drugset / Trial / NCT04300426
Safety and Efficacy of Anaerobic Cultivated Human Intestinal Microbiome Transplantation in Systemic Sclerosis (ReSScue)
Phase 2
Completed
75 enrolled
Oslo University Hospital
Haukeland University Hospital · collabSouth-Eastern Norway Regional Health Authority · collabSt. Olavs Hospital · collabUniversity Hospital of North Norway · collab
RandomizedParallel-groupTriple-blindTreatment
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.
Timeline
- Start
- 2020-09-24
- Primary completion
- 2022-06-27
- Completion
- 2022-06-27
Outcome
Missed primary endpoint
paper Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM PMID 39900089 ↗
paper average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22 PMID 39900089 ↗
paper Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms. PMID 39900089 ↗
Publications
- Background Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, Distler O, Clements P, Cutolo M, Czirjak L, Damjanov N, Del Galdo F, Denton CP, Distler JHW, Foeldvari I, Figelstone K, Frerix M, Furst DE, Guiducci S, Hunzelmann N, Khanna D, Matucci-Cerinic M, Herrick AL, van den Hoogen F, van Laar JM, Riemekasten G, Silver R, Smith V, Sulli A, Tarner I, Tyndall A, Welling J, Wigley F, Valentini G, Walker UA, Zulian F, Muller-Ladner U; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017 Aug;76(8):1327-1339. doi: 10.1136/annrheumdis-2016-209909. Epub 2016 Nov 9.
- Background Hansi N, Thoua N, Carulli M, Chakravarty K, Lal S, Smyth A, Herrick A, Ogunbiyi O, Shaffer J, Mclaughlin J, Denton C, Ong V, Emmanuel AV, Murray CD. Consensus best practice pathway of the UK scleroderma study group: gastrointestinal manifestations of systemic sclerosis. Clin Exp Rheumatol. 2014 Nov-Dec;32(6 Suppl 86):S-214-21. Epub 2014 Nov 5.
- Background Volkmann ER, Hoffmann-Vold AM, Chang YL, Jacobs JP, Tillisch K, Mayer EA, Clements PJ, Hov JR, Kummen M, Midtvedt O, Lagishetty V, Chang L, Labus JS, Molberg O, Braun J. Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts. BMJ Open Gastroenterol. 2017 Apr 1;4(1):e000134. doi: 10.1136/bmjgast-2017-000134. eCollection 2017.
- Background van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.
- Background Staley C, Kaiser T, Vaughn BP, Graiziger C, Hamilton MJ, Kabage AJ, Khoruts A, Sadowsky MJ. Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection. mBio. 2019 Jul 23;10(4):e01586-19. doi: 10.1128/mBio.01586-19.
- Background Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.
- Background Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, Clements PJ, Getzug T, Fathi N, Bechtel A, Furst DE. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009 Sep 15;61(9):1257-63. doi: 10.1002/art.24730.
- Background Khanna D, Furst DE, Maranian P, Seibold JR, Impens A, Mayes MD, Clements PJ, Getzug T, Hays RD. Minimally important differences of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. J Rheumatol. 2011 Sep;38(9):1920-4. doi: 10.3899/jrheum.110225. Epub 2011 Jul 1.
- Background Dehli T, Martinussen M, Mevik K, Stordahl A, Sahlin Y, Lindsetmo RO, Vonen B. Translation and validation of the Norwegian version of the fecal incontinence quality-of-life scale. Scand J Surg. 2011;100(3):190-5. doi: 10.1177/145749691110000310.
- Background Yang Y, Qiu L, Wang L, Xiang X, Tang Y, Li H, Yan F. Quantitative Assessment of Skin Stiffness Using Ultrasound Shear Wave Elastography in Systemic Sclerosis. Ultrasound Med Biol. 2019 Apr;45(4):902-912. doi: 10.1016/j.ultrasmedbio.2018.11.015. Epub 2019 Jan 18.
- Background Benno P, Norin E, Midtvedt T, Hellstrom PM. Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS. Best Pract Res Clin Gastroenterol. 2019 Jun-Aug;40-41:101607. doi: 10.1016/j.bpg.2019.03.003. Epub 2019 Apr 29.
- Background Jorup-Ronstrom C, Hakanson A, Sandell S, Edvinsson O, Midtvedt T, Persson AK, Norin E. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 2012 May;47(5):548-52. doi: 10.3109/00365521.2012.672587. Epub 2012 Apr 2.
- Fretheim H, Barua I, Bakland G, Dhainaut A, Halse AK, Carstens MN, Didriksen H, Midtvedt O, Lundin KEA, Aabakken L, Sarna VK, Zare HK, Khanna D, Distler O, Midtvedt T, Baekkevold ES, Olsen IC, Domanska D, Pesonen ME, Molberg O, Hoffmann-Vold AM. Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2025 May;7(5):e323-e332. doi: 10.1016/S2665-9913(24)00334-5. Epub 2025 Jan 31.
- Hoffmann-Vold AM, Fretheim HH, Sarna VK, Barua I, Carstens MN, Distler O, Khanna D, Volkmann ER, Midtvedt O, Didriksen H, Dhainaut A, Halse AK, Bakland G, Pesonen M, Olsen I, Molberg O. Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial. BMJ Open. 2021 Jun 24;11(6):e048541. doi: 10.1136/bmjopen-2020-048541.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Anaerobic Cultivated Human Intestinal Microbiome | Other / unclassified | 30 ml | Other |