Clinical trial NCT01808196: Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
Official title: A Preliminary, Open-label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Esophagitis
Connective Tissue Disorders
Keywords: Eosinophilic Esophagitis
Connective Tissue Disorders
Drug trial
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2013-03-11
Enrollment: 6
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is an open-label study which means that all participants receive the study medicine
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent of Participants in Histologic Remission at 16 Weeks
timeFrame: 16 weeks after treatment
Secondary outcomes:
measure: Change in Peak Eosinophil Count at 16 Weeks
timeFrame: Baseline, 16 weeks after treatment
measure: Change in Pediatric EoE Symptom Score at 16 Weeks
timeFrame: Baseline, 16 weeks after treatment
Other outcomes:
Locations:
city: Mason
country: United States
facility: Kara Kliewer
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: J. Pablo Abonia, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Marc E Rothenberg, M.D., Ph.D.
role: STUDY_DIRECTOR
References: