AzTrials
AzTrials

Systemic SclerosisPhase 2ReSScueNCT04300426

Safety and Efficacy of Anaerobic Cultivated Human Intestinal Microbiome Transplantation in Systemic Sclerosis (ReSScue)

A Phase 2 study testing "ACHIM" as solute (10^9 intestinal microbes/ml) in people with Systemic Sclerosis, run by Oslo University Hospital at 4 sites in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Systemic Sclerosis
What is being tested?
"ACHIM" as solute (10^9 intestinal microbes/ml)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
75 participants
Where
4 sitesNorway
Study dates
24 Sep 2020to 27 Jun 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 44Show fewer
  • 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
  • Previous clinical or echocardiographic evidence of significant right heart failure
  • History of right heart catheterisation showing a cardiac index ≤ 2 l/min/m²
  • History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1
  • Severe anemia with Hb < 8.0 g/l within 4 weeks prior to Visit 1. Repeat testing of Hb is allowed.
  • Bleeding risk, any of the following
  • History of hemorrhagic central nervous system (CNS) event within 12 months of Visit 1.
  • Known genetic predisposition to bleeding
  • Platelet counts < 50 x 109/l
  • Chronic liver disease or gastro-intestinal condition, any of the following
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
  • Decompensated chronic liver disease
  • Inflammatory bowel disease
  • Celiac disease treated for less than 12 months.
  • Gastro-intestinal surgery performed within the within 12 months of Visit 1
  • Hepatic dysfunction, as defined as AST, ALT or bilirubin levels >3 times the Upper limit of normal range (x ULN) within 4 weeks prior to Visit 1. Repeat testing of AST, ALT and bilirubin are allowed in participants with no prior history of hepatic dysfunction.
  • Chronic renal insufficiency, with estimated Glomerular Filtration Rate (eGFR) < 30.
  • Active digital ulcers within 4 weeks of Visit 1.
  • Anaphylactic food allergy.
  • Eating disorder diagnosed by a physician
  • Other diseases or conditions that may interfere with testing procedures (for example inability to conduct gastroduodenoscopy) or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial (for example severe GI symptoms due to other diseases than SSc).
  • Prior/Concomitant Therapy
  • Any antibiotic therapy within 3 months of Visit 1
  • Prednisone >10 mg/day or equivalent within 4 weeks prior to Visit 1
  • Cyclophosphamide or rituximab treatment within 6 months prior to Visit 1
  • Unstable background monotherapy with any of the following therapeutics; mycophenolate mofetil/sodium, methotrexate, azathioprine, tocilizumab, abatacept, leflunomide, tacrolimus, tofacitinib and cyclosporine A. Participants have to be on stable monotherapy with any of these medications for at least 6 months prior to visit 1
  • Combined therapy of two or more of the following therapeutics: mycophenolate mofetil/sodium, methotrexate, azathioprine, tocilizumab, abatacept, leflunomide, tacrolimus, tofacitinib and ciclosporine A within at least 8 weeks prior to visit 1.
  • Need for full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors or heparin)
  • Previous hematopoietic stem cell transplantation (HSCT) within 12 months of Visit 1, or HSCT planned within 12 months after Visit 1.
  • Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit.
  • Prior/Concurrent Clinical Study Experience
  • Prior participation in FMT study in the last 12 months. Diagnostic assessments
  • Abnormal coagulation parameters as defined as International normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN at Visit 1 Other Exclusions
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial. (Women of child bearing potential should be tested with Hcg (urine or serum). Woman of child bearing potential if not using highly efficient contraception.

Trial locations and contacts

4 sites in 1 country.

Norway4 sites

  • Haukeland University Hospital

    Bergen

  • Oslo University Hospital

    Oslo

  • University hospital of North Norway

    Tromsø

  • St. Olavs hospital, Trondheim university hospital

    Trondheim

Other trials in Norway

About this study

Official title: 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

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.

Being tested
"ACHIM" as solute (10^9 intestinal microbes/ml)
Medical subject headings
Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • "ACHIM" as solute (10^9 intestinal microbes/ml)Drug

    Also called Fecal microbiota transplantation

    Culture of intesinal microbiota originally derived from a healthy subject are administered to a person with presumed dysbiotic intestinal symptoms with an objective to treat these symptoms.

Study groups in NCT04300426
Study groupRoleWhat they receive
ACHIM by gastroduodenoscopyExperimentalIntestinal 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.
Receives: Drug: "ACHIM" as solute (10^9 intestinal microbes/ml)
Placebo by gastroduodenoscopyPlacebo comparatorACHIM 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.
Receives: Drug: "ACHIM" as solute (10^9 intestinal microbes/ml)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. • 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

    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)

    Measured: baseline to week 12

Secondary outcomes (4)

  1. • Safety and tolerability assessed by adverse event (AE) monitoring, physical examination and clinical laboratory testing from baseline to the end of the study period

    • Registration of number of adverse events adverse event (AE), assessment of physical examination and clinical laboratory testing by standardized assessments and sampling

    Measured: • Over the study period of 20 (+16) weeks

  2. • Change from baseline to week 12 in total UCLA GIT score

    The UCLA GIT score is a validated patient reported outcome measure capturing and grading GI symptoms related to SSc. The total scale is scored on a Visual Analog Scale from 0 (better) to 3 (worse). Change=(week12 score-baseline score)

    Measured: baseline, week 6 and week 12.

  3. • Change from baseline to week 12 in UCLA GIT score item diarrhea

    The UCLA GIT score is a validated patient reported outcome measure capturing and grading GI symptoms related to SSc. The diarrhea scale is scored on a Visual Analog Scale from 0 (better) to 2.5 (worse) . Change=(week12 score-baseline score)

    Measured: baseline to week 12

  4. • Change from baseline to week 12 in UCLA GIT score item bloating

    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) . Change=(week12 score-baseline score)

    Measured: baseline to week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2020
  2. Study start24 Sep 2020
  3. Primary completion27 Jun 2022
  4. Study completion27 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The 20-week study period consists of a 12-week induction phase (Part A1), with randomized, double-blind parallel group interventions by endoscopic infusions at weeks 0 and 2, and an 8-week maintenance phase (Part A2) where all participants receive one single open label endoscopic infusion on week 12. Additionally, all participants who complete the 20-week study period are followed for a maximum 16 weeks monitoring period (Part B) to obtain longer-term data on safety and durability of intervention effects.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04300426
Sponsor's protocol ID
2019-004400-35
Other IDs
2019
Acronym
ReSScue
Status last verified
Oct 2022
First submitted
25 Feb 2020
Last updated
12 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The investigators plan to publish the protocol and statistical analysis plan separately. The IPD will be published according to relevant legislation and as required by publishing authority.

Publications

  • 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.

    PubMed 27941129

  • 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.

    PubMed 25372804

  • 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.

    PubMed 28761687

  • 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.

    PubMed 23323867

  • 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.

    PubMed 31337728

  • 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.

    PubMed 29860912

  • 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.

    PubMed 19714600

  • 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.

    PubMed 21724699

  • 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.

    PubMed 22108748

  • 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.

    PubMed 30665723

  • 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.

    PubMed 31594647

  • 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.

    PubMed 22468996

  • 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.

    PubMed 39900089

  • 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.

    PubMed 34168032

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing "ACHIM" as solute (10^9 intestinal microbes/ml) in people with Systemic Sclerosis, run by Oslo University Hospital at 4 sites in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

• 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04300426, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in