PMID- 31151436 OWN - NLM STAT- MEDLINE DCOM- 20191230 LR - 20210109 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 19 IP - 1 DP - 2019 May 31 TI - Autologous stem cell transplantation in refractory Crohn's disease - low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study. PG - 82 LID - 10.1186/s12876-019-0992-2 [doi] LID - 82 AB - BACKGROUND: Intestinal inflammation in Crohn's disease (CD) is caused by mucosal immune system reactivity to luminal antigen and results in debilitating symptoms, reduced quality of life, impaired work productivity and significant health care costs. Not all patients respond to conventional and biologic therapies, with chronic inflammation ensuing. Although surgical resection may be required, disease frequently returns and surgery may not be an option, or may be declined. Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD. The ASTIC trial asked whether HSCT could cure CD. Few patients achieved the primary endpoint of clinical remission for 3 months, off all medication with no evidence of active disease, and there were a high number of adverse events (AEs) and serious adverse events (SAEs), including one patient death. However, beneficial effects were observed in some aspects of disease activity. The ASTIClite trial will investigate these potential benefits and safety using a lower intensity regimen than ASTIC. METHODS: Ninety-nine participants will be recruited from secondary care IBD centres in the UK into a multicentre, randomised controlled trial (RCT, ASTIClite) and an observational follow-up, and randomised to autologous HSCT versus standard care (ratio 2:1). The primary endpoint is treatment success at week 48, defined as mucosal healing without surgery or death. Secondary endpoints relating to efficacy, safety and mechanistic analyses will be evaluated at week 8, 14, 24, 32, 40 and 48. Long-term safety of the low intensity HSCT regimen forms the primary endpoint for the EBMT follow-up study and will be assessed annually for 4-7 years. DISCUSSION: ASTIClite will compare HSCTlite with standard care with respect to safety, efficacy and quality of life, and capture outcomes allowing findings to be generalised to current clinical practice in the UK. It will also provide significant mechanistic insights into the immunological consequences of HSCTlite and its impact on treatment outcomes. The observational follow-up will provide information, which is currently unavailable for this population. TRIAL REGISTRATION: The ASTIClite RCT was registered on 31st October 2017 ( ISRCTN17160440 ) and the EBMT follow-up study on 19th January 2018 ( ISRCTN31981313 ). FAU - Snowden, John A AU - Snowden JA AD - Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK. FAU - Hawkey, Chris AU - Hawkey C AD - Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK. FAU - Hind, Daniel AU - Hind D AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. FAU - Swaby, Lizzie AU - Swaby L AUID- ORCID: 0000-0001-9443-7681 AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. e.a.swaby@sheffield.ac.uk. FAU - Mellor, Katie AU - Mellor K AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. FAU - Emsley, Richard AU - Emsley R AD - Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. FAU - Mandefield, Laura AU - Mandefield L AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. FAU - Lee, Ellen AU - Lee E AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. FAU - Badoglio, Manuela AU - Badoglio M AD - European Society for Blood and Marrow Transplantation, Paris, France. FAU - Polge, Emmanuelle AU - Polge E AD - European Society for Blood and Marrow Transplantation, Paris, France. FAU - Labopin, Myriam AU - Labopin M AD - European Society for Blood and Marrow Transplantation, Paris, France. FAU - Gribben, John AU - Gribben J AD - Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK. FAU - Pockley, A Graham AU - Pockley AG AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. FAU - Foulds, Gemma A AU - Foulds GA AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. FAU - Lobo, Alan AU - Lobo A AD - Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK. FAU - Travis, Simon AU - Travis S AD - Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK. FAU - Parkes, Miles AU - Parkes M AD - Department of Medicine, University of Cambridge, Cambridge, UK. FAU - Satsangi, Jack AU - Satsangi J AD - Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK. FAU - Papaioannou, Diana AU - Papaioannou D AD - Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. FAU - Lindsay, James O AU - Lindsay JO AD - Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK. CN - Autologous Stem Cell Transplantation In Refractory CD - Low Intensity Therapy Evaluation Study Investigators CN - European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) LA - eng GR - EME/15/178/09/DH_/Department of Health/United Kingdom GR - 15/178/09/Efficacy and Mechanism Evaluation Programme/ PT - Clinical Trial Protocol PT - Journal Article PT - Multicenter Study DEP - 20190531 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 SB - IM MH - Adolescent MH - Adult MH - Crohn Disease/*therapy MH - Female MH - Follow-Up Studies MH - Hematopoietic Stem Cell Transplantation/*methods MH - Humans MH - Male MH - Middle Aged MH - Observational Studies as Topic MH - Randomized Controlled Trials as Topic MH - Transplantation, Autologous MH - Treatment Outcome MH - Young Adult PMC - PMC6544952 OTO - NOTNLM OT - Autologous stem cell transplant OT - Crohn's disease OT - Observational study OT - Randomised controlled trial COIS- JAS declares financial support for speaking at educational events supported by Janssen, Jazz Pharma, Mallinckrodt, is a member of a trial IDMC for Kiadis Pharma. No other competing interests were declared by named authors. FIR - Whitby, Liam IR - Whitby L FIR - Mahida, Yash IR - Mahida Y FIR - Moran, Gordon IR - Moran G FIR - Subramanian, Sree IR - Subramanian S FIR - Irving, Peter IR - Irving P FIR - Din, Shahida IR - Din S FIR - Byrne, Jenny IR - Byrne J FIR - Uttenthal, Ben IR - Uttenthal B FIR - Patel, Amit IR - Patel A FIR - Johnson, Peter IR - Johnson P FIR - Kazmi, Majid IR - Kazmi M FIR - Peniket, Andy IR - Peniket A FIR - Rutella, Sergio IR - Rutella S FIR - Bradburn, Mike IR - Bradburn M FIR - Loban, Amanda IR - Loban A EDAT- 2019/06/04 06:00 MHDA- 2019/12/31 06:00 PMCR- 2019/05/31 CRDT- 2019/06/02 06:00 PHST- 2019/04/12 00:00 [received] PHST- 2019/05/01 00:00 [accepted] PHST- 2019/06/02 06:00 [entrez] PHST- 2019/06/04 06:00 [pubmed] PHST- 2019/12/31 06:00 [medline] PHST- 2019/05/31 00:00 [pmc-release] AID - 10.1186/s12876-019-0992-2 [pii] AID - 992 [pii] AID - 10.1186/s12876-019-0992-2 [doi] PST - epublish SO - BMC Gastroenterol. 2019 May 31;19(1):82. doi: 10.1186/s12876-019-0992-2.