A Trial of Montelukast for Maintenance Therapy of Eosinophilic Esophagitis in Children
NCT ID: NCT01458418
Last Updated: 2020-10-30
Study Results
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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
TERMINATED
Clinical Phase
NA
Total Enrollment
4 participants
Study Classification
INTERVENTIONAL
Study Start Date
2011-12-31
Study Completion Date
2015-02-28
Brief Summary
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Eosinophilic Esophagitis (EE) is a condition where eosinophils (a cell that fights infection) travel to the esophagus (the tube through which food passes to the stomach). These cells do not belong there and can cause pain, soreness, difficulty swallowing and sometimes vomiting.
Ways to treat this condition include medicine, not eating some foods, and drinking a specific formula (like milk) without eating any other foods. Doing these things can help fight off EE but these problems can come back when treatment is stopped. If EE symptoms go on for a long time, it can lead to the esophagus becoming narrow and feeling tight when eating and swallowing and surgery may be needed to widen the narrowed area to relieve the sensation of tightening.
Montelukast is a medicine that fights off a type of chemical that can be a magnet for eosinophils. People usually take this medicine to help treat their asthma. It is not approved to treat EE. This medication is taken once a day.
The purpose of this study is to see if Montelukast, compared to placebo, will help reduce the number of eosinophils in children with EE and help stop the tightening of the esophagus.
Ways to treat this condition include medicine, not eating some foods, and drinking a specific formula (like milk) without eating any other foods. Doing these things can help fight off EE but these problems can come back when treatment is stopped. If EE symptoms go on for a long time, it can lead to the esophagus becoming narrow and feeling tight when eating and swallowing and surgery may be needed to widen the narrowed area to relieve the sensation of tightening.
Montelukast is a medicine that fights off a type of chemical that can be a magnet for eosinophils. People usually take this medicine to help treat their asthma. It is not approved to treat EE. This medication is taken once a day.
The purpose of this study is to see if Montelukast, compared to placebo, will help reduce the number of eosinophils in children with EE and help stop the tightening of the esophagus.
Detailed Description
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Eosinophilic esophagitis (EE) is a disease diagnosed using both clinical and pathologic results. Presentation varies among age groups with younger children suffering from vomiting, failure to thrive, or food refusal and adolescents suffering from dysphagia, odynophagia, or food impaction. It is more prevalent in males. EE is suggested when an upper endoscopy yields eosinophils greater than 15 per high power field (hpf) in both the middle and distal esophagus. Therapy for EE depends upon age and ability to be compliant. Three main categories of treatment are options for families, including the use of medicines, removal of the most allergenic foods, and the use of an elemental diet (formula) (1-2). Treatment can be different within the two main phases of therapy for EE, initial and maintenance therapy. Initial therapy occurs when the patient is first diagnosed and has eosinophils over 15 per hpf and can last for years if the patient does not respond to treatment. Maintenance therapy only occurs after the patient has responded to treatment with a reduction of his/her eosinophil counts below 5 per hpf. Typically, medicinal therapy with steroids (either oral prednisone or swallowed fluticasone) improves eosinophil counts but has a large side effect profile suggesting that steroids are not ideal for maintenance therapy. Dietary therapies are effective in both treatment phases but many patients find it difficult to remain compliant with food restriction for a prolonged length of time. Unfortunately, EE recurs upon withdrawal of oral therapy (3-7).
EE is believed to be an imbalance of the TH1/TH2 immune system and is more prevalent in patients with asthma and allergies (8-9). Some EE centers have started treating patients with targeted elimination diets and elemental diets and are having good success. Unfortunately, most families and in particular teenagers, are noncompliant with the dietary therapies. Formula for the elemental diet is not covered by most insurance and is very costly as well. Therefore, finding a drug that would keep a patient with EE in maintenance therapy and reduce both the long term consequences of steroids and potential for esophageal strictures would be ideal.
Many adults with EE present with dysphagia or food impactions and subsequently are found to have an esophageal stricture requiring multiple esophageal dilatations for treatment. Esophageal subepithelial fibrosis has been found in the adult literature in patients with EE. Chehade et al evaluated distal esophageal biopsy specimens in children with EE, eosinophilic gastroenteritis, gastroesophageal reflux disease, and controls for the presence of increased collagen deposition indicative of fibrosis. They found that fibrosis was present in 57% of patients with EE, of which 42% had symptoms of dysphagia and 80% had food impactions. The degree of fibrosis was not associated with eosinophil count but was associated with eosinophilic degranulation (10). Upon degranulation, eosinophils release major basic protein (MBP) and transforming growth factor (TGF-β). MBP changes smooth muscle contractility by blocking M2 muscarinic receptors therefore changing the motility of the esophagus. TGF-β is believed to cause an increase in the production of the extracellular matrix and smooth muscle hypertrophy and hyperplasia leading to esophageal thickening and fibrosis. TGF-β is a key growth factor that increases fibroblasts and subsequent fibrosis in the lung as well. Corticosteroids have been shown to reverse esophageal remodeling, but no large clinical trials have evaluated the treatment of esophageal fibrosis related to EE. To quote Aceves and Ackerman: "\[f\]ibrosis likely contributes to multiple clinical aspects of EE, including dysphagia symptoms, disease chronicity, and stricture formation." Fibrosis is measured in esophageal tissue by evaluating the amount of collagen that is deposited. Trichrome stains specifically for collagen (11).
Patients with EE have an abundance of inappropriate cells within the esophagus, including eosinophils and mast cells. A normal esophagus is devoid of eosinophils. Mast cells likely have an active role in the development of eosinophilic esophagitis; unfortunately the precise mechanism is unknown. Mast cells are found in the majority of vascularized tissues and are abundant in the gastrointestinal tract. They are located in the submucosa and lamina propria. Within the esophagus specifically, they are found in the mucosa and submucosa with rare expansion into muscularis layer. With severe eosinophilic inflammation, mast cells can be seen in the muscularis layer. Biopsies from patients with EE have demonstrated marked increase in mast cells in the mucosal layer of the esophagus. There has been correlation of mast cell number with degree of eosinophilia. Mast cells within the GI tract contain tryptase as well as other preformed mediators and can synthesize mediators that promote inflammation. Tryptase may activate eosinophils and therefore induce eosinophilic degranulation and cytokine secretion. Mast cells release chemokines and leukotrienes specific to eosinophil recruitment. Ultimately mast cell mediators worsen edema, create more inflammation, induce smooth muscle contractility and potentially affect tissue fibrosis. Therefore, active mast cells are proinflammatory, modify esophageal function, and encourage the development of strictures (12). Mast cells may be a key component in the propagation of the inflammatory state as well as of significant importance in the development of fibrosis. Evaluating tryptase levels could lead to a better understanding of the inflammatory process and ultimate problem of fibrosis.
Eosinophils and mast cells contain leukotrienes in abundance. Cysteinyl leukotrienes are inflammatory mediators derived from arachidonic acid. They are important in eosinophil attraction and migration, smooth muscle bronchoconstriction, vascular permeability, and mucus hypersecretion (13). Montelukast is a leukotriene receptor antagonist and blocks specifically the leukotriene D4 (LTD4) receptor. Attwood et al treated 8 patients with EE with Montelukast for which 6 reported complete subjective improvement and 5 remained asymptomatic on a maintenance regimen. Treatment with Montelukast did not change the density of eosinophils present in the esophagus however (14). Montelukast has been used in mouse models to decrease fibrosis occurring in both the liver and the lung. El-Swefy and Hassanen performed a randomized study in which they subjected mice to one of 4 groups, no bile duct ligation plus saline, no bile duct ligation plus montelukast, bile duct ligation plus montelukast and bile duct ligation plus saline. Bile duct ligation induced inflammation leading to cirrhosis and fibrosis. They found that bile duct ligation increased the amount of TGF-β, which correlated with the amount of fibrosis found. Of more import is that montelukast significantly reduced the amount of fibrosis as well as decreased the amount of TGF-β (15). Izumo, Kondo, and Nagai evaluated the use of montelukast in the prevention of pulmonary fibrosis after exposure to bleomycin. They found that mice given montelukast had significantly lower levels of TGF-β and fibrosis of the lung (16).
The investigator's research focus throughout fellowship included several retrospective studies in eosinophilic esophagitis. One of the investiagotor's studies evaluated the management of both initial and maintenance therapy for EE within our department. The investigator wanted to know what medicines the majority of pediatric gastroenterologists at the investigator's institution were using to treat EE and how often patients were being reevaluated by endoscopy. The investigator also wanted to evaluate the use of montelukast in the treatment of EE. The investigator reviewed 1500 charts of patients who had undergone upper endoscopy and had a result of "esophagitis." Patients were then selected by the presence of greater than or equal to 20 eosinophils per high power field in at least one biopsy location. Of the 1500 charts the investigator evaluated, only 88 patients fulfilled criteria for EE. The investigator discovered that there is not a consistent standard of care within their department for the initial and maintenance treatment of EE. Many different medicines are trialed initially and patients undergo esophageal biopsies at different time intervals, contrary to what is recommended. The primary group of 88 patients was then separated into 49 patients who reached maintenance therapy (defined by less than 5 eosinophils per high power field) and 39 patients who never experienced improvement in their eosinophil counts. Of the 49 who reached maintenance therapy, 30 patients were treated with montelukast and had follow up endoscopy. The investigator evaluated peak eosinophil counts pre and post treatment, and contrary to their hypothesis, those patients treated with 5mg of montelukast had lower post treatment eosinophil counts than those treated with higher doses (10 and 20mg). This raised the possibility that the packaging differences of the two main doses had an impact in treatment. The investigator considered the possibility that the lower dosage of montelukast is protective since 5mg tablets are chewable and would yield a topical effect on the esophagus whereas the 10mg tablets are swallowed, not chewed. In addition, the investigator evaluated how often EE recurred and discovered there was a high rate of histologic recurrence. Also interesting to the investigator was the lower recurrence rate in patients given 5mg of montelukast compared to 10mg and 20mg doses. These results were not expected and deserve further evaluation. If montelukast can prevent fibrosis through a topical effect, then its therapeutic potential is huge in the treatment of EE.
The investigator has developed a study that will investigate the use of montelukast in total vs placebo as well as allow them to look for dosing effects within montelukast in the treatment of eosinophilic esophagitis. The primary objective is to evaluate if montelukast will keep eosinophil counts low enough for the patient to remain in remission and if so, is there a particular dose of montelukast that will achieve this in a greater proportion. All patients will be maintained on a proton pump inhibitor (PPI) at baseline so that patients receiving placebo will still receive standard of care treatment. Many GI practitioners at this institution will place patients with EE on montelukast as part of standard of care treatment at varying doses without any good literature to support this use. The investigator's goal is to determine if montelukast is a valuable therapy in the treatment of EE. The investigator's study will also evaluate histological stains that may show an improvement with the use of montelukast, even if the eosinophil counts do not change, as the chemicals released by eosinophils and mast cells may be of primary import in the continuation of EE.
EE is believed to be an imbalance of the TH1/TH2 immune system and is more prevalent in patients with asthma and allergies (8-9). Some EE centers have started treating patients with targeted elimination diets and elemental diets and are having good success. Unfortunately, most families and in particular teenagers, are noncompliant with the dietary therapies. Formula for the elemental diet is not covered by most insurance and is very costly as well. Therefore, finding a drug that would keep a patient with EE in maintenance therapy and reduce both the long term consequences of steroids and potential for esophageal strictures would be ideal.
Many adults with EE present with dysphagia or food impactions and subsequently are found to have an esophageal stricture requiring multiple esophageal dilatations for treatment. Esophageal subepithelial fibrosis has been found in the adult literature in patients with EE. Chehade et al evaluated distal esophageal biopsy specimens in children with EE, eosinophilic gastroenteritis, gastroesophageal reflux disease, and controls for the presence of increased collagen deposition indicative of fibrosis. They found that fibrosis was present in 57% of patients with EE, of which 42% had symptoms of dysphagia and 80% had food impactions. The degree of fibrosis was not associated with eosinophil count but was associated with eosinophilic degranulation (10). Upon degranulation, eosinophils release major basic protein (MBP) and transforming growth factor (TGF-β). MBP changes smooth muscle contractility by blocking M2 muscarinic receptors therefore changing the motility of the esophagus. TGF-β is believed to cause an increase in the production of the extracellular matrix and smooth muscle hypertrophy and hyperplasia leading to esophageal thickening and fibrosis. TGF-β is a key growth factor that increases fibroblasts and subsequent fibrosis in the lung as well. Corticosteroids have been shown to reverse esophageal remodeling, but no large clinical trials have evaluated the treatment of esophageal fibrosis related to EE. To quote Aceves and Ackerman: "\[f\]ibrosis likely contributes to multiple clinical aspects of EE, including dysphagia symptoms, disease chronicity, and stricture formation." Fibrosis is measured in esophageal tissue by evaluating the amount of collagen that is deposited. Trichrome stains specifically for collagen (11).
Patients with EE have an abundance of inappropriate cells within the esophagus, including eosinophils and mast cells. A normal esophagus is devoid of eosinophils. Mast cells likely have an active role in the development of eosinophilic esophagitis; unfortunately the precise mechanism is unknown. Mast cells are found in the majority of vascularized tissues and are abundant in the gastrointestinal tract. They are located in the submucosa and lamina propria. Within the esophagus specifically, they are found in the mucosa and submucosa with rare expansion into muscularis layer. With severe eosinophilic inflammation, mast cells can be seen in the muscularis layer. Biopsies from patients with EE have demonstrated marked increase in mast cells in the mucosal layer of the esophagus. There has been correlation of mast cell number with degree of eosinophilia. Mast cells within the GI tract contain tryptase as well as other preformed mediators and can synthesize mediators that promote inflammation. Tryptase may activate eosinophils and therefore induce eosinophilic degranulation and cytokine secretion. Mast cells release chemokines and leukotrienes specific to eosinophil recruitment. Ultimately mast cell mediators worsen edema, create more inflammation, induce smooth muscle contractility and potentially affect tissue fibrosis. Therefore, active mast cells are proinflammatory, modify esophageal function, and encourage the development of strictures (12). Mast cells may be a key component in the propagation of the inflammatory state as well as of significant importance in the development of fibrosis. Evaluating tryptase levels could lead to a better understanding of the inflammatory process and ultimate problem of fibrosis.
Eosinophils and mast cells contain leukotrienes in abundance. Cysteinyl leukotrienes are inflammatory mediators derived from arachidonic acid. They are important in eosinophil attraction and migration, smooth muscle bronchoconstriction, vascular permeability, and mucus hypersecretion (13). Montelukast is a leukotriene receptor antagonist and blocks specifically the leukotriene D4 (LTD4) receptor. Attwood et al treated 8 patients with EE with Montelukast for which 6 reported complete subjective improvement and 5 remained asymptomatic on a maintenance regimen. Treatment with Montelukast did not change the density of eosinophils present in the esophagus however (14). Montelukast has been used in mouse models to decrease fibrosis occurring in both the liver and the lung. El-Swefy and Hassanen performed a randomized study in which they subjected mice to one of 4 groups, no bile duct ligation plus saline, no bile duct ligation plus montelukast, bile duct ligation plus montelukast and bile duct ligation plus saline. Bile duct ligation induced inflammation leading to cirrhosis and fibrosis. They found that bile duct ligation increased the amount of TGF-β, which correlated with the amount of fibrosis found. Of more import is that montelukast significantly reduced the amount of fibrosis as well as decreased the amount of TGF-β (15). Izumo, Kondo, and Nagai evaluated the use of montelukast in the prevention of pulmonary fibrosis after exposure to bleomycin. They found that mice given montelukast had significantly lower levels of TGF-β and fibrosis of the lung (16).
The investigator's research focus throughout fellowship included several retrospective studies in eosinophilic esophagitis. One of the investiagotor's studies evaluated the management of both initial and maintenance therapy for EE within our department. The investigator wanted to know what medicines the majority of pediatric gastroenterologists at the investigator's institution were using to treat EE and how often patients were being reevaluated by endoscopy. The investigator also wanted to evaluate the use of montelukast in the treatment of EE. The investigator reviewed 1500 charts of patients who had undergone upper endoscopy and had a result of "esophagitis." Patients were then selected by the presence of greater than or equal to 20 eosinophils per high power field in at least one biopsy location. Of the 1500 charts the investigator evaluated, only 88 patients fulfilled criteria for EE. The investigator discovered that there is not a consistent standard of care within their department for the initial and maintenance treatment of EE. Many different medicines are trialed initially and patients undergo esophageal biopsies at different time intervals, contrary to what is recommended. The primary group of 88 patients was then separated into 49 patients who reached maintenance therapy (defined by less than 5 eosinophils per high power field) and 39 patients who never experienced improvement in their eosinophil counts. Of the 49 who reached maintenance therapy, 30 patients were treated with montelukast and had follow up endoscopy. The investigator evaluated peak eosinophil counts pre and post treatment, and contrary to their hypothesis, those patients treated with 5mg of montelukast had lower post treatment eosinophil counts than those treated with higher doses (10 and 20mg). This raised the possibility that the packaging differences of the two main doses had an impact in treatment. The investigator considered the possibility that the lower dosage of montelukast is protective since 5mg tablets are chewable and would yield a topical effect on the esophagus whereas the 10mg tablets are swallowed, not chewed. In addition, the investigator evaluated how often EE recurred and discovered there was a high rate of histologic recurrence. Also interesting to the investigator was the lower recurrence rate in patients given 5mg of montelukast compared to 10mg and 20mg doses. These results were not expected and deserve further evaluation. If montelukast can prevent fibrosis through a topical effect, then its therapeutic potential is huge in the treatment of EE.
The investigator has developed a study that will investigate the use of montelukast in total vs placebo as well as allow them to look for dosing effects within montelukast in the treatment of eosinophilic esophagitis. The primary objective is to evaluate if montelukast will keep eosinophil counts low enough for the patient to remain in remission and if so, is there a particular dose of montelukast that will achieve this in a greater proportion. All patients will be maintained on a proton pump inhibitor (PPI) at baseline so that patients receiving placebo will still receive standard of care treatment. Many GI practitioners at this institution will place patients with EE on montelukast as part of standard of care treatment at varying doses without any good literature to support this use. The investigator's goal is to determine if montelukast is a valuable therapy in the treatment of EE. The investigator's study will also evaluate histological stains that may show an improvement with the use of montelukast, even if the eosinophil counts do not change, as the chemicals released by eosinophils and mast cells may be of primary import in the continuation of EE.
Conditions
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Eosinophilic Esophagitis
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Study Groups
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Montelukast 10 mg/day
Subjects will receive two 5mg tablets of Montelukast/day.
Group Type
EXPERIMENTAL
Montelukast
Intervention Type
DRUG
Those in Montelukast 10mg/day group will receive two 5mg tablets of Montelukast.
Montelukast 5mg/day
Subjects will receive one 5mg tablet of montelukast and 1 placebo tablet per day.
Group Type
EXPERIMENTAL
5 mg Montelukast
Intervention Type
DRUG
Subject will receive one 5mg tablet of Montelukast and one placebo tablet per day.
placebo
Subjects will receive two placebo tablets per day.
Group Type
PLACEBO_COMPARATOR
placebo
Intervention Type
OTHER
Those in the placebo group will receive 2 placebo tablets per day. Those in the Montelukast 5mg/day will receive 1 placebo tablet per day.
Interventions
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Montelukast
Those in Montelukast 10mg/day group will receive two 5mg tablets of Montelukast.
Intervention Type
DRUG
placebo
Those in the placebo group will receive 2 placebo tablets per day. Those in the Montelukast 5mg/day will receive 1 placebo tablet per day.
Intervention Type
OTHER
5 mg Montelukast
Subject will receive one 5mg tablet of Montelukast and one placebo tablet per day.
Intervention Type
DRUG
Other Intervention Names
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Singulair
Singulair
Eligibility Criteria
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Inclusion Criteria
* Males and females aged 2-17
* Presence of more than 15 eosinophils per hpf on original endoscopy and less than 5 eosinophils/hpf on the most recent endoscopy
* Concurrent PPI for 1 month at 1-2mg/kg/dose prior to endoscopy or have a negative pH study
* English speaking
* Ability to undergo a follow up endoscopy between 12 and 13 weeks after the start of the study
* Procurement of written informed consent signed by the subject's legal guardian and study investigator (s) and subject assent.
* Presence of more than 15 eosinophils per hpf on original endoscopy and less than 5 eosinophils/hpf on the most recent endoscopy
* Concurrent PPI for 1 month at 1-2mg/kg/dose prior to endoscopy or have a negative pH study
* English speaking
* Ability to undergo a follow up endoscopy between 12 and 13 weeks after the start of the study
* Procurement of written informed consent signed by the subject's legal guardian and study investigator (s) and subject assent.
Exclusion Criteria
* Subjects with eosinophils in stomach and duodenum on original endoscopy.
* Subjects requiring oral prednisone within 1 month of current endoscopy.
* Subjects with diagnosis of other co-morbid diseases such as heart disease, renal disease, autoimmune disease, an immunodeficiency, diabetes, phenylketonuria, or thyroid disease.
* Subjects using Montelukast within one month of current endoscopy
* Subjects with concurrent use of phenobarbital or rifampin
* Subjects requiring oral prednisone within 1 month of current endoscopy.
* Subjects with diagnosis of other co-morbid diseases such as heart disease, renal disease, autoimmune disease, an immunodeficiency, diabetes, phenylketonuria, or thyroid disease.
* Subjects using Montelukast within one month of current endoscopy
* Subjects with concurrent use of phenobarbital or rifampin
Minimum Eligible Age
2 Years
Maximum Eligible Age
17 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Children's Mercy Hospital Kansas City
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Stephanie Page, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Mercy Hospital Kansas City
Locations
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Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Site Status
Countries
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United States
References
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Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME; First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007 Oct;133(4):1342-63. doi: 10.1053/j.gastro.2007.08.017. Epub 2007 Aug 8.
Reference Type
BACKGROUND
Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology. 2009 Oct;137(4):1238-49. doi: 10.1053/j.gastro.2009.07.007. Epub 2009 Aug 15.
Reference Type
BACKGROUND
Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, Akers R, Cohen MB, Collins MH, Assa'ad AH, Aceves SS, Putnam PE, Rothenberg ME. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006 Nov;131(5):1381-91. doi: 10.1053/j.gastro.2006.08.033. Epub 2006 Aug 16.
Reference Type
BACKGROUND
Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, Lim JD, Steiner SJ, Gupta SK. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008 Feb;6(2):165-73. doi: 10.1016/j.cgh.2007.11.008.
Reference Type
BACKGROUND
Dohil R, Newbury R, Fox L, Bastian J, Aceves S. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010 Aug;139(2):418-29. doi: 10.1053/j.gastro.2010.05.001. Epub 2010 May 7.
Reference Type
BACKGROUND
Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003 Apr;98(4):777-82. doi: 10.1111/j.1572-0241.2003.07390.x.
Reference Type
BACKGROUND
Assa'ad AH, Putnam PE, Collins MH, Akers RM, Jameson SC, Kirby CL, Buckmeier BK, Bullock JZ, Collier AR, Konikoff MR, Noel RJ, Guajardo JR, Rothenberg ME. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol. 2007 Mar;119(3):731-8. doi: 10.1016/j.jaci.2006.10.044. Epub 2007 Jan 25.
Reference Type
BACKGROUND
Blanchard C, Wang N, Rothenberg ME. Eosinophilic esophagitis: pathogenesis, genetics, and therapy. J Allergy Clin Immunol. 2006 Nov;118(5):1054-9. doi: 10.1016/j.jaci.2006.07.038. Epub 2006 Sep 18.
Reference Type
BACKGROUND
Blanchard C, Rothenberg ME. Basic pathogenesis of eosinophilic esophagitis. Gastrointest Endosc Clin N Am. 2008 Jan;18(1):133-43; x. doi: 10.1016/j.giec.2007.09.016.
Reference Type
BACKGROUND
Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal subepithelial fibrosis in children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007 Sep;45(3):319-28. doi: 10.1097/MPG.0b013e31806ab384.
Reference Type
BACKGROUND
Aceves SS, Ackerman SJ. Relationships between eosinophilic inflammation, tissue remodeling, and fibrosis in eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009 Feb;29(1):197-211, xiii-xiv. doi: 10.1016/j.iac.2008.10.003.
Reference Type
BACKGROUND
Wershil BK. Exploring the role of mast cells in eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009 Feb;29(1):189-95, xiii. doi: 10.1016/j.iac.2008.09.006.
Reference Type
BACKGROUND
Lucendo AJ, Bellon T, Lucendo B. The role of mast cells in eosinophilic esophagitis. Pediatr Allergy Immunol. 2009 Sep;20(6):512-8. doi: 10.1111/j.1399-3038.2008.00798.x. Epub 2008 Aug 4.
Reference Type
BACKGROUND
Attwood SE, Lewis CJ, Bronder CS, Morris CD, Armstrong GR, Whittam J. Eosinophilic oesophagitis: a novel treatment using Montelukast. Gut. 2003 Feb;52(2):181-5. doi: 10.1136/gut.52.2.181.
Reference Type
BACKGROUND
El-Swefy S, Hassanen SI. Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats. Ann Hepatol. 2009 Jan-Mar;8(1):41-9.
Reference Type
BACKGROUND
Izumo T, Kondo M, Nagai A. Cysteinyl-leukotriene 1 receptor antagonist attenuates bleomycin-induced pulmonary fibrosis in mice. Life Sci. 2007 Apr 24;80(20):1882-6. doi: 10.1016/j.lfs.2007.02.038. Epub 2007 Mar 12.
Reference Type
BACKGROUND
Montagna NA, de Oliveira ML, Mandarim-de-Lacerda CA, Chimelli L. Leprosy: contribution of mast cells to epineurial collagenization. Clin Neuropathol. 2005 Nov-Dec;24(6):284-90.
Reference Type
BACKGROUND
Other Identifiers
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CMH 11 01-007
Identifier Type: -
Identifier Source: org_study_id