Immune system reconstitution after autoHSCT 1 [ Time Frame: 365 days ]
    CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT
  • Evaluation of Immune system reconstitution after autoHSCT 2 [ Time Frame: 365 days ]
    Regulatory T-cells (CD4+CD25+CD127low, cell/mm^3) level before and after autoHSCT + FMT
  • Impact of autoHSCT on brain structure anatomy [ Time Frame: 365 ]
    MRI 3 Tesla
Original Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2019)
  • To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis [ Time Frame: 365 days ]
    Overall survival
  • To evaluate adverse effects after FMT in immunocompromised patients [ Time Frame: 365 days ]
    Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence
  • Quality of life status 1 [ Time Frame: 365 days ]
    Multiple sclerosis-specific questionnaire - HADS before and after autoHSCT
  • Quality of life status 2 [ Time Frame: 365 days ]
    Multiple sclerosis-specific questionnaire - PASSAT before and after autoHSCT
  • Evaluation of Immune system reconstitution after autoHSCT 1 [ Time Frame: 365 days ]
    CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT
  • Evaluation of Immune system reconstitution after autoHSCT 2 [ Time Frame: 365 days ]
    Regulatory T-cells (CD4+CD25+CD127low, cell/mm^3) level before and after autoHSCT + FMT
  • Impact of autoHSCT on brain structure anatomy [ Time Frame: 365 ]
    MRI 3 Tesla
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis
Official Title  ICMJE Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE 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.
Study Arms  ICMJE 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)
Intervention: Biological: allogeneic fecal microbiota
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 15, 2019)		 20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2024
Estimated Primary Completion Date June 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Oleg Goloshchapov +79219792913 golocht@yandex.ru
Contact: Alexey Polushin, PhD +79118167559 alexpolushin@yandex.ru
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04203017
Other Study ID Numbers  ICMJE ms/fmt
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Ivan S Moiseev, St. Petersburg State Pavlov Medical University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE St. Petersburg State Pavlov Medical University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Boris Afanasyev, Professor Pavlov First Saint-Petersburg State Medical University
PRS Account St. Petersburg State Pavlov Medical University
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP