To Evaluate the Impact of SBI on C. Difficile in Hospitalized UC Patients

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Impact of Serum-derived Bovine Immunoglobulin/Protein Isolate (SBI) on Clostridium Difficile (C. Difficile) Infection (CDI) in Hospitalized Ulcerative Colitis (UC) Patients

The effects of serum-derived bovine immunoglobulin/protein isolate (SBI) will be evaluated and compared to matching placebo in two distinct patient populations:

I. Hospitalized ulcerative colitis (UC) patients who tested positive for Clostridium difficile (C. difficile) at time of admission and are receiving vancomycin.

II. Hospitalized UC patients who tested negative for C. difficile at time of admission.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile
• Intervention / Treatment: Other: Placebo; Other: Serum-derived bovine immunoglobulin/protein isolate (SBI)

Detailed Description

The effects of serum-derived bovine immunoglobulin/protein isolate (SBI) will be evaluated and compared to matching placebo in two distinct patient populations:

I. Hospitalized ulcerative colitis (UC) patients who tested positive for Clostridium difficile (C. difficile) at time of admission and are receiving vancomycin.

Primary Objective:

• To evaluate the effect of SBI on time (# of days) to resolution of diarrhea, defined as a consecutive 24 hour period with only formed bowel movements (Bristol Stool Scale (BSS) ≤ 4) in this patient population

Secondary Objectives:

• To evaluate the ability of SBI to decrease the incidence of recurrent C. difficile infection (CDI) following successful treatment with vancomycin.
• To evaluate the effect of SBI on UC status
• To evaluate the effect of SBI on nutritional status
• To evaluate the safety and tolerability of SBI
• To evaluate the effect of SBI on subjects' quality of life (QOL)
• To investigate the effect of SBI in fecal microbiome
• To evaluate the length of hospitalization (time of hospitalization to time of discharge)

II. Hospitalized UC patients who tested negative for C. difficile at time of admission.

Primary Objective:

• To evaluate the effect of SBI on time (# of days) to resolution of diarrhea, defined as a consecutive 24 hour period with only formed bowel movements (Bristol Stool Scale (BSS) ≤ 4) in this patient population

Secondary Objectives:

• To evaluate the effect of SBI in decreasing the incidence of CDI
• To evaluate the effect of SBI on UC status
• To evaluate the effect of SBI on nutritional status
• To evaluate the safety and tolerability of SBI
• To evaluate the effect of SBI on subjects' QOL
• To investigate the effect of SBI in fecal microbiome
• To evaluate the length of hospitalization (time of hospitalization to time of discharge)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60657
      • Rush University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of UC confirmed by colonoscopy and histology.
• Confirmed active UC upon hospital admission, defined by a partial Mayo Score of ≥ 3 with a stool frequency subscore of ≥ 2.
• Concomitant therapy for UC will be permitted. Subjects will be instructed not to make any medication changes after hospital discharge before first discussing with the Investigator.
• Eligible subjects will be assigned to one of two different and independent patient groups based on C. difficile status as determined by clinical symptoms with diarrhea and laboratory tests: either a polymerase chain reaction (PCR) assay or glutamate dehydrogenase (GDH) screening test used in two- or three-step algorithm with subsequent toxin A and B EIA testing.

Exclusion Criteria:

• Subjects with history of constipation within a week of the screening visit; or any serious hepatic, renal, cardiovascular, neurological or hematological disorder in the opinion of the Investigator.
• Subjects with history of drug or alcohol abuse, history of psychiatric disorders, known allergy or hypersensitivity to beef or any component of SBI.
• Subjects with a history of antibiotic treatment within the 4 weeks prior to enrollment.

• Subjects using anti-diarrheal medications (e.g., loperamide and bismuth subsalicylate).

  • Note: anti-diarrheal medications will be prohibited throughout the study.
• Subjects who have been admitted to the hospital more than 48 hours prior to enrollment.
• Women who are pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo BID; Placebo	Other: Placebo
Active Comparator: SBI 10 g BID; Serum-derived bovine immunoglobulin/protein isolate (SBI) 10.0 grams twice per day	Other: Serum-derived bovine immunoglobulin/protein isolate (SBI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (# of days) to resolution of diarrhea	Group 1 & Group 2 subjects: Stool consistency will be assessed using the BSS. Subjects will be provided a daily diary A to record the time and consistency of each bowel movement in a 24 hour period. At the Week 4 visit, the Investigator will calculate the time (# of days) to resolution of diarrhea, defined as a consecutive 24 hour period with only formed bowel movements (BSS ≤ 4), after initiation of investigational product (Day 1).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of recurrent CDI	Group I subjects: if subject develops diarrhea (≥ 3 unformed stools in 24h period) at any point following successful treatment with vancomycin. The presence of C. difficile will be determined by PCR or GDH/Toxin EIA.	12 weeks
Incidence of C. difficile	Group II subjects: Incidence of C. difficile will be determined following 12 weeks of investigational product. Symptoms will be assessed by daily diary and by P SCCAI at each study visit. Should the subject develop diarrhea (≥ 3 unformed stools in 24h period) at any point during the study participation, he/she will return to the clinic and be tested for C. difficile by PCR or GDH/Toxin EIA.	12 weeks
UC status measured by P-SCCAI	Group I & Group II subjects	4, 8 and 12 weeks
UC status measured by BSS	Group I & Group II subjects	4 weeks
UC status measured by Fecal calprotectin	Group I & Group II subjects	12 weeks
UC status measured by CRP	Group I & Group II subjects	12 weeks
UC status measured by colectomy rate	Group I & Group II subjects	12 weeks
Nutritional Status measured by pre-albumin	Group I & Group II subjects	12 weeks
Nutritional Status measured by albumin	Group I & Group II subjects	12 weeks
Nutritional Status measured by hand grip strength	Group I & Group II subjects	12 weeks
Nutritional Status measured by fecal alpha-1 antitrypsin	Group I & Group II subjects	12 weeks
Safety and Tolerability evaluated by reported and observed treatment related adverse events	Group I & Group II subjects	12 weeks
Quality of Life evaluated using the SF-36	Group I & Group II subjects	12 weeks
Fecal Microbiome	Group I & Group II subjects	12 weeks
Length of Hospitalization	Group I & Group II subjects	12 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Entera Health, Inc
• Investigators: Principal Investigator: Stephen B Hanauer, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 12, 2017
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimate): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Inflammatory Bowel Disease; IBD; CDI; UC; C. diff
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: STU00200335