The goal of this clinical trial is to determine the outcome of patients with immune checkpoint inhibitor-mediated diarrhea/colitis (IMC) treated with faecal microbiota transplantation (FMT) in a randomised, placebo-controlled trial. The aim of the present study is to assess the feasibility, pilot efficacy, and safety of FMT for patients with IMC. Participants will be treated two times with capsule FMT or placebo capsules in a 1:1 ratio. The intervention treatment will be an add-on to the patients' standard treatment for IMC. Researchers will compare the FMT-treated group to the placebo-treated group to see if FMT promotes remission of IMC.
As above
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
20
Capsule FMT
Placebo capsules
Aarhus University Hospital
Aarhus N, Denmark
RECRUITINGClinical remission of immune-mediated diarrhea
Number of patients with steroid-free resolution of diarrhea, defined as \< 3 liquid stools (Bristol \<6) per 24 hours during day 40 and 41 after the last intervention treatment.
Time frame: At 42 days after intervention treatment
Remission of diarrhea defined by CTCAE
Number of patients in steroid-free clinical remission of diarrhea 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as \< 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), at day 40 and 41.
Time frame: At 42 days after intervention treatment
Remission of colitis defined by CTCAE
Number of patients in steroid-free clinical remission of colitis 6 weeks (42 days) after the last intervention treatment. Clinical remission is defined as asymptomatic in regards to colitis (CTCAE colitis grade 1 or less), at day 40 and 41.
Time frame: At 42 days after intervention treatment
Therapy response of FMT
Therapy response defined as a decrease of at least 3 points in Simple Clinical Colitis Activity Index (SCCAI) score, at weeks 1, 6 and 12 after the last intervention treatment.
Time frame: Up to 12 weeks after intervention treatment
Number of days until CTCAE diarrhea grade 1
Number of days until less than 4 stools over baseline per day (CTCAE diarrhea grade 1 or less), lasting a minimum of 48 consecutive hours with no increase in steroid dose in the 12 weeks of follow-up.
Time frame: Up to 12 weeks after intervention treatment
Number of days until resolution of diarrhea
Number of days until resolution of diarrhea, defined as 3 or fewer Bristol type 6-7 stools per day, lasting a minimum of 48 consecutive hours.
Time frame: Up to 12 weeks after intervention treatment
Incidence of fecal microbiota transplantation (FMT)-related adverse events
Number of adverse events (AE) during first 6 weeks after intervention treatment. AE's will be graded by CTCAE.
Time frame: At 42 days after intervention treatment
Incidence of fecal microbiota transplantation (FMT)-related serious adverse events
Number of serious adverse events (SAE) during 12 weeks follow-up after the final intervention treatment. SAE's will be graded by CTCAE.
Time frame: At 12 weeks after intervention treatment
Faecal microbiota composition
Changes in faecal microbiome composition from baseline to week 6 after the last intervention.
Time frame: Up to 6 weeks after intervention treatment
Gut mucosa-associated microbiome
Changes in mucosa-associated microbiome from baseline to week 6 after the last intervention.
Time frame: Up to 6 weeks after intervention treatment
Faecal-calprotectin
Percentual change in faecal-calprotectin from prior to intervention to week 6 after the last intervention.
Time frame: Up to 6 weeks after intervention treatment
Blood immunological parameters
Changes in blood immunological parameters (including circulating cytokines) from baseline and at week 6 after the last intervention.
Time frame: Up to 6 weeks after intervention treatment
Hospitalisation
Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up.
Time frame: Up to 12 weeks after intervention treatment
Colectomy
Colectomy during 12 weeks of follow-up.
Time frame: Up to 12 weeks after intervention treatment
Mortality
Mortality during the 12 weeks of follow-up.
Time frame: Up to 12 weeks after intervention treatment
Accumulated steroid dose
Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment.
Time frame: Up to 12 weeks after intervention treatment
Resumption of immune checkpoint inhibitor therapy
Number of patients resuming immune checkpoint inhibitor therapy during the 12 weeks of follow-up.
Time frame: Up to 12 weeks after intervention treatment
Response to immune checkpoint inhibitor therapy
Response to immune checkpoint inhibitor therapy defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1 and iRECIST).
Time frame: Up to 12 weeks after intervention treatment
Patient and physician perceptions of FMT treatment
Patient and physician perceptions of FMT treatment and the usage for IMC assessed by a patient questionnaire at week 6 and a physician questionnaire.
Time frame: At 42 days after intervention treatment
Health-related quality of life
Changes in health-related quality of life assessed by EQ-5D-5L at baseline and week 6.
Time frame: At 42 days after intervention treatment
Endoscopic response
Endoscopic response, defined as decrease in Mayo endoscopic score ≥1 grade, at week 6 after the last intervention treatment.
Time frame: Up to 6 weeks after intervention treatment
Endoscopic remission
Endoscopic remission, defined as Mayo endoscopic score 0, at week 6 after the last intervention treatment.
Time frame: Up to 6 weeks after intervention treatment
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