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

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Snowden, JA, Hawkey, C, Hind, D, Swaby, L, Mellor, K, Emsley, R, Mandefield, L, Lee, E, Badoglio, M, Polge, E, Labopin, M, Gribben, J, Pockley, AG ORCID: https://orcid.org/0000-0001-9593-6431, Foulds, GA ORCID: https://orcid.org/0000-0002-2053-7580, Lobo, A, Travis, S, Parkes, M, Satsangi, J, Papaioannou, D and Lindsay, JO, 2019. 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. BMC Gastroenterology, 19 (1): 82. ISSN 1471-230X

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Official URL: https://doi.org/10.1186/s12876-019-0992-2

Abstract

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 ).

Item Type:	Journal article
Publication Title:	BMC Gastroenterology
Creators:	Snowden, J.A., Hawkey, C., Hind, D., Swaby, L., Mellor, K., Emsley, R., Mandefield, L., Lee, E., Badoglio, M., Polge, E., Labopin, M., Gribben, J., Pockley, A.G., Foulds, G.A., Lobo, A., Travis, S., Parkes, M., Satsangi, J., Papaioannou, D. and Lindsay, J.O.
Publisher:	BioMed Central
Date:	December 2019
Volume:	19
Number:	1
ISSN:	1471-230X
Identifiers:	Number Type 10.1186/s12876-019-0992-2 DOI 1215904 Other
Rights:	Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	11 Nov 2019 12:12
Last Modified:	11 Nov 2019 12:12
URI:	https://irep.ntu.ac.uk/id/eprint/38200