Microbiota Restoration Therapy for Recurrent Clostridium Difficile-associated Diarrhea

Overview

About this study

This study will assess the safety of a new biologic drug, RBX2660 (microbiota suspension) as a treatment for recurrent Clostridium difficile-associated diarrhea (CDAD), which is the primary symptom of recurrent Clostridium difficile infection. All eligible subjects will receive RBX2660.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

≥ 18 years
Medical record documentation of CDAD either:
1. at least two recurrences after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or
2. have had at least two episodes of severe CDAD resulting in hospitalization.
Willing and able to have an enema(s).
Already taking or will start a course of oral antibiotics for CDAD symptoms for 10-14 days, including at least seven days of oral vancomycin.
Willing and able to complete the required subject diary.

Exclusion Criteria:

Continued (uncontrolled) CDAD after completing a 10-14 day course of oral antibiotics.
Requires antibiotic therapy for a condition other than CDAD.
Previous fecal transplant prior to study enrollment.
History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
History of irritable bowel syndrome (IBS).
History of chronic diarrhea.
History of celiac disease.
History of cirrhosis of the liver or ascites.
Disease symptoms caused by a confirmed intestinal pathogen other than Clostridium difficile.
Has a colostomy.
Intraabdominal surgery within the last 60 days.
Evidence of active, severe colitis.
History of short gut syndrome or motility disorders.
Requires the regular use of medications that affect bowel motility (e.g., metoclopramide, narcotics, loperamide).
Planned therapy in the next 3 months that may cause diarrhea (e.g., chemotherapy).
Planned surgery requiring perioperative antibiotics within 6 months of study enrollment.
Life expectancy of < 12 months.
Compromised immune system, e.g., HIV infection (any CD4 count); AIDS-defining diagnosis or CD4 <200/mm3; inherited/primary immune disorders; immunodeficient or immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy; or current or recent (< 90 days) treatment with immunosuppressant medications.
Taking steroids (≥ 20 mg a day) or is expected to be on steroids for more than 30 days after enrollment.
Neutropenia (white blood cell count <1000 cells/µL).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status
Scottsdale/Phoenix, Ariz. Mayo Clinic principal investigator Robert Orenstein, D.O.	Closed for enrollment

Mayo Clinic Location

Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Robert Orenstein, D.O.

Closed for enrollment

More information

Publications

Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. Read More on PubMed
Clostridium difficile infection rates are Climbing in frequency and severity, and the spectrum of susceptible patients is expanding beyond the traditional scope of hospitalized patients receiving antibiotics. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of > 90% are being consistently reported from multiple centers. Transplantation can be provided through a variety of methodologies, either to the lower proximal, lower distal, or upper gastrointestinal tract. This review summarizes reported results, factors in donor selection, appropriate patient criteria, and the various preparations and mechanisms of fecal microbiota transplant delivery available to clinicians and patients. Read More on PubMed
Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices. Read More on PubMed

Clinical Trials