Eosinophilic EsophagitisPhase 2NCT03029091
An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)
A Phase 2 study testing Losartan Potassium in people with Eosinophilic Esophagitis, run by Children's Hospital Medical Center, Cincinnati at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 25 years
- Conditions the study is for
- Eosinophilic Esophagitis
- What is being tested?
- Losartan Potassium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 May 2017to 22 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
- Of non-childbearing potential (pre-menarchal or surgically sterile with documentation). OR
- Have a negative urine pregnancy test at screening and at each monthly study visit.
Who cannot join
- 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).
Show all 18Show fewer
- 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 locations and contacts
3 sites in 1 country.
United States3 sites
Northwestern University
Chicago, Illinois, 60208
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of California, San Diego
La Jolla, California, 92093
About this study
Official title: A Preliminary Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder
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.
Read the 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.
- Conditions
- Eosinophilic Esophagitis
- Being tested
- Losartan Potassium
- Medical subject headings
- Eosinophilic Esophagitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan PotassiumDrug
Also called Losartan
Losartan potassium
| Study group | Role | What they receive |
|---|---|---|
| EoE +/- CTD | Experimental | 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 Receives: Drug: Losartan Potassium |
| EoE + CTD | Experimental | 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 Receives: Drug: Losartan Potassium |
| EoE - CTD | Experimental | 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 Receives: Drug: Losartan Potassium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Peak Eosinophil Count
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.
Measured: Baseline, 16 weeks
Number of Serious and Grade 3 or Higher Adverse Events
The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20
Measured: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)
Secondary outcomes (5)
Percent of Participants in Complete and Partial Histologic Remission at 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.
Measured: 16 weeks
Change From Baseline in Total Histology Scoring System
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.
Measured: Baseline, 16 weeks
Change From Baseline in Total Endoscopic Reference Score
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.
Measured: Baseline, 16 weeks
Change From Baseline in PEESS V2.0
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.
Measured: Baseline,16 weeks
Change From Baseline in PedsQL EoE
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.
Measured: Baseline, 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start23 May 2017
- Primary completion22 Jul 2019
- Study completion22 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Eosinophilic EsophagitisStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This study is an open-label study which means that all participants receive the study medicine.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- 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 Sciences (NCATS)
- Responsible party
- Sponsor
- Investigators
- Marc E Rothenberg, MD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029091
- Sponsor's protocol ID
- 2015-9021
- Other IDs
- U54AI117804
- Status last verified
- Jul 2020
- First submitted
- 20 Jan 2017
- Last updated
- 9 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Preliminary Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) With or Without a Connective Tissue Disorder
- ClinicalTrials.gov ID
- NCT03029091
- Acronym / sponsor ID
- 2015-9021
- Conditions
- Eosinophilic Esophagitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- 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 Sciences (NCATS)
- Study start
- 23 May 2017 (actual)
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Aug 2019 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Posted 10 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This study is an open-label study which means that all participants receive the study medicine.
| Arm | Type | Receives |
|---|---|---|
| EoE +/- CTD | Experimental | Drug: Losartan PotassiumParticipants 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 |
| EoE + CTD | Experimental | Drug: Losartan PotassiumParticipants 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 |
| EoE - CTD | Experimental | Drug: Losartan PotassiumParticipants 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 |
Who may qualify
- Ages
- 5 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losartan PotassiumAlso: LosartanLosartan potassium | Drug | EoE + CTD, EoE +/- CTD, EoE - CTD |
Primary outcome
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.
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
5 secondary outcomes
Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks
Time frame: 16 weeks
Change From Baseline in Total Histology Scoring System
Time frame: Baseline, 16 weeks
Change From Baseline in Total Endoscopic Reference Score
Time frame: Baseline, 16 weeks
Change From Baseline in PEESS V2.0
Time frame: Baseline,16 weeks
Change From Baseline in PedsQL EoE
Time frame: Baseline, 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Study information on the Consortium for Eosinophilic Gastrointestinal Disorders (CEGIR) websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc E Rothenberg, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan Potassium in people with Eosinophilic Esophagitis, run by Children's Hospital Medical Center, Cincinnati at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Peak Eosinophil Count (time frame: Baseline, 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.