A Prospective, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study of Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis and Its Effects on Mucosal Immune State and Microbiota
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Colitis, Ulcerative
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 16
- Locations
- 17
- Primary Endpoint
- Percentage of Participants Who Achieved a Clinical Response at Week 12
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of trichuris suis ova (TSO) in ulcerative colitis (UC). We will look at how TSO affects the body's immune response and if there are related changes in participants' UC.
Detailed Description
The cause of UC, an inflammatory bowel disease (IBD), is not well understood. It is believed to be caused from an abnormal immune response to the normal bacteria that live in the gut (intestines and colon). This response acts as an "attack" on the healthy tissue of the bowel by a person's own immune cells which leads to disease. It is well known that autoimmune diseases such as IBD, asthma, diabetes, and multiple sclerosis are more common in industrialized, well-developed countries with better sanitation and hygiene, as in the United States. These "cleaner" environments reduce exposure to germs and parasites naturally found in the environment. This reduced exposure may trigger responses in the body that make people more prone to diseases such as UC. People in non-industrialized countries and the tropics, where parasites are common, rarely develop these diseases. This observation has led researchers to want to better understand the relationship between the lack of natural bacteria in the gut and the onset of autoimmune diseases like as UC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject has provided written informed consent
- •Diagnosis of UC (newly diagnosed or established patients) as determined by medical history, endoscopic and histological confirmation with the proximal disease extent limited to the left colon (distal to the splenic flexure), and accessible by flexible sigmoidoscopy. Patients with left-sided disease and the presence of a periappendiceal red patch (limited cecal inflammation) will be eligible as long as there is no intervening evidence of colitis between the cecal base and the upper boundary of inflammation in the left colon.
- •Mayo score \>/= 4, as scored at Screen 2
- •If taking the following medications at Screen 1, subjects must meet the following criteria:
- •Oral Corticosteroids: stable treatment for at least 4 weeks prior to Day 0 with a maximum dose equivalent to \<\\=15 mg/day of prednisone
- •Immunosuppressants (azathioprine (AZA) or 6-mercaptopurine (6-MP)): treatment for at least 12 weeks with a stable dose, not exceeding 2.5 mg/kg/day of AZA or 1.5 mg/kg/day of 6-MP, during the 4 weeks prior to Day 0
- •Aminosalicylates: stable oral doses up to 4.8 g/day for at least 4 weeks prior to Day 0.
Exclusion Criteria
- •Subjects whose UC is anticipated to require surgical, endoscopic, or radiologic intervention during study participation
- •Uncontrolled GI bleeding
- •Subjects who have disease limited to the rectum (maximum disease extent of less than 15 cm)
- •Women who are pregnant, breast-feeding, or planning to become pregnant during the study. All women of childbearing potential must have a negative serum pregnancy test at Screen 2 prior to randomization of treatment.
- •Women of childbearing potential not using adequate birth control measures (e.g., total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants).
- •Current or recent serious systemic disorder including clinically significant impairment in cardiac, pulmonary, liver, renal, endocrine, hematologic, or neurologic function, based on investigator discretion
- •Subjects currently receiving the following concomitant medications:
- •Prednisone or its equivalent at unstable doses or at doses exceeding 15 mg/day within 4 weeks prior to Day 0
- •Local steroids such as budesonide, Colifoam, or Predsol enemas within 2 weeks prior to Screen 2
- •Topical therapies, either mesalamine or steroids, taken within 2 weeks of Screen 2
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved a Clinical Response at Week 12
Time Frame: Week 12
Clinical response is defined as a reduction in the Mayo score of at least 3 points and at least a 30% reduction from Baseline, along with either a decrease from Baseline in the rectal bleeding subscore of more than 1 point or a rectal bleeding subscore of 0 or 1.
Secondary Outcomes
- Percent of Participants With a Modified Clinical Response(From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks)
- Percent of Participants With Increase in Diarrhea(From Day 0 through end of follow-up, up to 36 weeks)
- Time to Modified Clinical Response(From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed.)
- Percent of Participants With Healed Colonic Mucosa at Week 12(Week 12)
- Percent of Participants Who Achieved Remission at Week 12(Week 12)
- Percent of Participants With Colonoscopic Evidence of Visible Worm(From Day 0 through end of follow-up, up to 36 weeks)
- Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added(From Day 0 through Week 16)