Clinical trial NCT00048347
Conditions: Ulcerative Colitis
Keywords: Lymphocyte Monocyte Inflammation Th2 Colonoscopy Ulcerative Colitis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2002-10-01; Completion date: 2010-05-01
Enrollment: 18 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This study will evaluate the safety and effectiveness of the drug interferon-beta1a (AVONEX) in treating ulcerative colitis and examine the drug's effect on the immune system. People with ulcerative colitis have increased amounts of inflammatory chemicals (cytokines) made by immune cells in the lining of the colon. Studies have shown that interferon-beta may block the activity of these cytokines. Interferon-beta1a (AVONEX) is currently FDA-approved to treat multiple sclerosis, a disease involving inflammation of the brain and spinal cord.

Patients 18 years of age and older who have had ulcerative colitis for at least 4 months may be eligible for this study. Candidates will be screened with a review of their medical records, a medical history and physical examination, electrocardiogram (EKG), blood, urine, and stool tests, and a pregnancy test for women of childbearing potential. A colonoscopy will also be done to determine disease activity and extent. This test uses a lighted tube to examine the amount of inflammation in the colon and take tissue samples (biopsies) for testing. Before the test, the patient is given a medicine to allay anxiety and the discomfort of inserting the endoscope into the rectum. This flexible tube allows the doctor to see the intestinal mucosa and project an image of the inner lining of the intestine onto a TV monitor. At various places in the intestine, small pieces of tissue are plucked out by a special device at the tip of the endoscope. The procedure generally lasts 30 minutes to 1 hour.

Participants will come to the NIH Clinical Center once a week for 4 weeks to receive an injection of interferon-beta, fill out questionnaires, and have a symptoms check, physical examination, and blood tests. Patients whose colitis has not worsened at the end of the 4 weeks and who have not had significant drug side effects will continue to receive weekly injections for an additional 8 weeks. Some patients may receive some of the last eight injections outside of NIH, but all patients will visit the Clinical Center visits every 3 to 4 weeks for a physical exam, symptoms check and blood tests.

After the 12 injections are completed, patients will have another colonoscopy to evaluate the response to treatment and will return to the Clinical Center every 6 weeks for a total of four visits, for a physical examination, symptoms check and blood tests.

Detailed description:
The purpose of this pilot study is to evaluate the immunologic and clinical response to type I interferon administered to patients with ulcerative colitis. Ulcerative colitis (UC) is a chronic, relapsing inflammation of the colonic mucosa with major symptoms of diarrhea, hematochezia, abdominal pain, and an accompanying increase in colorectal carcinoma risk. Novel approaches to therapy of UC are required because the burden of disease is great (about 500,000 prevalent cases in the United States), standard medical therapy is limited in effectiveness and toxicity, and surgical therapy, albeit curative, results in permanent ostomies or complication-prone alternatives.

The rationale for this study is based on the observation that the mucosal inflammation in UC may be mediated by Th2 cytokines such as IL-4 or cytokines induced along with IL-4. Type I interferons can block IL-4 receptor signaling by up-regulating cytosolic inhibitory proteins (suppressor of cytokines signaling or SOCS proteins). Furthermore, two small studies of type I interferon effects on UC show benefit as opposed to many more studies in Crohn's disease, a classic Th1 inflammatory disease, which have shown no benefit from type I interferons. We hypothesize that type I interferons could be used to inhibit the pro-inflammatory signals of Th2 cytokines in UC.

This study will measure the immunologic and clinical effect of twelve weeks of treatment with a type I interferon administered to patients with active UC. The primary outcomes include documenting changes in immune parameters by measuring peripheral and lamina propria mononuclear cell cytokine release, expression levels of SOCS proteins in mononuclear cells, and changes in clinical parameters using the Short Clinical Colitis Activity Index and endoscopic and histologic scores. Secondary endpoints include the rate and severity of adverse events. Our short-term goal is to correlate changes in immune and biochemical parameters that accompany or predict clinical responses. The long-term goal of this study is to establish type I interferons as an effective alternative or adjunctive therapy with a low risk profile for the treatment of ulcerative colitis.

Arms: arm 1: Interferon-beta1a (Avonex) 30 µg IM every week for 12 weeks
Interventions: intervention 1: AVONEX
Intervention descriptions: intervention 1: 30µg IM every week for 12 weeks

Protocol documents: