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
Trial status: Open for Enrollment
Why is this study being done?
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.
The cause of UC 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.
Who is eligible to participate?
1. Subject has provided written informed consent
2. 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.
3. Mayo score ≥ 4, as scored at Screen 2
4. If taking the following medications at Screen 1, subjects must meet the following criteria:
1. Oral Corticosteroids: stable treatment for at least 4 weeks prior to Day 0 with a maximum dose equivalent to ≤ 15 mg/day of prednisone
2. 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
3. Aminosalicylates: stable oral doses up to 4.8 g/day for at least 4 weeks prior to Day 0
1. Subjects whose UC is anticipated to require surgical, endoscopic, or radiologic intervention during study participation
2. Uncontrolled GI bleeding
3. Subjects who have disease limited to the rectum (maximum disease extent of less than 15 cm)
4. 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.
5. 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)
6. Current or recent serious systemic disorder including clinically significant impairment in cardiac, pulmonary, liver, renal, endocrine, hematologic, or neurologic function, based on investigator discretion
7. Subjects currently receiving the following concomitant medications:
1. Prednisone or its equivalent at unstable doses or at doses exceeding 15 mg/day within 4 weeks prior to Day 0
2. Local steroids such as budesonide, Colifoam, or Predsol enemas within 2 weeks prior to Screen 2
3. Topical therapies, either mesalamine or steroids, taken within 2 weeks of Screen 2.
4. Non-steroidal anti-inflammatory drugs (NSAIDs), Cyclooxygenase (COX)-2 inhibitors, or aspirin >100 mg/day within 2 weeks prior to Screen 2
5. TNF-alpha inhibitors including but not limited to infliximab (Remicade) or adalimumab (Humira) within 12 weeks of Day 0
6. Any biological agent within 12 weeks of Day 0
7. Metronidazole within 4 weeks of Day 0
8. Receipt of any investigational agent within the 12 weeks prior to Day 0
9. Antibacterial or oral antifungal agents within 4 weeks of Screen 2
10. IFN therapy
8. Blood transfusion within the 12 weeks prior to Day 0
9. Presence of any of the following abnormal laboratory parameters at Screen 1:
1. Hemoglobin < 10.0 g/dL
2. White Blood Count (WBC) < 4,000 or > 20,000/L (equivalent to WBC < 4 or > 20 x109/L)
3. Platelets < 100,000 or > 800,000/L (equivalent to platelets < 100 or > 800 x109/L)
4. Total bilirubin > 1.5 × Upper limit of normal (ULN)
5. Alanine transaminase (ALT) > 2 × ULN
6. Aspartate transaminase (AST) > 2 × ULN
7. Alkaline phosphatase (ALK) > 1.5 × ULN
8. Gamma-glutamyl transferase (GGT) > 1.5 × ULN
9. Creatinine > 1.5 × ULN
10. History of drug or alcohol abuse within one year prior to Day 0
11. Inability to understand the nature and requirements of the study, or to comply with the study procedures or planned schedule of study visits
12. Evidence of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
13. Active infection with C. difficile, bacterial enteric pathogens, or pathogenic ova/parasites
14. History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I
15. History of colonic dysplasia
16. Any social or medical condition that, in the opinion of the investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.