Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01808196
First received: January 30, 2013
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Eosinophilic Esophagitis
Connective Tissue Disorders
Drug: Losartan Potassium
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Preliminary, Open-label Trial of Losartan Potassium Versus Placebo in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder.

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Number of participants with reduction of esophageal eosinophils [ Time Frame: up to five years ] [ Designated as safety issue: No ]

    Tissue samples will be obtained from the esophagus from participants to determine the effects of losartan compared to placebo on the reduction of esophageal eosinophils in participants with eosinophilic esophagitis with or without a connective tissue disorder. It is planned to evaluate the reduction as follows:

    1. % of participants with reduction of eosinophil count to =<1/hpf
    2. % of participants with reduction of eosinophil count to less than 15
    3. Average reduction in eosinophil count
    4. Comparison across groups with and without a connective tissue disorder

  • Number of participants with reduction of esophageal eosinophils [ Time Frame: up to five years ] [ Designated as safety issue: No ]

    Tissue samples will be obtained from the esophagus from participants to determine the effects of losartan compared to placebo on the reduction of esophageal eosinophils in participants with eosinophilic esophagitis with or without a connective tissue disorder. It is planned to evaluate the reduction as follows:

    1. % of participants with reduction of eosinophil count to =<1hpf
    2. % of participants with reduction of eosinophil count to less than 15
    3. Average reduction in eosinophil count
    4. Comparison across groups with and without a connective tissue disorder


Secondary Outcome Measures:
  • Number of participants with reduction in levels of the transforming growth factor beta protein. [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    Blood and tissue samples will be obtained from participants throughout the study to evaluate losartan on the reduction in levels of transforming growth factor beta (TGF-β pg/mL) in the blood and esophagus.

  • Number of participants that experience normalization of the EoE transcriptome [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    Blood and tissue samples will be obtained throughout the trial to investigate the number of participants that experience a normalization of the EoE transcriptome, mRNA expression fold difference <2 compared to normal controls in participants with EoE with or without a connective tissue disorder

  • Number of participants that have an improved score utilizing the Patient Reported Outcome questionnaires to assess for clinical symptom response. [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    To evaluate the effect of losartan by utilizing the Patient Reported Outcome questionnaires (metric scoring algorithm) to assess for clinical symptom response.

  • Number of participants that have an improved score on the histology scoring system. [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    To evaluate the effect of losartan by a study staff member pathologist scoring the tissue samples by utilizing the histology scoring system. This scoring system was created to express the severity and extent of abnormalities in the gastrointestinal tract that often accompany eosinophilic inflammation.

  • To determine the safety of Losartan [ Time Frame: up to five years ] [ Designated as safety issue: Yes ]
    To determine the safety of losartan by the absences of adverse events will be recorded in participants with Eosinophilic Esophagitis with or without a connective tissue disorder.


Estimated Enrollment: 15
Study Start Date: April 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EoE Only
Approximately 10 participants with EoE without a CTD will be enrolled, all of whom will receive the Losartan intervention.
Drug: Losartan Potassium
The medication dosage for Losartan will change throughout this study slowly increasing to a larger amount. You will start the study drug at a low dose. It will be increased at Visit 3/Week 4, unless you have certain side effects. The dose of study drug will be increased depending on your weight and how well you tolerate each dose and will not exceed 100mg of study drug. It may be increased or decreased during the study if there are any side effects.
Other Name: Angiotensin II Receptor Antagonists
Experimental: EoE and CTD
Approximately 5 participants with EoE and CTD will be enrolled, all of whom will receive the Losartan intervention.
Drug: Losartan Potassium
The medication dosage for Losartan will change throughout this study slowly increasing to a larger amount. You will start the study drug at a low dose. It will be increased at Visit 3/Week 4, unless you have certain side effects. The dose of study drug will be increased depending on your weight and how well you tolerate each dose and will not exceed 100mg of study drug. It may be increased or decreased during the study if there are any side effects.
Other Name: Angiotensin II Receptor Antagonists

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

Ages Eligible for Study:   5 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01808196

Contacts
Contact: Melody Hess, MS 513-636-5540 melody.hess@cchmc.org

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Tommie Grotjan, B.S.    513-803-1655    tommie.grotjan@cchmc.org   
Principal Investigator: Pablo Abonia, M.D.         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: J. Pablo Abonia, M.D. Children's Hospital Medical Center, Cincinnati
Study Director: Marc E Rothenberg, M.D., Ph.D. Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01808196     History of Changes
Other Study ID Numbers: 2012-0106
Study First Received: January 30, 2013
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Eosinophilic Esophagitis
Connective Tissue Disorders
Drug trial

Additional relevant MeSH terms:
Connective Tissue Diseases
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Angiotensin II
Losartan
Angiotensin Receptor Antagonists
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014