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

Study Overview
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Brief Summary
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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.

Detailed Description
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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)

Official Title
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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

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Other: Serum-derived bovine immunoglobulin/protein isolate (SBI)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI, C. diff, Ulcerative Colitis, UC, IBD, Inflammatory Bowel Disease