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| ID | Type | Description | Link |
|---|---|---|---|
| U54AI117804 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| Office of Rare Diseases (ORD) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan Potassium | Drug | Losartan potassium |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 16 weeks |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc E Rothenberg, MD, PhD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego | La Jolla | California | 92093 | United States | ||
| Northwestern University |
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| Label | URL |
|---|---|
| Study information on the Consortium for Eosinophilic Gastrointestinal Disorders (CEGIR) website | View source |
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17 participants screened, 2 excluded (2 met exclusion criteria), and 15 initiated the intervention
Participants were recruited from eosinophilic esophagitis specialty clinics (3 sites) in the USA between May 2017 and April 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | EoE + CTD | Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan |
| FG001 | EoE - CTD | Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | EoE + CTD | Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan |
| BG001 | EoE - CTD | Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Per protocol population (protocol violation excluded from data analysis) | Posted | Mean | 95% Confidence Interval | eosinophils per high power field | Baseline, 16 weeks |
|
From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EoE +/- CTD | Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marc E. Rothenberg, MD, PhD | Cincinnati Children's Hospital Medical Center | 513 636-7177 | marc.rothenberg@cchmc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 11, 2019 | Jul 14, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jun 25, 2018 | Jul 14, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D057765 | Eosinophilic Esophagitis |
| ID | Term |
|---|---|
| D004941 | Esophagitis |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| National Center for Advancing Translational Sciences (NCATS) |
| NIH |
This study is an open-label study which means that all participants receive the study medicine.
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| 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. | 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. | 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. | 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. | Baseline, 16 weeks |
| Chicago |
| Illinois |
| 60208 |
| United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan |
| OG002 | EoE - CTD | Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan |
|
|
| Primary | 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 | Intent to treat analysis including participants enrolled in the study | Posted | Number | events | 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up) |
|
|
|
| Secondary | 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. | Per protocol population (protocol violation excluded from data analysis) | Posted | Number | 95% Confidence Interval | percentage of subjects | 16 weeks |
|
|
|
| Secondary | 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. | Per protocol population (protocol violation excluded from data analysis). | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, 16 weeks |
|
|
|
| Secondary | 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. | Per protocol population (protocol violation excluded from data analysis). | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, 16 weeks |
|
|
|
| Secondary | 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. | Per protocol population (protocol violation excluded from data analysis) | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline,16 weeks |
|
|
|
| Secondary | 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. | Per protocol population (protocol violation excluded from data analysis) | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline, 16 weeks |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 12 |
| 15 |
| EG001 | EoE + CTD | Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan | 0 | 8 | 0 | 8 | 7 | 8 |
| EG002 | EoE - CTD | Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan | 0 | 7 | 0 | 7 | 5 | 7 |
| Conjunctivitis | Eye disorders | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Upper Respiratory Infection | Infections and infestations | Non-systematic Assessment |
|
| Fever | Infections and infestations | Non-systematic Assessment |
|
| Rhinitis Infective | Infections and infestations | Non-systematic Assessment |
|
| Common Cold | General disorders | Non-systematic Assessment |
|
| Creatinine increased | Investigations | Non-systematic Assessment |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Vasovagal reaction | Nervous system disorders | Non-systematic Assessment |
|
| Testicular pain | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Lightheaded | Social circumstances | Non-systematic Assessment |
|
| Transient Dizziness | General disorders | Non-systematic Assessment |
|
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| D005759 |
| Gastroenteritis |
| D004802 | Eosinophilia |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
|
|
|
|
| Change - PEESS Total Score |
|
|
|