Aiming to Reduce Disease-related Gastrointestinal Symptoms in Systemic Sclerosis by Repeat Intestinal Infusions of Anaerobic Cultivated Human Intestinal Microbiome (ACHIM); a Randomized, Double-blind Placebo-controlled 20 Week Study
Overview
- Phase
- Phase 2
- Intervention
- "ACHIM" as solute (10^9 intestinal microbes/ml)
- Conditions
- Systemic Sclerosis
- Sponsor
- Oslo University Hospital
- Enrollment
- 75
- Locations
- 4
- Primary Endpoint
- • Change from baseline to week 12 in UCLA GIT score item diarrhea or bloating, depending which was the worst symptom at baseline evaluated separately for each patient
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study evaluates the effect of intestinal microbiota therapy on gastro-intestinal symptoms in patients with systemic sclerosis (SSc). This is a mulicenter randomized controlled trial conducted at university hospitals in Oslo, Tromsø, Bergen and Trondheim in Norway. In part A1, half of the patients will receive active substance (intestinal microbiota cultured in the lab - "ACHIM") in the small intestine twice by gastroduodenoscopy, the other half will receive placebo. The primary outcome will be measured on week 12 by patient reported outcome measures. In part A2, all participants receive ACHIM at week 12, with an 8 week follow-up for all. A step-wise follow-up will be done in part B up to 16 weeks after week 20 until the last participant finish week 20 visit, which is defined as end of study.The blind from the first intervention will not be opened before end of study.
Investigators
Anna-Maria Hoffmann-Vold
National PI
Oslo University Hospital
Eligibility Criteria
Inclusion Criteria
- •Participant must be 18 to 85 years of age inclusive, at the time of signing the informed consent.
- •Participants must have been clinically diagnosed with SSc by a rheumatologist having experience with the disease.
- •Participants must have disease characteristics that fulfill the 2013 ACR/EULAR classification criteria for SSc.
- •Participants must be able to understand and follow trial procedures including completion of questionnaires regarding Patient Reported Outcome measures, such as the Norwegian version of the UCLA GIT V2.0 score.
- •Participants must have moderate to severe SSc-related lower GI symptoms at time of inclusion, as defined by UCLA GIT score values of ≥1.01 for bloating and/or ≥0.50 for diarrhea at the screening visit.
- •Male and female
- •Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
- •Medical Conditions
- •Cardiovascular diseases, any of the following
- •Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 month of Visit 1
- •Myocardial infarction within 6 months of Visit 1
- •Unstable cardiac angina within 6 months of Visit 1
- •Lung disease with impaired respiratory function, any of the following
- •Forced Vital Capacity (FVC) \< 50% of expected reference value within 12 month of Visit 1
- •Diffusing lung capacity for carbon monoxide (DLCO) \< 40% of expected reference value within 12 month of Visit 1
- •LTOT or lung-tx
- •Significant pulmonary hypertension, any of the following
Arms & Interventions
ACHIM by gastroduodenoscopy
Intestinal microbiota (acronym ACHIM - anaerobically cultured human intestinal microbiota) will be administered by gastroduodenoscope twice (given at baseline and study-week 2). Each with volume 30 ml, containing approximately 10\^9 bacteria / ml. Primary outcome measured at week 12. At week 12 an open label administration of ACHIM to all participants. Thereafter an 8 (+16) week period observation. Blind from the first intervention will be maintained through-out the duration of the study.
Intervention: "ACHIM" as solute (10^9 intestinal microbes/ml)
Placebo by gastroduodenoscopy
ACHIM culture media (no bacteria) will be administered by gastroduodenoscope twice (given at baseline and study-week 2). Each with volume 30 ml. Primary outcome measured at week 12. At week 12 an open label administration of ACHIM to all participants. Thereafter an 8 (+16) week period observation. Blind from the first intervention will be maintained through-out the duration of the study.
Intervention: "ACHIM" as solute (10^9 intestinal microbes/ml)
Outcomes
Primary Outcomes
• Change from baseline to week 12 in UCLA GIT score item diarrhea or bloating, depending which was the worst symptom at baseline evaluated separately for each patient
Time Frame: baseline to week 12
The UCLA GIT score is a validated patient reported outcome measure capturing and grading GI symptoms related to SSc. The bloating scale is scored on a Visual Analog Scale from 0 (better) to 3 (worse) and the diarrhea scale from 0 (better) to 2.5 (worse). Change=(week12 score-baseline score)
Secondary Outcomes
- • Safety and tolerability assessed by adverse event (AE) monitoring, physical examination and clinical laboratory testing from baseline to the end of the study period(• Over the study period of 20 (+16) weeks)
- • Change from baseline to week 12 in total UCLA GIT score(baseline, week 6 and week 12.)
- • Change from baseline to week 12 in UCLA GIT score item diarrhea(baseline to week 12)
- • Change from baseline to week 12 in UCLA GIT score item bloating(baseline to week 12)