Interferon-beta1a (AVONEX) Treatment of Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: AVONEX
Intervention description: 30µg IM every week for 12 weeks
Intervention MeSH terms: Interferon beta-1a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphocyte; Monocyte; Inflammation; Th2; Colonoscopy; Ulcerative Colitis

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age 18 years old or greater.

               2. Diagnosis of ulcerative colitis for at least 4 months based on endoscopic
                  appearance or radiographic distribution of disease and corroborated with
                  histopathology (especially the absence of granulomata).

               3. Presence of current active disease as defined by a Simple Clinical Colitis
                  Activity Index of greater than or equal to 5 (for either of the two measurements
                  done during the Screening Phase and that the second measurement is within 50
                  percent of the value of the first) who may or may not have the presence of one of
                  the following: current corticosteroid- dependence for disease treatment, disease
                  refractory to corticosteroids, or history of intolerance to treatment with
                  corticosteroids (for criterion of co-administered corticosteroid dose see below).

                  Corticosteroid-dependence is defined as relapse of ulcerative colitis within 60
                  days of completing a course of corticosteroid treatment, or during corticosteroid
                  tapering at doses greater than or equal to 10 mg prednisone/day (or equivalent),
                  or within three months following corticosteroid tapering while receiving a
                  steroid dose of greater than or equal to 10 mg prednisone/day (or equivalent).

               4. If currently receiving medication for ulcerative colitis, patients may be on a
                  stable regimen of one or a combination of the following drug doses and durations:

        Corticosteroids (less than or equal to 25 mg Prednisone/d or Prednisone equivalent) is
        greater than or equal to 4 weeks;

        5-ASA/Sulfasalazine is greater than or equal to 4 weeks;

        Azathioprine/6-MP/thioguanine is greater than or equal to 12 weeks. (Note: Patients
        receiving azathioprine/6-MP/thioguanine must have been on a stable dose of this medication
        for greater than or equal to 8 weeks before randomization);

        Probiotics (live bacterial dietary supplements) greater than or equal to 4 weeks;

        Prebiotics (dietary supplements to produce biologically active substances) greater than or
        equal to 4 weeks.

        5. Use of barrier or hormonal methods of birth control for female subjects who are not
        surgically sterile or postmenopausal.

        6. Negative serum beta-hCG for women of child-bearing potential (women who are not
        surgically sterile or postmenopausal) to exclude early unnoticed pregnancy.

        7. Negative results on stool examination for culture of enteric pathogens (Salmonella,
        Shigella, Yersinia, Campylobacter, Vibrio, E. coli O157/H7), Clostridium difficile toxin
        assay, enteric parasites and their ova (including Giardia and Cryptosporidia).

        8. Thyroid function test and TSH level within establish normal range set by the Clinical
        Center.

        EXCLUSION CRITERIA:

          1. Inability to meet any of the above inclusion criteria.

          2. Use of any of the following medications within the specified time period prior to the
             first dose of interferon-beta or at any time during the study:

             Non-steroidal anti-inflammatory agents (including COX-2 inhibitors), - 1 week

             Corticosteroids (greater than 25 mg Prednisone/d or Prednisone equivalent),
             Methotrexate, Cyclosporin, Tacrolimus, Thalidomide, or Mycophenolate mofetil - 4 weeks

             Monoclonal antibodies to TNF alpha or any Other Biologic (cytokine, anti-cytokine, or
             integrin-based therapy, for instance) - 4 months

             Any experimental agent - 1 month

             Concomitant use of any of the following drugs: isoniazid, iproniazid, dantrolene,
             ticrynafen (tienilic acid), ibufenac, bromfenac, benoxaprofen, zileutan, nicotinic
             acid, trovafloxacin, perhexiline, dilevavol, labetalol, pemoline, felbamate,
             tolcapone, diclofenac, AIDS drugs (HIV+ subjects are excluded anyway), and
             troglitozone.

          3. History of colectomy, partial colectomy, current ostomy, or pouchitis.

          4. Presence of significant electrocardiogram abnormalities including QT(c) greater than
             or equal to 0.48 sec, Mobitz type II second degree or third degree atrioventricular
             block, left bundle branch block or right bundle branch block accompanied by any
             fascicular block, changes consistent with acute ischemia or pericarditis.

          5. Presence of a diagnosis of Crohn's disease, indeterminate colitis, microscopic
             colitis, ischemic colitis, or colitis attributable to infection. This determination
             may require use of clinical, endoscopic, and histologic data.

          6. Presence of Cushing's syndrome.

          7. Presence of current active bowel obstruction, intestinal perforation, significant GI
             hemorrhage, known presence of high grade stricture, history of toxic megacolon,
             history of colonic epithelium high-grade dysplasia or a dysplasia-associated lesion or
             mass that does not resemble an adenoma (that is a mass lesion, stricture, or
             broad-based tumor).

          8. Anticipation that surgery may be required to treat the ulcerative colitis within 3
             months of study entry.

          9. HIV positivity or signs and symptoms consistent with HIV infection.

         10. Acute systemic or intestinal infection requiring antibiotics.

         11. Active hepatitis B or C.

         12. Decompensated liver disease (Childs-Pugh class B or C).

         13. Hematocrit less than 30 percent

             Platelet count 120,000 less than or greater than 850,000

             PT INR greater than 1.3 or PTT prolonged by greater than 3 seconds

             Serum creatinine or BUN greater than 1.5 times the upper limit of normal (ULN)

             ALT (SGPT) or AST (SGOT) greater than 2 times the ULN

             Total bilirubin greater than 1.25 times the ULN

             Alkaline phosphatase greater than 1.5 times the ULN.

         14. Pregnancy or nursing (for women).

         15. History of cancer (other than resected cutaneous basal or squamous cell carcinoma and
             in situ cervical cancer) with less than 5 years' documentation of a disease-free
             state.

         16. History of a myocardial infarction within the last 12 months.

         17. Any other condition that in the investigator's opinion places the patient at undue
             risk by participating in the study. This includes but is not limited to: psoriasis,
             thyroid disease, myasthenia gravis, lupus erythematosus, rheumatoid arthritis,
             Raynaud's disease, autoimmune hepatitis, C1 esterase deficiency or any deficiency of
             the complement system, and plasma cell dyscrasias.

         18. History of anaphylactic reaction or hypersensitivity to natural or recombinant
             interferon-beta, human albumin, or proteins derived from CHO cells/formulation.

         19. History of depression with psychotic features, or requiring ECT or hospitalization, or
             accompanied by suicidal ideation, gestures, or attempts.

         20. History of seizure, except for isolated febrile seizure of childhood.