Budesonide in Patients With Immune Mediated Enteropathies
Primary Purpose
Enteropathy, Celiac Disease, CVID Enteropathy
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Withdrawal of Oral Budesonide
Sponsored by
About this trial
This is an interventional treatment trial for Enteropathy
Eligibility Criteria
Inclusion Criteria
- Patients will be recruited from the Division of Gastroenterology and Hepatology and the Mayo Clinic in Rochester, MN.
- Adult patients with immune mediated enteropathies who have had improvement in symptoms and histology on oral budesonide therapy.
Exclusion Criteria
- Age <18 years
- Positive stool gluten testing in patients with refractory celiac disease
- Small bowel malignancy or history of small bowel malignancy
- Refractory celiac disease type 2
- Post-transplant lymphoproliferative disorder associated enteropathy
- No prior improvement in symptoms and histology with budesonide therapy
- Discontinuation of budesonide therapy prior to the trial
- Other concurrent systemic corticosteroids
- Other immune mediating medications, for example but not limited to azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, anti-TNF monoclonal antibodies, alpha-4 beta-7 integrin inhibiting monoclonal antibody, interleukin 12/23 inhibiting monoclonal antibody, JAK inhibitors.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Continued Budesonide
Withdrawal of Budesonide
Arm Description
Patients in this arm continue budesonide at the dose they were taking at the time of enrollment in the trial
Patients are weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial
Outcomes
Primary Outcome Measures
Change in Histology
Investigators will determine change in small bowel villi after withdrawal of budesonide compared to continued therapy to assess small intestinal injury. This will be accomplished by esophagogastroduodenoscopy (upper scope) with biopsies from the small intestine.
Secondary Outcome Measures
Change in Symptoms
Symptoms (monitored daily) will be compared between patients that withdraw from budesonide compared to those that continue budesonide therapy. Symptoms will be measured on the Celiac Disease Symptom Diary (CDSD) questionnaire. First question asks if subject has diarrhea and how many times. Second question asks if subject has spontaneous bowel movement and how many. Third question asks if subject had abdominal pain and to rate on a scale from 0 to 10 with higher numbers being worse pain. Fourth question asks if experiencing bloating and if it is very mild, mild, moderate, severe, or very severe. Fifth question asks if subject has nausea and if it is ranked very mild, mild, moderate, severe, or very severe. The sixth question asks if the subject has experienced tiredness and to rank very mild, mild, moderate, severe or very severe. Each question is evaluated for changes or trends over time, and a composite score including multiple questions can be calculated and compared.
Change in Quality of Life: Celiac Disease Quality of Life Questionnaire (CD-QOL)
Quality of life will be assessed monthly comparing those that withdraw from budesonide compared to those that continue therapy. This will be assessed by the Celiac Disease Quality of Life Questionnaire (CD-QOL). This survey includes 20 questions with scores for each ranging from 1 to 5, with higher numbers indicating improved quality of life. Total scores will range from 20 to 100 with higher numbers indicating better quality of life.
Change in Weight
Weight in kilograms will be monitored throughout the study. Changes will be compare between those withdrawing from budesonide compared to those continuing therapy.
Change in Iron
Iron in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Change in Vitamin D
25-hydroxy vitamin D in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Change in Vitamin B12
Vitamin B12 in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Change in Folate
Folate in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Change in Zinc
Zinc in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Change in Copper
Copper in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03866538
Brief Title
Budesonide in Patients With Immune Mediated Enteropathies
Official Title
Open-label Withdrawal Trial of Budesonide in Patients With Immune Mediated Enteropathies
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Study recruitment was difficult and not acheived
Study Start Date
September 10, 2019 (Actual)
Primary Completion Date
October 19, 2021 (Actual)
Study Completion Date
October 19, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Researchers are trying to determine if withdrawal of budesonide therapy in patients with immune-mediated enteropathies doing well on therapy will result in worsening symptoms, histology, quality of life, and micronutrient/nutritional status when compared to continued therapy.
Detailed Description
This study aims to evaluate patients with small intestinal diseases caused by the immune system (refractory celiac disease type 1, CVID enteropathy, autoimmune enteropathy, and collagenous enteropathy) who have had improvement in symptoms and small intestine healing with oral budesonide.
Patients who meet inclusion criteria and agree to enter the study will be included for 12 weeks or until they choose to discontinue or there are concerns for safety.
At the beginning of the study, patients will undergo questionnaires, blood draw, urine and stool collections, physical exam, and an upper scope (esophagogastroduodenoscopy) with biopsies from the small intestine. They will then be randomized to either continued therapy on their current dose and formulation of budesonide (medication provided by the study) or to withdrawal of the medication over 2 weeks and then no medication during the study. Daily questionnaire on symptoms will be recorded.
Patients will be assessed in the clinical research unit monthly during the study with a questionnaire, physical exam, blood draw, and urine/stool collections.
Finally, at the end of the trial (12 weeks) or at the time of withdrawal from the trial, the patients will complete questionnaires, physical exam, blood collection, urine/stool collection, and upper scope (esophagogastroduodenoscopy) with small bowel biopsies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Enteropathy, Celiac Disease, CVID Enteropathy, Collagenous Sprue, Autoimmune Enteropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized, open-label withdrawal of budesonide versus continued budesonide therapy in patients with immune-mediated enteropathies that have had symptomatic and histologic improvement
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Continued Budesonide
Arm Type
No Intervention
Arm Description
Patients in this arm continue budesonide at the dose they were taking at the time of enrollment in the trial
Arm Title
Withdrawal of Budesonide
Arm Type
Experimental
Arm Description
Patients are weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial
Intervention Type
Drug
Intervention Name(s)
Withdrawal of Oral Budesonide
Intervention Description
The intervention arm will taper and stop budesonide therapy (withdrawal).
Primary Outcome Measure Information:
Title
Change in Histology
Description
Investigators will determine change in small bowel villi after withdrawal of budesonide compared to continued therapy to assess small intestinal injury. This will be accomplished by esophagogastroduodenoscopy (upper scope) with biopsies from the small intestine.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in Symptoms
Description
Symptoms (monitored daily) will be compared between patients that withdraw from budesonide compared to those that continue budesonide therapy. Symptoms will be measured on the Celiac Disease Symptom Diary (CDSD) questionnaire. First question asks if subject has diarrhea and how many times. Second question asks if subject has spontaneous bowel movement and how many. Third question asks if subject had abdominal pain and to rate on a scale from 0 to 10 with higher numbers being worse pain. Fourth question asks if experiencing bloating and if it is very mild, mild, moderate, severe, or very severe. Fifth question asks if subject has nausea and if it is ranked very mild, mild, moderate, severe, or very severe. The sixth question asks if the subject has experienced tiredness and to rank very mild, mild, moderate, severe or very severe. Each question is evaluated for changes or trends over time, and a composite score including multiple questions can be calculated and compared.
Time Frame
12 weeks
Title
Change in Quality of Life: Celiac Disease Quality of Life Questionnaire (CD-QOL)
Description
Quality of life will be assessed monthly comparing those that withdraw from budesonide compared to those that continue therapy. This will be assessed by the Celiac Disease Quality of Life Questionnaire (CD-QOL). This survey includes 20 questions with scores for each ranging from 1 to 5, with higher numbers indicating improved quality of life. Total scores will range from 20 to 100 with higher numbers indicating better quality of life.
Time Frame
12 weeks
Title
Change in Weight
Description
Weight in kilograms will be monitored throughout the study. Changes will be compare between those withdrawing from budesonide compared to those continuing therapy.
Time Frame
12 weeks
Title
Change in Iron
Description
Iron in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
Title
Change in Vitamin D
Description
25-hydroxy vitamin D in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
Title
Change in Vitamin B12
Description
Vitamin B12 in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
Title
Change in Folate
Description
Folate in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
Title
Change in Zinc
Description
Zinc in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
Title
Change in Copper
Description
Copper in the blood will be compared to those that withdraw from budesonide compared to those that continue therapy. This will be assessed at the initiation and completion of the trial.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients will be recruited from the Division of Gastroenterology and Hepatology and the Mayo Clinic in Rochester, MN.
Adult patients with immune mediated enteropathies who have had improvement in symptoms and histology on oral budesonide therapy.
Exclusion Criteria
Age <18 years
Positive stool gluten testing in patients with refractory celiac disease
Small bowel malignancy or history of small bowel malignancy
Refractory celiac disease type 2
Post-transplant lymphoproliferative disorder associated enteropathy
No prior improvement in symptoms and histology with budesonide therapy
Discontinuation of budesonide therapy prior to the trial
Other concurrent systemic corticosteroids
Other immune mediating medications, for example but not limited to azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, anti-TNF monoclonal antibodies, alpha-4 beta-7 integrin inhibiting monoclonal antibody, interleukin 12/23 inhibiting monoclonal antibody, JAK inhibitors.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph A Murray, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22345659
Citation
Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. doi: 10.1136/gutjnl-2011-301346. Epub 2012 Feb 16.
Results Reference
background
PubMed Identifier
28017411
Citation
Choung RS, Unalp-Arida A, Ruhl CE, Brantner TL, Everhart JE, Murray JA. Less Hidden Celiac Disease But Increased Gluten Avoidance Without a Diagnosis in the United States: Findings From the National Health and Nutrition Examination Surveys From 2009 to 2014. Mayo Clin Proc. 2016 Dec 5:S0025-6196(16)30634-6. doi: 10.1016/j.mayocp.2016.10.012. Online ahead of print.
Results Reference
background
PubMed Identifier
17382600
Citation
Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol. 2007 Apr;5(4):445-50. doi: 10.1016/j.cgh.2006.12.006. Epub 2007 Mar 26.
Results Reference
background
PubMed Identifier
20332526
Citation
Rubio-Tapia A, Murray JA. Classification and management of refractory coeliac disease. Gut. 2010 Apr;59(4):547-57. doi: 10.1136/gut.2009.195131.
Results Reference
background
PubMed Identifier
28323276
Citation
Mukewar SS, Sharma A, Rubio-Tapia A, Wu TT, Jabri B, Murray JA. Open-Capsule Budesonide for Refractory Celiac Disease. Am J Gastroenterol. 2017 Jun;112(6):959-967. doi: 10.1038/ajg.2017.71. Epub 2017 Mar 21.
Results Reference
background
PubMed Identifier
8078529
Citation
Greenberg GR, Feagan BG, Martin F, Sutherland LR, Thomson AB, Williams CN, Nilsson LG, Persson T. Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. N Engl J Med. 1994 Sep 29;331(13):836-41. doi: 10.1056/NEJM199409293311303.
Results Reference
background
PubMed Identifier
9301500
Citation
Campieri M, Ferguson A, Doe W, Persson T, Nilsson LG. Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group. Gut. 1997 Aug;41(2):209-14. doi: 10.1136/gut.41.2.209.
Results Reference
background
PubMed Identifier
12135030
Citation
Tremaine WJ, Hanauer SB, Katz S, Winston BD, Levine JG, Persson T, Persson A; Budesonide CIR United States Study Group. Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States. Am J Gastroenterol. 2002 Jul;97(7):1748-54. doi: 10.1111/j.1572-0241.2002.05835.x.
Results Reference
background
PubMed Identifier
27485029
Citation
Rubio-Tapia A, Malamut G, Verbeek WH, van Wanrooij RL, Leffler DA, Niveloni SI, Arguelles-Grande C, Lahr BD, Zinsmeister AR, Murray JA, Kelly CP, Bai JC, Green PH, Daum S, Mulder CJ, Cellier C. Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry. Aliment Pharmacol Ther. 2016 Oct;44(7):704-14. doi: 10.1111/apt.13755. Epub 2016 Aug 3.
Results Reference
background
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Budesonide in Patients With Immune Mediated Enteropathies
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