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Study recruitment was difficult and not acheived
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Withdrawal of Oral Budesonide | Drug | The intervention arm will taper and stop budesonide therapy (withdrawal). |
|
| 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 |
| 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. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Joseph A Murray, MD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22345659 | Background | 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. | |
| 28017411 |
| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Continued Budesonide | Patients in this arm continued budesonide at the dose they were taking at the time of enrollment in the trial |
| FG001 | Withdrawal of Budesonide | Patients were weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial Withdrawal of Oral Budesonide: The intervention arm tapered and stoped budesonide therapy (withdrawal). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study was terminated due to recruitment being difficult and not achieved
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| ID | Title | Description |
|---|---|---|
| BG000 | Continued Budesonide | Patients in this arm continued budesonide at the dose they were taking at the time of enrollment in the trial |
| BG001 | Withdrawal of Budesonide | Patients were weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial Withdrawal of Oral Budesonide: The intervention arm tapered and stoped budesonide therapy (withdrawal). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 12 weeks |
|
Adverse Events were collected from baseline to end of study, approximately 2 weeks
Study was terminated due to recruitment being difficult and not achieved. There was no accrual in the Continued Budesonide arm
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Continued Budesonide | Patients in this arm continued budesonide at the dose they were taking at the time of enrollment in the trial |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
Study was terminated due to recruitment being difficult and not achieved.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph A. Murray, M.D. | Mayo Clinic | 507-284-2631 | Murray.Joseph@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 16, 2019 | Aug 3, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007410 | Intestinal Diseases |
| D002446 | Celiac Disease |
| D064068 | Collagenous Sprue |
| C538273 | Autoimmune enteropathy |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D008286 | Malabsorption Syndromes |
| D008659 | Metabolic Diseases |
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Randomized, open-label withdrawal of budesonide versus continued budesonide therapy in patients with immune-mediated enteropathies that have had symptomatic and histologic improvement
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| 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 |
| 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. |
| 17382600 | 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. |
| 20332526 | 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. |
| 28323276 | 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. |
| 8078529 | 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. |
| 9301500 | 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. |
| 12135030 | 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. |
| 27485029 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 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. | Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed. | Posted | 12 weeks |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Withdrawal of Budesonide | Patients were weaned off of budesonide over 2 weeks and continued off of the medication for the duration of the trial Withdrawal of Oral Budesonide: The intervention arm tapered and stoped budesonide therapy (withdrawal). | 0 | 1 | 0 | 1 | 1 | 1 |
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| D009750 | Nutritional and Metabolic Diseases |