Clinical trial NCT04203017: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Sclerosis
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2019-12-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis
timeFrame: 365 days
Secondary outcomes:
measure: To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis
timeFrame: 365 days
measure: To evaluate adverse effects after FMT in immunocompromised patients
timeFrame: 365 days
measure: Quality of life status 1
timeFrame: 365 days
measure: Quality of life status 2
timeFrame: 365 days
measure: Evaluation of Immune system reconstitution after autoHSCT 1
timeFrame: 365 days
measure: Evaluation of Immune system reconstitution after autoHSCT 2
timeFrame: 365 days
measure: Impact of autoHSCT on brain structure anatomy
timeFrame: 365
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint-Petersburg State Medical University
Study officials:
affiliation: Pavlov First Saint Petersburg State Medical University
name: Boris Afanasyev, Professor
role: PRINCIPAL_INVESTIGATOR
References: