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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01808196
Recruitment Status : Unknown
Verified January 2018 by Children's Hospital Medical Center, Cincinnati.
Recruitment status was:  Active, not recruiting
First Posted : March 11, 2013
Last Update Posted : January 29, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE January 30, 2013
First Posted Date  ICMJE March 11, 2013
Last Update Posted Date January 29, 2018
Study Start Date  ICMJE April 2013
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2013)
  • Number of participants with reduction of esophageal eosinophils [ Time Frame: up to five years ]
    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 ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
Number of participants with reduction of esophageal eosinophils [ Time Frame: up to five years ]
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 0 in placebo versus losartan treated
  2. % of participants with reduction of eosinophil count to less than 15 in placebo versus losartan treated
  3. Average reduction in eosinophil count in placebo versus losartan treated
  4. Comparison across groups with and without a connective tissue disorder
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2013)
  • Number of participants with reduction in levels of the transforming growth factor beta protein. [ Time Frame: up to five years ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
  • Number of participants with reduction in levels of the transforming growth factor beta protein. [ Time Frame: up to five years ]
    Blood and tissue samples will be obtained from participants throughout the study to evaluate losartan versus a placebo on the reduction in levels of transforming growth factor beta (TGF-β pg/mL) in the blood and esophagus. Comparisons will be made between the placebo and losartan treated groups.
  • Number of participants that experience normalization of the EoE transcriptome [ Time Frame: up to five years ]
    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 ]
    To evaluate the effect of losartan versus a placebo by utilizing the Patient Reported Outcome questionnaires (metric scoring algorithm) to assess for clinical symptom response. Comparisons will be made between the placebo and losartan treated groups.
  • Number of participants that have an improved score on the histology scoring system. [ Time Frame: up to five years ]
    To evaluate the effect of losartan versus placebo 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. Comparisons will be made between the placebo and losartan treated groups.
  • To determine the safety of Losartan versus placebo [ Time Frame: up to five years ]
    To determine the safety of losartan versus placebo by the absences of adverse events will be recorded in participants with Eosinophilic Esophagitis with or without a connective tissue disorder.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
Official Title  ICMJE A Preliminary, Open-label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Eosinophilic Esophagitis
  • Connective Tissue Disorders
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: EoE Only
    Approximately 10 participants with EoE without a CTD will be enrolled, all of whom will receive the Losartan intervention.
    Intervention: Drug: Losartan Potassium
  • Experimental: EoE and CTD
    Approximately 5 participants with EoE and CTD will be enrolled, all of whom will receive the Losartan intervention.
    Intervention: Drug: Losartan Potassium
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: April 13, 2016)
6
Original Estimated Enrollment  ICMJE
 (submitted: March 7, 2013)
44
Estimated Study Completion Date  ICMJE August 2018
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01808196
Other Study ID Numbers  ICMJE 2012-0106
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP