The Use of Oral Budesonide and Rectal Hydrocortisone for the Treatment of Active Ulcerative Colitis

This study has been terminated.
(Study terminated due to insufficient enrollment)
Sponsor:
Information provided by (Responsible Party):
University of Maryland
ClinicalTrials.gov Identifier:
NCT00805285
First received: December 8, 2008
Last updated: March 30, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Inflammatory Bowel Disease
Ulcerative Colitis
Drug: Combination Oral Budesonide and Rectal Hydrocortisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Oral Budesonide and Rectal Hydrocortisone for the Treatment of Extensive Ulcerative Colitis: A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Simple Clinical Colitis Disease Activity (SCCAI) [ Time Frame: 0, 2, 4, 6, and 8 weeks ] [ Designated as safety issue: No ]
    Scores range from 0-19. Higher scores indicated increased disease severity. A score less than 3 is consistent with clinical remission.

  • Short Inflammatory Bowel Disease Questionnaire (SIBDQ) [ Time Frame: Week 0 and 8 ] [ Designated as safety issue: No ]
    Scores range from 10-70 where higher scores indicated better quality of life.


Secondary Outcome Measures:
  • ACTH Stimulation Test [ Time Frame: Week 16 ] [ Designated as safety issue: Yes ]
    An increase in cortisol after stimulation by ACTH is normal. Blood cortisol after ACTH stimulation should be greater than 18 - 20 mcg/dL, depending on the dose of cosyntropin used.

  • Adverse Events [ Time Frame: 0, 2, 4, 6, 8, 11, 14, 20, 26, and 52 weeks ] [ Designated as safety issue: Yes ]
  • C Reactive Protein [ Time Frame: Week 0 and 8 ] [ Designated as safety issue: No ]
    Higher values indicated increased disease activity


Enrollment: 2
Study Start Date: October 2008
Study Completion Date: March 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Oral Budesonide and Rectal Hydrocortisone
See intervention
Drug: Combination Oral Budesonide and Rectal Hydrocortisone
Budesonide 9 mg PO (oral) daily and hydrocortisone 100 mL PR (enema) for an 8-week period. The doses of each drug to be used in the pilot study are standard doses used in clinical practice. After 8-weeks, the budesonide will be tapered in the following manner: 1) budesonide 6 mg PO daily and hydrocortisone 100 ml PR every other day (EOD) for 3 weeks then 2) budesonide 3 mg PO daily and hydrocortisone 100 ml PR 2 x per week for 3 weeks then 3) discontinue budesonide.
Other Name: Entocort

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 oral budesonide in patients with UC is less extensive. However, the data regarding the efficacy of topical therapy for left-sided UC is extensive. Randomized controlled trials of budesonide enemas have demonstrated similar efficacy and safety profile to hydrocortisone enemas in the induction of remission of left sided UC. We have chosen to utilize hydrocortisone enemas in our study as it is widely available in the United States.

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 oral budesonide and rectal hydrocortisone 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 16, 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 budesonide and topical hydrocortisone 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805285

Locations
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Raymond K Cross, MD, MS University of Maryland
Study Chair: Leyla J Ghazi, MD University of Maryland
  More Information

Additional Information:
No publications provided

Responsible Party: University of Maryland
ClinicalTrials.gov Identifier: NCT00805285     History of Changes
Other Study ID Numbers: H-30365
Study First Received: December 8, 2008
Results First Received: January 24, 2013
Last Updated: March 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
Inflammatory Bowel Disease
Ulcerative Colitis
Budesonide
Corticosteroids

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Inflammatory Bowel Diseases
Intestinal Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Budesonide
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 23, 2014