Clostridioides Difficile: Understanding Responses and Treatment Effects (CURE-CDI)

Studies of Treatment Effects, Host-Pathogen Responses, and Therapeutic Mechanisms in Clostridioides Difficile Infection

The goal of this observational study is to learn how different treatments for Clostridioides difficile infection (CDI) work, and which biological mechanisms are involved in recovery. The study will compare standard antibiotic treatment and fecal microbiota transplantation (FMT).

The main questions it aims to answer are:

• How do antibiotic treatment and FMT affect treatment outcome in CDI?
• How does the gut microbiota change during and after treatment?
• Which microbial and metabolic factors are associated with recovery or treatment failure?
• How does treatment affect the intestinal barrier, immune response, and patient-reported quality of life?

Participants with CDI will receive treatment as part of routine clinical care, either antibiotics or FMT. Researchers will follow participants over time and collect biological samples to study treatment effects.

Participants will:

• Provide stool samples during the acute infection and during follow-up
• Have treatment outcomes assessed at 2 and 8 weeks
• Be followed for up to 5 years to study long-term effects
• Provide blood and urine samples during follow-up
• Provide nasal samples to study potential microbiota changes at distant body sites
• Complete questionnaires on symptoms and health-related quality of life
• In a subgroup, undergo repeated sigmoid biopsies to study intestinal mucosal healing

The results are expected to increase understanding of how FMT and antibiotics lead to recovery in CDI and may support improved and more targeted future treatments.

Study Overview

• Status: Recruiting
• Conditions: Clostridioides Difficile Infection
• Intervention / Treatment: Other: Antibiotic treatment; Other: Fecal microbiota transplantation (FMT)

Detailed Description

Clostridioides difficile infection (CDI) is a frequent cause of antibiotic-associated colitis and is characterized by high rates of recurrence and, in some patients, refractory disease. Although fecal microbiota transplantation (FMT) is an effective treatment for recurrent and refractory CDI, the biological mechanisms underlying treatment response, early clinical improvement, long-term effects, and vulnerability to subsequent antibiotic exposure remain incompletely understood.

This is an observational study designed to characterize biological and clinical changes associated with standard antibiotic treatment and FMT in patients with CDI. The study will investigate intestinal microbiota composition, microbial metabolites, mucosal and systemic immune responses, intestinal barrier function, and patient-reported outcomes, and relate these findings to clinical disease course and treatment outcome.

Adult patients with symptomatic, microbiologically verified CDI receiving routine clinical care will be included. Treatment decisions, including the use of antibiotics or FMT, are made by the treating physician according to clinical guidelines and are not influenced by study participation. Participants will be followed longitudinally for up to five years.

Biological samples will be collected during the acute CDI episode and at predefined follow-up time points. Stool samples will be obtained to characterize intestinal microbiota composition and metabolic profiles over time. In participants treated with FMT, stool sampling will be more frequent during the first week after treatment to capture early post-treatment changes. Blood samples will be collected for assessment of systemic immune and inflammatory markers. Urine samples will be collected for analysis of metabolites related to intestinal barrier integrity. Nasopharyngeal swabs will be obtained to explore whether modulation of the intestinal microbiota is associated with changes in microbiota composition and immune responses at distant mucosal sites.

In a subgroup of participants deemed suitable by the responsible clinician, repeated lower colonic biopsies will be obtained using sigmoidoscopy. These samples will be used to assess colonic mucosal healing, mucus barrier function, mucosa-associated microbiota, and local immune responses.

Microbiota analyses will include metagenomic sequencing approaches, and metabolomic analyses will be performed on stool and other biological samples. Immune responses will be assessed using biochemical and cellular assays in blood, mucosal tissue, and relevant sample types. Donor fecal material used for FMT will be analyzed and related to recipient outcomes.

Clinical outcomes will be assessed at 2 and 8 weeks after initiation of the current CDI treatment and during long-term follow-up. Disease severity and treatment outcomes, including treatment response, recurrence, refractory disease, and sustained cure, will be classified according to established clinical guidelines. Participants experiencing treatment failure may re-enter sampling schedules corresponding to subsequent treatment courses.

Patient-reported health-related quality of life will be assessed during acute infection and follow-up using validated generic and disease-specific instruments.

This study aims to provide a detailed characterization of biological and clinical processes associated with FMT and antibiotic treatment in CDI, including early and long-term effects, and to support future optimization of microbiota-based therapeutic strategies.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Johan Rasmuson, MD, PhD; Phone Number: 0046-907850000; Email: johan.rasmuson@umu.se

Study Locations

• Sweden
  • Umeå, Sweden
    • Recruiting
    • Umea University Hospital
    • Contact: Johan Rasmuson, MD, PhD; Phone Number: 0046-907850000; Email: johan.rasmuson@umu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with symptomatic, microbiologically verified Clostridioides difficile infection receiving inpatient or outpatient care at Umeå University Hospital.

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Symptomatic, microbiologically verified Clostridioides difficile infection
• Receiving inpatient or outpatient care at Umeå University Hospital
• Able and willing to provide written informed consent
• Willing to participate in protocol-driven follow-up for up to 5 years

Exclusion Criteria:

• Age below 18 years
• Inability to provide written informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Antibiotic treatment; Participants with Clostridioides difficile infection receiving standard antibiotic treatment as part of routine clinical care.	Other: Antibiotic treatment; Standard antibiotic treatment for Clostridioides difficile infection administered as part of routine clinical care, according to clinical guidelines. Treatment selection and duration are determined by the treating physician.
Fecal microbiota transplantation (FMT); Participants with Clostridioides difficile infection receiving fecal microbiota transplantation as part of routine clinical care.	Other: Fecal microbiota transplantation (FMT); Fecal microbiota transplantation administered as part of routine clinical care for Clostridioides difficile infection. The route of administration is determined by clinical practice and physician decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with sustained cure	Number of participants with sustained cure, defined as resolution of Clostridioides difficile infection symptoms after completion of the current treatment course and no recurrence during the 8-week follow-up period.	At follow-up 8 weeks after initiation of the current CDI treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with CDI recurrence	Number of participants with Clostridioides difficile infection recurrence during the 8-week follow-up period, classified according to established clinical guidelines.	At follow-up 8 weeks after initiation of the current CDI treatment
Intestinal microbiota diversity	Changes in intestinal microbiota diversity assessed by metagenomic sequencing of stool samples.	Baseline and longitudinal follow-up up to 5 years
Stool short-chain fatty acid concentrations	Changes in stool short-chain fatty acid concentrations assessed using metabolomic methods.	Baseline and longitudinal follow-up up to 5 years
Colonic mucus barrier function	Changes in colonic mucus barrier function assessed by ex vivo measurements of mucus growth rate and mucus layer integrity in colonic biopsy samples obtained from a subgroup of participants.	Baseline and follow-up assessments up to approximately 8 weeks after initiation of the current CDI treatment
Circulating markers of intestinal barrier function	Changes in circulating biomarkers related to intestinal barrier function measured in peripheral blood.	Baseline and longitudinal follow-up up to 5 years
Health-related quality of life	Patient-reported health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) health index value (higher values indicate better quality of life).	Baseline and longitudinal follow-up up to 5 years
Health-related quality of life	Patient-reported health-related quality of life assessed using the Clostridioides difficile Quality of Life Survey (Cdiff32) total score (range 0-100; higher scores indicate better quality of life).	Baseline and longitudinal follow-up up to 5 years
Number of participants with new Clostridioides difficile infection episodes after subsequent antibiotic exposure	Occurrence of new Clostridioides difficile infection episodes following exposure to non-CDI antibiotic treatment during follow-up.	From 8 weeks after initiation of the current CDI treatment and up to 5 years

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Region Västerbotten
• Investigators: Principal Investigator: Johan Rasmuson, MD, PhD, Umeå University, Department of Clinical Microbiology and Umeå University Hospital, Department of Infectious Diseases

Study record dates

Study Major Dates

• Study Start (Estimated): January 26, 2026
• Primary Completion (Estimated): December 1, 2040
• Study Completion (Estimated): December 1, 2045

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Gut microbiota; Observational study; Immune response; Microbial metabolites; Intestinal barrier; Dysbiosis; Antibiotic treatment; Fecal microbiota transplantation; Clostridioides difficile infection; Microbiome engraftment; Recurrent Clostridioides difficile infection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Dysbiosis; Clostridium Infections; Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: CURE-CDI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to the sensitive nature of the clinical and biological data collected in this observational study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No