Clinical trial NCT03866538: Budesonide in Patients With Immune Mediated Enteropathies
Official title: Open-label Withdrawal Trial of Budesonide in Patients With Immune Mediated Enteropathies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Enteropathy
Celiac Disease
CVID Enteropathy
Collagenous Sprue
Autoimmune Enteropathy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2019-03-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Histology
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Symptoms
timeFrame: 12 weeks
measure: Change in Quality of Life: Celiac Disease Quality of Life Questionnaire (CD-QOL)
timeFrame: 12 weeks
measure: Change in Weight
timeFrame: 12 weeks
measure: Change in Iron
timeFrame: 12 weeks
measure: Change in Vitamin D
timeFrame: 12 weeks
measure: Change in Vitamin B12
timeFrame: 12 weeks
measure: Change in Folate
timeFrame: 12 weeks
measure: Change in Zinc
timeFrame: 12 weeks
measure: Change in Copper
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Joseph A Murray, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.