| City: |
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Baltimore |
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State:
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MD |
| Zip Code: |
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21201 |
| Conditions: |
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Inflammatory Bowel Disease - Ulcerative Colitis |
| Purpose: |
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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).
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| Study summary: |
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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. |
| Criteria: |
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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 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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August 16, 2010 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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