Gut Microbiota Transplantation in Systemic Sclerosis

NCT03444220 | Completed Phase 1

• 1 other identifier: 2016/1529
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Scleroderma, Systemic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Clinical SSc activity

  The investigators will assess all the SSc disease activity index measures at study start and week 16 .

• Gut microbiome composition changes

  The investigators will assess the gut microbiome weekly from study start to week 16.

• Incidence of Treatment-Emergent Adverse Events (Safety)

  Explore safety of GMT intervention at each study visit (week 0, 2, 4, 8,12 and 16)

• Tissue architecture changes

  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.

• Clinical SSc-related GI parameters

  The change in the UCLA GIT score from baseline will be evaluated at each study visit (week 0,2,4,8 and 12).

Study Arms (2)

ACHIM

ACTIVE COMPARATOR

Anaerobically Cultivated Human Intestinal Microbiota

Biological: Anaerobically Cultivated Human Intestinal Microbiota

Placebo

PLACEBO COMPARATOR

Anaerobically Cultivated medium

Biological: Anaerobically Cultivated medium

Interventions

Anaerobically Cultivated Human Intestinal Microbiota BIOLOGICAL

30ml ACHIM will be administrated at week 0 and 2 with 14 days apart

ACHIM

Anaerobically Cultivated medium BIOLOGICAL

30ml medium will be administrated at week 0 and 2 with 14 days apart

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fulfillment of the 2013 SSc classification criteria
• Objective GI involvement and provide informed consent.

You may not qualify if:

• Severe organ dysfunction (and risk of procedure related complications
• Recent exposure to antibiotics

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0372, Norway

Location

Related Publications (1)

• Strahm N, Didriksen H, Fretheim H, Molberg O, Midtvedt O, Farstad IN, Midtvedt T, Lundin KEA, Aabakken L, Blyszczuk P, Distler O, Kania G, Hoffmann-Vold AM. Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis. Rheumatology (Oxford). 2023 Aug 1;62(8):2918-2929. doi: 10.1093/rheumatology/kead014.

  PMID: 36688692 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Anna-Maria Hoffmann-Vold, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: February 23, 2018
• Study Start: January 18, 2018
• Primary Completion: May 18, 2018
• Study Completion: October 15, 2018
• Last Updated: March 13, 2019

Record last verified: 2019-03

Locations

NO (1)