Budesonide in Patients With Immune Mediated Enteropathies

Celiac Disease Clinical Trial

Official title:

Open-label Withdrawal Trial of Budesonide in Patients With Immune Mediated Enteropathies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03866538
• Other study ID #: 18-008639
• Status: Terminated
• Phase: Phase 4
• Start date: September 10, 2019
• Est. completion date: October 19, 2021

Study information

• Verified date: August 2022
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 19, 2021
• Est. primary completion date: October 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Enteropathy
• Celiac Disease
• Collagenous Sprue
• CVID Enteropathy
• Enteropathy
• Intestinal Diseases

Intervention

Drug:
• Withdrawal of Oral Budesonide
The intervention arm will taper and stop budesonide therapy (withdrawal).

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View 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. pii: S0025-6196(16)30634-6. doi: 10.1016/j.mayocp.2016.10.012. [Epub ahead of print] — View 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. — View 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. Epub 2007 Mar 26. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks

External Links

•   Mayo Clinic Clinical Trials