Budesonide in Patients With Immune Mediated Enteropathies

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Collagenous Sprue, Enteropathy, Celiac Disease, CVID Enteropathy, Autoimmune Enteropathy

Intervention / Treatment
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* Drug: Withdrawal of Oral Budesonide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Continued Budesonide<br>Patients in this arm continue budesonide at the dose they were taking at the time of enrollment in the trial | |
| Experimental: Withdrawal of Budesonide<br>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<br>* The intervention arm will taper and stop budesonide therapy (withdrawal).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |