Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study

Oct 9, 2024BMJ open

Semaglutide treatment to prevent side effects during high-dose chemotherapy with stem cell transplant: study plan for a controlled clinical trial

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Abstract

Forty adult patients with malignant lymphoma will be randomized to receive either semaglutide or placebo over 8 weeks.

The study investigates the effect of the semaglutide on severity in patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
Endogenous GLP-1 levels may correlate with reduced toxicities following hematopoietic stem cell transplantation.
In previous mouse studies, GLP-1 receptor agonists have shown potential to limit chemotherapy-induced mucositis.
The primary endpoint is the mean GI mucositis severity grade during the first four weeks after auto-HSCT.
Secondary endpoints include changes in C-reactive protein, quality of life, and various safety measures.

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INTRODUCTION: Cancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is no effective prophylaxis against this. Glucagon-like peptide 1 (GLP-1), a well-known regulator of blood glucose, has been suggested in mouse studies to possess trophic effects on gut epithelial cells as well as anti-inflammatory properties. In line with this, endogenous GLP-1 levels have been shown to be inversely correlated with toxicities after haematopoietic stem cell transplantation (HSCT) and treatment with a (GLP-1RA) was shown to limit chemotherapy-induced mucositis in rodents. This present study investigates the effects of the GLP-1RA semaglutide on GI mucositis severity score in patients with lymphoma undergoing high-dose chemotherapy followed by autologous (auto) HSCT.

METHODS AND ANALYSIS: This is a randomised, double-blind, placebo-controlled, two-centre investigator-initiated clinical study. Forty adult patients with malignant lymphoma referred for auto-HSCT will be randomised in a 1:1 manner to receive either semaglutide or placebo once-weekly for 8 weeks. This includes a run-in period of 3-4 weeks with semaglutide 0.25 mg prior to high-dose chemotherapy treatment followed by a period of 4-5 weeks with semaglutide 0.5 mg including the 1 week of high-dose chemotherapy treatment. Clinical assessment of endpoint measurements and safety will be performed weekly during treatment and in a follow-up period of 10 weeks. The primary endpoint is GI mucositis severity (mean severity grade (0-II) during week 1-4 after auto-HSCT). Secondary endpoints include C-reactive protein increment, quality of life and safety. Fever, bacteraemia, antibiotic use, weight loss, morphine consumption, duration of hospitalisation, use of parenteral nutrition, change in muscle mass and clinical and laboratory evidence of organ toxicities will also be assessed.

ETHICS AND DISSEMINATION: The study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Danish National Medical Research Ethics Committee (EU CT #2022-502139-20-00) and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark's good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and international scientific meetings and in peer-reviewed scientific journals.

TRIAL REGISTRATION NUMBER: NCT06449625.

Key numbers

Participants

Total number of patients to be randomized in the study.

8 weeks

Dosage Duration

Duration of treatment with semaglutide or placebo.

20–22 weeks

Study Timeline

Total duration of study participation for each patient, including screening and follow-up.

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Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study

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