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

Cincinnati Children's Hospital Medical Center

Status and phase: Completed; Phase 2

Conditions: Eosinophilic Esophagitis

Treatments: Drug: Losartan Potassium

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03029091

U54AI117804 (U.S. NIH Grant/Contract)

2015-9021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 5 to 25 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 3 patient groups

EoE +/- CTD

Experimental group

Description:

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

Treatment:

Drug: Losartan Potassium

EoE + CTD

Experimental group

Description:

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

Treatment:

Drug: Losartan Potassium

EoE - CTD

Experimental group

Description:

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

Treatment:

Drug: Losartan Potassium