• Clinical Colitis Disease Activity (SCCAI) [ Time Frame: Q 2-3 Weeks ] [ Designated as safety issue: No ]
  
• Quality of Life (SIBDQ) [ Time Frame: Week 0 and 8 ] [ Designated as safety issue: No ]
  

• Adrenal Function (ACTH Stimulation Test) [ Time Frame: Week 0 and 8 ] [ Designated as safety issue: Yes ]
  
• Adverse Events [ Time Frame: Q 2-3 Weeks ] [ Designated as safety issue: Yes ]
  
• Inflammatory Markers [ Time Frame: Week 0 and 8 ] [ Designated as safety issue: No ]
  

Ulcerative colitis (UC) is a common chronic inflammatory condition of the intestines that results in bloody diarrhea, abdominal pain, and extraintestinal manifestations of disease. The disease course is typically chronic, characterized by periodic exacerbations followed by symptom- free intervals; less commonly symptoms are continuous and unrelenting. The symptoms and disease course have a profound, detrimental impact on the quality of life in patients with UC.

The initial therapeutic approach depends upon both the extent of colonic involvement and the severity of the disease process at presentation. Typically, patients are treated based on a pyramid or "Step up" approach. If patients have mild symptoms, they receive less powerful therapies lower in the pyramid with fewer side effects. Patients with disease confined to distal colon are typically treated with topical therapies including either 5-ASA or steroid enemas. However, as symptoms worsen or if severe at the time of diagnosis, patients receive more aggressive therapies higher in the pyramid including steroids. Despite medical therapy, 50% will have colectomy or become steroid dependent one year after receiving steroids.

Steroids are associated with significant side effects. Adverse consequences of steroids are related to dose and duration of exposure, and include but are not limited to cosmetic side effects, ocular disease (glaucoma, cataracts), diabetes, hypertension, vascular disease, osteoporosis, neuropsychiatric complications, and increased risk of infection.

Newer "designer" corticosteroids including budesonide have reduced systemic bioavailability and high local anti-inflammatory activity; as a result it is associated with fewer and less severe side effects. Studies have proven the efficacy of budesonide in inducing remission in active Crohn's disease. However, the data for the use of budesonide in patients with UC is less extensive.

Budesonide is available in oral and suspension enema forms. No studies to date have been performed to evaluate the combination of oral and rectal budesonide for induction of remission in patients with active extensive ulcerative colitis. Further, it is not known whether a combination of oral and rectal budesonide would be better tolerated than conventional steroids (prednisone).

A 52-week open-label pilot study will be performed at the University of Maryland Medical Center. Subjects will include patients with previously or newly diagnosed extensive ulcerative colitis. Patients will be treated with both oral and rectal budesonide for 8 weeks followed by a predetermined taper. All patients will undergo research clinic visits at enrollment and week 8. During these visits, patients will complete a series of questionnaires that measure the patient's disease activity, quality of life, side effects, medical compliance, and other parameters. Blood draws and stool studies are required at each study visit to monitor blood counts, electrolytes, liver function, inflammatory markers, and adrenal function. Additionally, at week 8, an ACTH (cosyntropin) stimulation test will be performed. After obtaining a basal cortisol level, 250 ug of cosyntropin is given intravenously. Plasma samples of cortisol will then be drawn at 30 minutes to assess for adrenal insufficiency. Close follow-up with eight 30-min telephone sessions (every 2-3 weeks) will also be conducted to assess disease activity and adverse events.

The goal of this study is to determine whether combination therapy using oral and topical budesonide will result in the induction of remission in patients with active extensive ulcerative colitis. Further, we aim to show that combination therapy is better tolerated and has less severe side effects compared to conventional therapy with prednisone.