The Use of Budesonide for the Treatment of Active Ulcerative Colitis

Condition(s) targeted: Inflammatory Bowel Disease; Ulcerative Colitis

Intervention: Combination Oral and Rectal Budesonide (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Maryland

Official(s) and/or principal investigator(s):
Raymond K Cross, MD, MS, Principal Investigator, Affiliation: University of Maryland
Leyla J Ghazi, MD, Study Chair, Affiliation: University of Maryland

Overall contact:
Raymond K Cross, MD, MS, Phone: 410-706-3387, Ext: 3, Email: rcross@medicine.umaryland.edu

The purpose of this study is to evaluate if the combination of oral and rectal budesonide improves symptoms in patients with active ulcerative colitis. Also, we would like to determine if oral and rectal budesonide has fewer and less severe side effects compared to standard steroids (prednisone).

Official title: ORAL AND RECTAL BUDESONIDE FOR THE TREATMENT OF EXTENSIVE ULCERATIVE COLITIS: A PILOT STUDY

Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

Clinical Colitis Disease Activity (SCCAI)

Quality of Life (SIBDQ)

Secondary outcome:

Adrenal Function (ACTH Stimulation Test)

Adverse Events

Inflammatory Markers

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Written, voluntary, informed consent given

- 18 years or older

- Speak and read English

- Extensive ulcerative colitis based upon endoscopy, histopathology, and clinical

symptoms

- SCCAI Score > 3

- Presence of diarrhea (3 or more bowel movements per 24 hours) AND grossly visible

blood in stool

Exclusion Criteria:

- Serum creatinine > 2. 0 mg/dL

- Pregnant or breastfeeding

- Prior history of total or subtotal colectomy, or currently has an ostomy

- History or suspicion of Crohn's disease or Indeterminate colitis

- Diagnosis of any condition deemed by the investigator inhibiting completion of the

trial

- Initiated therapy with or change in mesalamine dose within the last 4 weeks

- Change in azathioprine, 6-mercaptopurine, or cyclosporine within the last 8 weeks

- Currently taking or have used corticosteroids within the last 8 weeks

- Rectally administered mesalamine or steroids within the last 2 weeks

- Current or prior use of anti-TNF alpha agents within the last 8 weeks

- Experimental ulcerative colitis agents within the last 8 weeks

- Concomitant use of CYP3A4 activity inhibitor (e. g. ketoconazole, itraconazole,

ritonavir, indinavir, erythromycin)

- Uncontrolled diabetes (HgA1c > 8. 0) within 1 year

- Unstable Coronary artery disease/Class III/IV CHF

- Decompensated cirrhosis (e. g. encephalopathy, renal failure, ascites, GIB)

- Any known infection requiring antibiotics

- Active Clostridium difficile infection

- COPD requiring home oxygen

- HIV/AIDS with CD4 < 200 or AIDs-defining illnesses/infections

Raymond K Cross, MD, MS, Phone: 410-706-3387, Ext: 3, Email: rcross@medicine.umaryland.edu

University of Maryland, Baltimore, Maryland 21201, United States; Recruiting
Leyla J Ghazi, MD, Phone: 410-706-3387, Ext: 3, Email: Lghazi@medicine.umaryland.edu
Raymond K Cross, MD, MS, Principal Investigator

University of Maryland IBD Program

Starting date: October 2008
Ending date: January 2010
Last updated: December 8, 2008