Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04203017
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : March 18, 2021
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Biological: allogeneic fecal microbiota Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : December 1, 2024

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis [ Time Frame: 365 days ]
    Multiple sclerosis progression free survival


Secondary Outcome Measures :
  1. To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis [ Time Frame: 365 days ]
    Overall survival

  2. 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

  3. 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


  4. 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


  5. Evaluation of Immune system reconstitution after autoHSCT 1 [ Time Frame: 365 days ]
    CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT

  6. 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

  7. Impact of autoHSCT on brain structure anatomy [ Time Frame: 365 ]
    MRI 3 Tesla



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04203017


Contacts
Layout table for location contacts
Contact: Oleg Goloshchapov +79219792913 golocht@yandex.ru
Contact: Alexey Polushin, PhD +79118167559 alexpolushin@yandex.ru

Locations
Layout table for location information
Russian Federation
Pavlov First Saint-Petersburg State Medical University Recruiting
Saint Petersburg, Russian Federation, 197022
Contact: Oleg Goloshchapov    +79219792913    golocht@yandex.ru   
Contact: Alexey Polushin, PhD    +79118167559    alexpolushin@yandex.ru   
Sub-Investigator: Alexey Chukhlovin, Professor         
Sub-Investigator: Ivan Moiseev, PhD, MD         
Sub-Investigator: Maksim Kucher, PhD, MD         
Principal Investigator: Alexey Polushin, PhD         
Principal Investigator: Oleg Goloshchapov         
Sponsors and Collaborators
St. Petersburg State Pavlov Medical University
Investigators
Layout table for investigator information
Principal Investigator: Boris Afanasyev, Professor Pavlov First Saint-Petersburg State Medical University
Layout table for additonal information
Responsible Party: Ivan S Moiseev, Deputy Director for research, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier: NCT04203017    
Other Study ID Numbers: ms/fmt
First Posted: December 18, 2019    Key Record Dates
Last Update Posted: March 18, 2021
Last Verified: March 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases