Clinical trial NCT03029091: An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)
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
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Office of Rare Diseases (ORD)
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2017-01-24
Enrollment: 15
Sex: ALL
Minimum age (years): 5
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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 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.

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.

Eligibility 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)

Primary outcomes:
measure: Change From Baseline in Peak Eosinophil Count
timeFrame: Baseline, 16 weeks
measure: Number of Serious and Grade 3 or Higher Adverse Events
timeFrame: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)
Secondary outcomes:
measure: Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks
timeFrame: 16 weeks
measure: Change From Baseline in Total Histology Scoring System
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in Total Endoscopic Reference Score
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in PEESS V2.0
timeFrame: Baseline,16 weeks
measure: Change From Baseline in PedsQL EoE
timeFrame: Baseline, 16 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Marc E Rothenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: