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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Faecal microbiota transplantation (FMT) | Experimental | Patients receive two applications of capsule FMT with 3-7 days between applications. |
|
| Placebo | Placebo Comparator | Patients receive two applications of placebo capsules with 3-7 days between applications. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Faecal Microbiota Transplantation (FMT) | Procedure | Capsule FMT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical 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. | At 42 days after intervention treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 42 days after intervention treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Trine L Laursen, BSc | Contact | +4540408207 | trnlau@rm.dk | |
| Christian L Hvas, PhD | Contact | +4528351839 | christian.hvas@auh.rm.dk |
| Name | Affiliation | Role |
|---|---|---|
| Christian L Hvas, PhD | University of Aarhus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Recruiting | Aarhus N | 8200 | Denmark |
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| Label | URL |
|---|---|
| Centre for faecal microbiota transplantation (CEFTA) | View source |
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Open access publication, raw data available upon reasonable request and according to data protection regulation.
Protocol: On request. Other: after study completion
Evaluated after email request, trnlau@rm.dk
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| D003092 | Colitis |
| D008545 | Melanoma |
| D007680 | Kidney Neoplasms |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005759 | Gastroenteritis |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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This is a double-blind, placebo controlled, randomised trial
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| Placebo | Procedure | Placebo capsules |
|
| 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. |
| 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. | 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. | 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. | 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. | 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. | At 12 weeks after intervention treatment |
| Faecal microbiota composition | Changes in faecal microbiome composition from baseline to week 6 after the last intervention. | 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. | 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. | 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. | Up to 6 weeks after intervention treatment |
| Hospitalisation | Hospitalisation defined as the total number of days hospitalised, during 12 weeks of follow-up. | Up to 12 weeks after intervention treatment |
| Colectomy | Colectomy during 12 weeks of follow-up. | Up to 12 weeks after intervention treatment |
| Mortality | Mortality during the 12 weeks of follow-up. | Up to 12 weeks after intervention treatment |
| Accumulated steroid dose | Accumulated steroid dose (total dose in mg) during 12 weeks following experimental treatment. | 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. | 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). | 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. | 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. | 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. | 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. | Up to 6 weeks after intervention treatment |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |