Budesonide in Patients With Immune Mediated Enteropathies

NCT03866538 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 18-008639
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Enteropathy; Celiac Disease; CVID Enteropathy; Collagenous Sprue; Autoimmune Enteropathy

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Secondary Outcomes (9)

• Change in Symptoms

  12 weeks

• Change in Quality of Life: Celiac Disease Quality of Life Questionnaire (CD-QOL)

  12 weeks

• Change in Weight

  12 weeks

• Change in Iron

  12 weeks

• Change in Vitamin D

  12 weeks

Study Arms (2)

Continued Budesonide

NO INTERVENTION

Patients in this arm continue budesonide at the dose they were taking at the time of enrollment in the trial

Withdrawal of Budesonide

EXPERIMENTAL

Patients are weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial

Drug: Withdrawal of Oral Budesonide

Interventions

Withdrawal of Oral Budesonide DRUG

The intervention arm will taper and stop budesonide therapy (withdrawal).

Withdrawal of Budesonide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (9)

• 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.

  PMID: 22345659 BACKGROUND

• 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.

  PMID: 28017411 BACKGROUND

• 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.

  PMID: 17382600 BACKGROUND

• 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.

  PMID: 20332526 BACKGROUND

• 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.

  PMID: 28323276 BACKGROUND

• 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.

  PMID: 8078529 BACKGROUND

• 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.

  PMID: 9301500 BACKGROUND

• 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.

  PMID: 12135030 BACKGROUND

• 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.

  PMID: 27485029 BACKGROUND

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Intestinal Diseases; Celiac Disease; Collagenous Sprue; Autoimmune enteropathy

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Malabsorption Syndromes; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Study was terminated due to recruitment being difficult and not achieved.

Results Point of Contact

• Title: Joseph A. Murray, M.D.
• Organization: Mayo Clinic

Murray.Joseph@mayo.edu

507-284-2631

Study Officials

• Joseph A Murray, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, open-label withdrawal of budesonide versus continued budesonide therapy in patients with immune-mediated enteropathies that have had symptomatic and histologic improvement

Study Record Dates

• First Submitted: February 27, 2019
• First Posted: March 7, 2019
• Study Start: September 10, 2019
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: August 26, 2022
• Results First Posted: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)