Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial
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 prolong...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-12-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/12/e093120.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841550995069337600 |
|---|---|
| author | Julian R Marchesi Emma Nicholson Benjamin H Mullish Renuka Palanicawandar Graham Wheeler Francesca Kinsella Andrew J Innes Lauren A Roberts Shian Anim-Burton Lee Webber Nicholas A Johnson Rohma Ghani Pakhshan Farshi Anjum B Khan Panagiotis Kottaridis Pramila Krishnamurthy Frances Davies Jiří Pavlů |
| author_facet | Julian R Marchesi Emma Nicholson Benjamin H Mullish Renuka Palanicawandar Graham Wheeler Francesca Kinsella Andrew J Innes Lauren A Roberts Shian Anim-Burton Lee Webber Nicholas A Johnson Rohma Ghani Pakhshan Farshi Anjum B Khan Panagiotis Kottaridis Pramila Krishnamurthy Frances Davies Jiří Pavlů |
| author_sort | Julian R Marchesi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-71a49a9381f6428f8f63bf3a532566a2 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-71a49a9381f6428f8f63bf3a532566a22025-01-09T17:15:10ZengBMJ Publishing GroupBMJ Open2044-60552024-12-01141210.1136/bmjopen-2024-093120Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trialJulian R Marchesi0Emma Nicholson1Benjamin H Mullish2Renuka Palanicawandar3Graham Wheeler4Francesca Kinsella5Andrew J Innes6Lauren A Roberts7Shian Anim-Burton8Lee Webber9Nicholas A Johnson10Rohma Ghani11Pakhshan Farshi12Anjum B Khan13Panagiotis Kottaridis14Pramila Krishnamurthy15Frances Davies16Jiří Pavlů17Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UKDepartment of Haematology, The Royal Marsden Hospital, London, UKDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UKCentre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UKImperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UKDepartment of Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKCentre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UKDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UKCancer Research UK Imperial Centre, Clinical Trials Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKCancer Research UK Imperial Centre, Clinical Trials Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKImperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UKDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UKDepartment of Haematology, Manchester Royal Infirmary, Manchester, UKDepartment of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UKDepartment of Haematology, University College London Hospitals NHS Foundation Trust, London, UKDepartment of Haematology, King`s College Hospital NHS Foundation Trust, London, UKDepartment of Infectious Diseases, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UKCentre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UKIntroduction 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.https://bmjopen.bmj.com/content/14/12/e093120.full |
| spellingShingle | Julian R Marchesi Emma Nicholson Benjamin H Mullish Renuka Palanicawandar Graham Wheeler Francesca Kinsella Andrew J Innes Lauren A Roberts Shian Anim-Burton Lee Webber Nicholas A Johnson Rohma Ghani Pakhshan Farshi Anjum B Khan Panagiotis Kottaridis Pramila Krishnamurthy Frances Davies Jiří Pavlů Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial BMJ Open |
| title | Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial |
| title_full | Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial |
| title_fullStr | Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial |
| title_full_unstemmed | Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial |
| title_short | Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial |
| title_sort | intestinal microbiota transplant prior to allogeneic stem cell transplant mast trial study protocol for a multicentre double blinded placebo controlled phase iia trial |
| url | https://bmjopen.bmj.com/content/14/12/e093120.full |
| work_keys_str_mv | AT julianrmarchesi intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT emmanicholson intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT benjaminhmullish intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT renukapalanicawandar intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT grahamwheeler intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT francescakinsella intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT andrewjinnes intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT laurenaroberts intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT shiananimburton intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT leewebber intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT nicholasajohnson intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT rohmaghani intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT pakhshanfarshi intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT anjumbkhan intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT panagiotiskottaridis intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT pramilakrishnamurthy intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT francesdavies intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial AT jiripavlu intestinalmicrobiotatransplantpriortoallogeneicstemcelltransplantmasttrialstudyprotocolforamulticentredoubleblindedplacebocontrolledphaseiiatrial |