Autoimmune Enteropathy, Celiac Disease, Collagenous Sprue, CVID Enteropathy, Enteropathy
Conditions
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.
Interventions
DRUGWithdrawal of Oral Budesonide
The intervention arm will taper and stop budesonide therapy (withdrawal).
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Histology | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life: Celiac Disease Quality of Life Questionnaire (CD-QOL) | 12 weeks | 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. |
| Change in Weight | 12 weeks | Weight in kilograms will be monitored throughout the study. Changes will be compare between those withdrawing from budesonide compared to those continuing therapy. |
| Change in Iron | 12 weeks | 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. |
| Change in Vitamin D | 12 weeks | 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. |
| Change in Symptoms | 12 weeks | 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. |
| Change in Folate | 12 weeks | 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. |
| Change in Zinc | 12 weeks | 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. |
| Change in Copper | 12 weeks | 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. |
| Change in Vitamin B12 | 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Continued Budesonide Patients in this arm continued budesonide at the dose they were taking at the time of enrollment in the trial | 0 |
| 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). | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Withdrawal of Budesonide | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 1 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.
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.
Time frame: 12 weeks
Population: Study was terminated due to recruitment being difficult and not achieved. Data was not collected nor analyzed.