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. 2024 Dec 22;14(12):e093120.
doi: 10.1136/bmjopen-2024-093120.

Intestinal M icrobiota Transplant Prior to A llogeneic S tem Cell T ransplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial

Benjamin H Mullish  1   2 , Andrew J Innes  3   4 , Lauren A Roberts  1 , Shian Anim-Burton  5 , Lee Webber  5 , Nicholas A Johnson  6 , Rohma Ghani  1   7 , Pakhshan Farshi  8 , Anjum B Khan  9 , Francesca Kinsella  10 , Panagiotis Kottaridis  11 , Pramila Krishnamurthy  12 , Emma Nicholson  13 , Renuka Palanicawandar  3   4 , Graham Wheeler  6   14 , Frances Davies  7 , Julian R Marchesi  15 , Jiří Pavlů  3   4
Affiliations

Intestinal M icrobiota Transplant Prior to A llogeneic S tem Cell T ransplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial

Benjamin H Mullish et al. BMJ Open. .

Abstract

Introduction: Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.

Methods and analysis: 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).

Ethics and dissemination: This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.

Trial registration numbers: NCT6355583; EudraCT: 2022-003617-10.

Trial registration: ClinicalTrials.gov NCT06355583.

Keywords: Bone marrow transplantation; Leukaemia; Microbiota; Transplant medicine.

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Conflict of interest statement

Competing interests: GW is an employee of and holds share in GSK. All other authors have nothing to report

Figures

Figure 1
Figure 1. Study flow chart participant time line. HSCT, haematopoietic cell transplantation; IMT, intestinal microbiota transplant.
Figure 2
Figure 2. ‘Prehabilitation’ of the gut microbiome in MAST. Dynamics of the gut microbiota conventionally through the peri-HCT period are shown in black (as defined previously6); the red line is our predicted higher starting point and nadir for patients receiving a pre-HCT IMT in the MAST trial. GvHD, graft-versus-host disease; HCT, haematopoietic cell transplantation; IMT, intestinal microbiota transplant; ITU, intensive treatment unit; MAST, Microbiota Transplant Prior to Allogeneic Stem Cell Transplant.
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