Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Recruiting
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
allogeneic fecal microbiota
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility 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
Sites / Locations
- Pavlov First Saint-Petersburg State Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AutoHSCT + FMT
Arm Description
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)
Outcomes
Primary Outcome Measures
To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis
Multiple sclerosis progression free survival
Secondary Outcome Measures
To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis
Overall survival
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
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
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
Evaluation of Immune system reconstitution after autoHSCT 1
CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT
Evaluation of Immune system reconstitution after autoHSCT 2
Regulatory T-cells (CD4+CD25+CD127low, cell/mm^3) level before and after autoHSCT + FMT
Impact of autoHSCT on brain structure anatomy
MRI 3 Tesla
Full Information
NCT ID
NCT04203017
First Posted
October 30, 2019
Last Updated
July 21, 2022
Sponsor
St. Petersburg State Pavlov Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04203017
Brief Title
Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis
Official Title
Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2019 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Petersburg State Pavlov Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AutoHSCT + FMT
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
allogeneic fecal microbiota
Intervention Description
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 Measure Information:
Title
To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis
Description
Multiple sclerosis progression free survival
Time Frame
365 days
Secondary Outcome Measure Information:
Title
To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis
Description
Overall survival
Time Frame
365 days
Title
To evaluate adverse effects after FMT in immunocompromised patients
Description
Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence
Time Frame
365 days
Title
Quality of life status 1
Description
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
Time Frame
365 days
Title
Quality of life status 2
Description
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
Time Frame
365 days
Title
Evaluation of Immune system reconstitution after autoHSCT 1
Description
CD4+/CD8+ x10^9/l level before and after autoHSCT + FMT
Time Frame
365 days
Title
Evaluation of Immune system reconstitution after autoHSCT 2
Description
Regulatory T-cells (CD4+CD25+CD127low, cell/mm^3) level before and after autoHSCT + FMT
Time Frame
365 days
Title
Impact of autoHSCT on brain structure anatomy
Description
MRI 3 Tesla
Time Frame
365
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Oleg Goloshchapov
Phone
+79219792913
Email
golocht@yandex.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Alexey Polushin, PhD
Phone
+79118167559
Email
alexpolushin@yandex.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boris Afanasyev, Professor
Organizational Affiliation
Pavlov First Saint-Petersburg State Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pavlov First Saint-Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oleg Goloshchapov
Phone
+79219792913
Email
golocht@yandex.ru
First Name & Middle Initial & Last Name & Degree
Alexey Polushin, PhD
Phone
+79118167559
Email
alexpolushin@yandex.ru
First Name & Middle Initial & Last Name & Degree
Alexey Chukhlovin, Professor
First Name & Middle Initial & Last Name & Degree
Ivan Moiseev, PhD, MD
First Name & Middle Initial & Last Name & Degree
Maksim Kucher, PhD, MD
First Name & Middle Initial & Last Name & Degree
Alexey Polushin, PhD
First Name & Middle Initial & Last Name & Degree
Oleg Goloshchapov
12. IPD Sharing Statement
Learn more about this trial
Fecal Microbiota Transplantation After Autologous HSCT in Patients With Multiple Sclerosis
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