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Gut Microbiota Transplantation in Systemic Sclerosis

Phase 1
Completed
Conditions
Scleroderma, Systemic
Interventions
Biological: Anaerobically Cultivated Human Intestinal Microbiota
Biological: Anaerobically Cultivated medium
Registration Number
NCT03444220
Lead Sponsor
Oslo University Hospital
Brief Summary

Systemic Sclerosis (SSc) is a progressive multi-organ disorder with high disease burden. Life expectancy in SSc is reduced by 25-40 years, mainly due to cardiopulmonary and gastro-intestinal (GI) disease involvement; and a very poor response to available treatment. Aiming to improve treatment for SSc, the ReSScue project will determine the therapeutic potential of standardized, cultivated gut microbiome transplantation (GMT), and assess the mechanisms by which this novel intervention strategy works. This approach is rationalized by studies indicating that skewed gut microbiomes could act as major, environmental risk factors in SSc; and thereby be rational targets for therapeutic manipulation. ReSScue is set up as a 4 months randomized double blind trial involving the University Hospital in Oslo. Trial participants will be recruited from the population-based, nationwide SSc cohort. Intervention will be by GMT or placebo. Primary end point is changes in SSc-related GI parameters , while secondary outcomes include safety, explorative clinical parameters, changes in oral, skin and gut microbiomes, and in immune cell phenotypes.

Detailed Description

This is a randomized, double blind clinical trial testing intervention by standardized GMT. The study cohort will include 10 SSc patients with GI symptoms. Evaluation of end points is at 16 weeks. The trial is set up with six study visits. Patient recruitment, eligibility screening and retrieval of informed consent will be performed at OUS before inclusion. At visit 1, and 6 patients will undergo clinical examination, PFTs, at all visits clinical examination and sampling of biological material.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
10
Inclusion Criteria
  • Fulfillment of the 2013 SSc classification criteria
  • Objective GI involvement and provide informed consent.
Exclusion Criteria
  • Severe organ dysfunction (and risk of procedure related complications
  • Recent exposure to antibiotics

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ACHIMAnaerobically Cultivated Human Intestinal MicrobiotaAnaerobically Cultivated Human Intestinal Microbiota
PlaceboAnaerobically Cultivated mediumAnaerobically Cultivated medium
Primary Outcome Measures
NameTimeMethod
Clinical SSc-related GI parametersThe change in the UCLA GIT score from baseline to week 16 will be evaluated.

The investigators apply a patient-reported outcome measure; the validated UCLA Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA GIT score 2.0) Instrument.

The instrument includes seven multi-item scales: diarrhea, reflux, distention/bloating, fecal soilage, constipation, emotional well-being, and social functioning. Items are scored on a 0-3 range, and a lower value indicates a better health related quality of life. The Total GIT Score is a composite score that includes the total sum of all subgroups except constipation divided by 6. The Total GIT Score ranges from 0-3, and a lower value indicates a better health related quality of life.

Secondary Outcome Measures
NameTimeMethod
Clinical SSc activityThe investigators will assess all the SSc disease activity index measures at study start and week 16 .

Explore the effect of GMT on known clinical outcome measures. The investigators base these assessments on the validated SSc disease activity index which includes a set value for active disease and a definition of change.

Clinical SSc-related GI parametersThe change in the UCLA GIT score from baseline will be evaluated at each study visit (week 0,2,4,8 and 12).

The investigators apply a patient-reported outcome measure; the validated UCLA Scleroderma Clinical Trial Consortium GIT 2.0 (UCLA GIT score 2.0) Instrument.

The instrument includes seven multi-item scales: diarrhea, reflux, distention/bloating, fecal soilage, constipation, emotional well-being, and social functioning. Items are scored on a 0-3 range, and a lower value indicates a better health related quality of life. The Total GIT Score is a composite score that includes the total sum of all subgroups except constipation divided by 6. The Total GIT Score ranges from 0-3, and a lower value indicates a better health related quality of life.

Gut microbiome composition changesThe investigators will assess the gut microbiome weekly from study start to week 16.

It is unknown how the gut microbiome composition changes after GMT and how long these changes persist. We will investigate these aspects, as well as the mechanisms by which ACHIM exert its effects. Specifically, the investigators will address how the intestinal IgA binding to gut commensals and other bacteria is regulated.

Tissue architecture changesThe investigators will analyse tissue architeure in the gut at week 0. 2 and 16. The skin tissue archtecture at week 0 and 16. The immune cell distribution in blood at week 0, 2, 4, 8, 12 and 16.

Explore effects of GMT on tissue architecture in gut and skin, and on immune cell distribution in blood.

Incidence of Treatment-Emergent Adverse Events (Safety)Explore safety of GMT intervention at each study visit (week 0, 2, 4, 8,12 and 16)

We define an adverse event as any untoward medical occurrence that may arise during the study period. The study investigator will fill out a safety form at each study visit (week, 0, 2, 4, 8, 12 and 16). The following questions will be asked: Hospital admission or contact with primary physician since last visit and reason why. Diarrhea, constipation, stomach pain, nausea, vomiting or fever since last study visit. Use of antibiotics since last visit.

Trial Locations

Locations (1)

Oslo University Hospital

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Oslo, Norway

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