Connective Tissue Disorders, Eosinophilic Esophagitis
Conditions
Keywords
Eosinophilic Esophagitis, Connective Tissue Disorders, Drug trial
Brief summary
The purpose of this research study is to test the safety of losartan potassium and see what effects (good and bad) it has on you and your eosinophilic esophagitis.
Detailed description
Losartan is a drug that is approved by the United States Food and Drug Administration (FDA) for use in adults and children over 6 years of age who have high blood pressure. Losartan has been safe when administered to patients with normal blood pressure. This medication has not been studied in people with eosinophilic esophagitis or connective tissue disorder. Eosinophils are a type of white blood cell that induces inflammation. Eosinophils with other inflammatory cells produce a protein called TGF-β, which may contribute to part of EoE. Losartan may reduce the amount of this protein and therefore, be a treatment for eosinophilic esophagitis. You will be in the research study for approximately 4 months. Participation in this research study will involve 9 study visits. Of the 9 study visits, at least 3 visits will take place in the clinic; the other visits may take place over the telephone. Throughout the study, the following activities will occur: 1. A physical and vital signs will be obtained 2. There will be two endoscopies performed one at the beginning and one at the end of the study 3. Blood will be obtained up to three times 4. Pregnancy tests will be performed 5. Quality-of-life questionnaires will be completed This is an open-label trial, which means that if you choose to enroll and you meet screening criteria, you will receive Losartan as a treatment. You will start the study drug at a low dose. It will be increased at vist 3 the 1 month visit. The dose of study drug will be increased depending on your weight and how well you tolerate each dose but will not exceed 100mg of study drug per day. It may be increased or decreased during the study if there are any side effects. If you do not have certain side effects, you will take each dose of the study drug between 21 and 28 days until your next study visit. You will swallow a pill or liquid once or twice a day. This study will consist of 4 phases: screening, treatment (titration and maintenance), end of treatment, and follow-up. Participants that are between 5 to 18 years of age, as well as the parent or legal guardian will be asked to complete questionnaires of quality-of-life symptom severity questionnaires. Participants between the age of 19 and 21 will also have to fill out these questionnaires, but parents/guardians will not have to fill these out. If you are the parent or caretaker, the only study activity in which you will be involved is the completion of questionnaires about you and your family.
Interventions
DRUGLosartan Potassium
The dose of study drug is dependent on body weight and tolerance but did not exceed 100 mg.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is an open-label study which means that all participants receive the study medicine
Eligibility
Sex/Gender
ALL
Age
5 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of eosinophilic esophagitis. 2. Have been on a high dose proton pump inhibitor for at least 8 weeks prior to a diagnostic endoscopy of eosinophilic esophagitis without histologic resolution. 3. Agree to maintain the same diet throughout the duration of the study. 4. If participant is female: meet one of the following criteria: 1. Is of non-childbearing potential (pre-menarchal or surgically sterile with documentation) 2. Is of childbearing potential with a negative urine pregnancy test at screening.
Exclusion criteria
1. Past or planned cardiac surgeries. 2. Had an aortic root Z-score greater than 3 on a previous echocardiogram. 3. Have intolerance to the study agent such as angioedema, IgE-mediated allergy. 4. Have renal dysfunction with creatinine in excess of the upper normal limit for age. 5. Have another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome, Churg Strauss vasculitis, eosinophilic granuloma, or a parasitic infection). 6. Diagnosed with hepatic insufficiency. 7. History of abnormal gastric or duodenal biopsy or documented gastrointestinal (GI) disorders (e.g., Celiac Disease, Crohn's disease or helicobacter pylori infection.), not including chronic gastritis, chronic duodenitis, mucosal eosinophilia or other eosinophilic gastrointestinal disorders. 8. Used anti-immunoglobulin E \[IgE\] mAb, anti-tumor necrosis factor \[TNF\] mAb, anti-IL-5 agents, or anti-IL-13 within the last six months. 9. Used methotrexate, cyclosporine, interferon-α, or other systemic immunosuppressive or immunomodulating agents within the last three months. 10. Have a history of a stricture during an endoscopy procedure that prevents passage of the endoscope. 11. Taking or plan to take an angiotensin II receptor blocker (ARB) therapy, angiotensin-converting enzyme inhibitor (ACEI), beta blocker therapy (BB), or calcium channel blocker at the screening visit or at any time during the study, or have you been taking any of these medications for the last three months. 12. If the participant is female: pregnant or nursing. 13. Taking any investigative drug or device study within the last 30 days. 14. Had participated in any investigative biologics study within the last three months prior to the study entry. 15. Taking or plan to take hydrochlorothiazide, warfarin, cimetidine, phenobarbital, rifampin, or fluconazole. 16. If the participant is female: using a medically accepted effective method of birth control. 17. Will be able to complete all study procedures including endoscopy. 18. Taking or plan to take potassium supplements or salt substitutes containing potassium.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants in Histologic Remission at 16 Weeks | 16 weeks after treatment | Percent of participants with peak eosinophil count \< 15 eosinophils/high power field (remission) in distal and proximal esophagus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Eosinophil Count at 16 Weeks | Baseline, 16 weeks after treatment | Mean change in peak eosinophil count from baseline |
| Change in Pediatric EoE Symptom Score at 16 Weeks | Baseline, 16 weeks after treatment | The PEESS V2.0 questionnaire captures EoE-specific symptoms (dysphagia, GERD, nausea/vomiting, and pain) as reported by parents. The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan Participants with eosinophilic esophagitis receive the Losartan daily
Losartan Potassium: The dose of study drug is dependent on body weight and tolerance but did not exceed 100 mg. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Losartan |
|---|---|
| Age, Continuous | 13.4 years STANDARD_DEVIATION 5.2 |
| Peak Eosinophil Count Distal Peak Eosinophil Counts | 108 eosinophils per high power field STANDARD_DEVIATION 86 |
| Peak Eosinophil Count Proximal Peak Eosinophil Counts | 40 eosinophils per high power field STANDARD_DEVIATION 37 |
| Pediatric EoE Symptom Score | 28 units on a scale STANDARD_DEVIATION 20 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Percent of Participants in Histologic Remission at 16 Weeks
Percent of participants with peak eosinophil count \< 15 eosinophils/high power field (remission) in distal and proximal esophagus
Time frame: 16 weeks after treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Losartan | Percent of Participants in Histologic Remission at 16 Weeks | Distal Remission | 17 percentage of participants |
| Losartan | Percent of Participants in Histologic Remission at 16 Weeks | Proximal Remission | 17 percentage of participants |
Secondary
Change in Peak Eosinophil Count at 16 Weeks
Mean change in peak eosinophil count from baseline
Time frame: Baseline, 16 weeks after treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Losartan | Change in Peak Eosinophil Count at 16 Weeks | Change in Proximal Peak Count | 3 eosinophils/high power field | Standard Deviation 62 |
| Losartan | Change in Peak Eosinophil Count at 16 Weeks | Change in Distal Peak Count | -43 eosinophils/high power field | Standard Deviation 107 |
Secondary
Change in Pediatric EoE Symptom Score at 16 Weeks
The PEESS V2.0 questionnaire captures EoE-specific symptoms (dysphagia, GERD, nausea/vomiting, and pain) as reported by parents. The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline.
Time frame: Baseline, 16 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan | Change in Pediatric EoE Symptom Score at 16 Weeks | -11 score on a scale | Standard Deviation 12 |