Inflammatory Bowel Disease, Ulcerative Colitis
Conditions
Keywords
Inflammatory Bowel Disease, Ulcerative Colitis, Budesonide, Corticosteroids
Brief summary
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).
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.
Interventions
DRUGCombination 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.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Simple Clinical Colitis Disease Activity (SCCAI) | 0, 2, 4, 6, and 8 weeks | 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) | Week 0 and 8 | Scores range from 10-70 where higher scores indicated better quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACTH Stimulation Test | Week 16 | 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 | 0, 2, 4, 6, 8, 11, 14, 20, 26, and 52 weeks | — |
| C Reactive Protein | Week 0 and 8 | Higher values indicated increased disease activity |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination Oral Budesonide and Rectal Hydrocortisone Intervention Arm | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | Combination Oral Budesonide and Rectal Hydrocortisone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Short Inflammatory Bowel Disease Questionnaire (SIBDQ)
Scores range from 10-70 where higher scores indicated better quality of life.
Time frame: Week 0 and 8
Population: The only patient enrolled withdrew; there was no data to analyze.
Primary
Simple Clinical Colitis Disease Activity (SCCAI)
Scores range from 0-19. Higher scores indicated increased disease severity. A score less than 3 is consistent with clinical remission.
Time frame: 0, 2, 4, 6, and 8 weeks
Population: The only patient enrolled withdrew; there was no data to analyze.
Secondary
ACTH Stimulation Test
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.
Time frame: Week 16
Population: The only patient enrolled withdrew; there was no data to analyze.
Secondary
Adverse Events
Time frame: 0, 2, 4, 6, 8, 11, 14, 20, 26, and 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Oral Budesonide and Rectal Hydrocortisone | Adverse Events | 2 Adverse events |
Secondary
C Reactive Protein
Higher values indicated increased disease activity
Time frame: Week 0 and 8
Population: The only patient enrolled withdrew; there was no data to analyze.