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An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)

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: NCT03029091
Recruitment Status : Completed
First Posted : January 24, 2017
Results First Posted : August 10, 2020
Last Update Posted : September 9, 2020
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
The purpose of this study is to test the safety and effectiveness of Losartan potassium in subjects with eosinophilic esophagitis (EoE) including those with a connective tissue disorder (CTD) and those without a CTD.

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: Losartan Potassium Phase 2

Detailed Description:

The purpose of this research study is to test the safety and effects (good and bad) of Losartan potassium on participants with eosinophilic esophagitis (EoE). If a participant has a connective tissue disorder (CTD) the researchers want to see what effects (good or bad) Losartan has on EoE.

EoE is an inflammatory disease of the esophagus that is typically triggered by exposure to food. Connective tissue disorders (CTDs) are disorders that affect the connective tissues in the body such as tendons and ligaments.

A protein called transforming growth factor (TGF)-beta is associated with both EoE and CTD. Losartan may decrease the amount of TGF-beta and therefore help EoE and CTD.

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. This medication has not been studied in people with EoE.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is an open-label study which means that all participants receive the study medicine.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Preliminary Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder
Actual Study Start Date : May 23, 2017
Actual Primary Completion Date : July 22, 2019
Actual Study Completion Date : August 22, 2019


Arm Intervention/treatment
Experimental: EoE +/- CTD
Participants with EoE with and without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
Drug: Losartan Potassium
Losartan potassium
Other Name: Losartan

Experimental: EoE + CTD
Participants with EoE with CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
Drug: Losartan Potassium
Losartan potassium
Other Name: Losartan

Experimental: EoE - CTD
Participants with EoE without CTD receive Losartan Potassium, 0.7 - 0.9 mg/kg (titration)/1.0 - 1.4 mg/kg (maintenance) daily for 16 weeks
Drug: Losartan Potassium
Losartan potassium
Other Name: Losartan




Primary Outcome Measures :
  1. Change From Baseline in Peak Eosinophil Count [ Time Frame: Baseline, 16 weeks ]
    Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.

  2. Number of Serious and Grade 3 or Higher Adverse Events [ Time Frame: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up) ]
    The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20


Secondary Outcome Measures :
  1. Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks [ Time Frame: 16 weeks ]
    Percent of participants in complete and partial histologic remission. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.

  2. Change From Baseline in Total Histology Scoring System [ Time Frame: Baseline, 16 weeks ]
    The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.

  3. Change From Baseline in Total Endoscopic Reference Score [ Time Frame: Baseline, 16 weeks ]
    The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.

  4. Change From Baseline in PEESS V2.0 [ Time Frame: Baseline,16 weeks ]
    The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). 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 as completed by parent proxy.

  5. Change From Baseline in PedsQL EoE [ Time Frame: Baseline, 16 weeks ]
    The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent/assent
  • Confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)
  • Does or does not have diagnosis of a connective tissue disorder (CTD)
  • Has been on a high dose of proton pump inhibitor (PPI) for at least 8 weeks prior to a diagnostic endoscopy of EoE without histologic resolution (i.e., ≥ 15 eosinophils/HPF).
  • Maintain the same diet, swallowed steroid and PPI therapies throughout the duration of the study
  • Female participants must be either:

    1. Of non-childbearing potential (pre-menarchal or surgically sterile with documentation). OR
    2. Have a negative urine pregnancy test at screening and at each monthly study visit.

Exclusion Criteria:

  • Any past or planned cardiac surgery.
  • An aortic root Z-score ≥ 3.0 on a previous echocardiogram.
  • Intolerance to Losartan
  • A mean blood pressure measurement (both systolic and diastolic) at screening that is below the 2nd percentile for his/her age
  • Renal dysfunction
  • Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic syndrome, Churg Strauss vasculitis, eosinophilic granuloma, or a parasitic infection).
  • A diagnosis of hepatic insufficiency (e.g., liver failure, history of liver transplantation or persistent liver transaminase elevation).
  • A history of abnormal gastric or duodenal biopsy or documented gastrointestinal 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 (EGIDs).
  • Use of anti-immunoglobulin (Ig)E monoclonal antibody (mAb), anti-tumor necrosis factor (TNF) mAb, anti-IL-5 agents, or anti-IL-13 within 6 months prior to study entry
  • Use of methotrexate, cyclosporine, interferon α, or other systemic immunosuppressive or immunomodulating agents within 3 months prior to the screening visit.
  • A stricture during endoscopy procedure that prevents passage of the endoscope
  • Taking or is planning to take an angiotensin receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), beta blocker (BB), or calcium-channel blocker therapy at the screening visit or at any time during the study or has been taking any of these medications for 3 months prior to the screening visit.
  • Taking or planning to take hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, rifampin, or fluconazole.
  • Taking or planning to take potassium supplements or salt substitutes containing potassium.
  • A female participant who is pregnant or nursing or, if of childbearing potential, is not using a medically accepted, effective method of birth control (e.g., condom, oral/injectable/subcutaneous contraceptive, intrauterine device, or sexual abstinence).
  • Participated/participating in any investigative drug or device study within 30 days prior to study entry.
  • Participated/participating in any investigative biologics study within 3 months prior to study entry.
  • Unable to be confirmed, active EoE (at Screening or within 12 weeks prior to enrollment)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03029091


Locations
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United States, California
University of California, San Diego
La Jolla, California, United States, 92093
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60208
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Science (NCATS)
Investigators
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Principal Investigator: Marc E Rothenberg, MD, PhD Children's Hospital Medical Center, Cincinnati
  Study Documents (Full-Text)

Documents provided by Children's Hospital Medical Center, Cincinnati:
Statistical Analysis Plan  [PDF] December 11, 2019
Study Protocol  [PDF] June 25, 2018

Additional Information:
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03029091    
Other Study ID Numbers: 2015-9021
U54AI117804 ( U.S. NIH Grant/Contract )
First Posted: January 24, 2017    Key Record Dates
Results First Posted: August 10, 2020
Last Update Posted: September 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action