Gut Microbiota Transplantation in Systemic Sclerosis

Scleroderma, Systemic Clinical Trial

— ReSScue  

Official title:

Reduce Disease Activity in Systemic Sclerosis by Transplantation of an Anaerobically Cultivated Human Intestinal Microbiota, a Controlled Interventional Pilot Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03444220
• Other study ID #: 2016/1529
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 18, 2018
• Est. completion date: October 15, 2018

Study information

• Verified date: March 2019
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 15, 2018
• Est. primary completion date: May 18, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Biological:
• Anaerobically Cultivated Human Intestinal Microbiota
30ml ACHIM will be administrated at week 0 and 2 with 14 days apart
• Anaerobically Cultivated medium
30ml medium will be administrated at week 0 and 2 with 14 days apart

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical SSc-related GI parameters	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.	The change in the UCLA GIT score from baseline to week 16 will be evaluated.
Secondary	Clinical SSc activity	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.	The investigators will assess all the SSc disease activity index measures at study start and week 16 .
Secondary	Gut microbiome composition changes	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.	The investigators will assess the gut microbiome weekly from study start to week 16.
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety)	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.	Explore safety of GMT intervention at each study visit (week 0, 2, 4, 8,12 and 16)
Secondary	Tissue architecture changes	Explore effects of GMT on tissue architecture in gut and skin, and on immune cell distribution in blood.	The 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.
Secondary	Clinical SSc-related GI parameters	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.	The change in the UCLA GIT score from baseline will be evaluated at each study visit (week 0,2,4,8 and 12).