{"protocolSection":{"identificationModule":{"nctId":"NCT01479829","orgStudyIdInfo":{"id":"203368"},"organization":{"fullName":"Loyola University","class":"OTHER"},"briefTitle":"Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression","officialTitle":"Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression: Role of Inflammation and Kynurenine Pathway Biomarkers"},"statusModule":{"statusVerifiedDate":"2024-04","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2011-03-23","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2017-12-28","type":"ACTUAL"},"completionDateStruct":{"date":"2018-01-24","type":"ACTUAL"},"studyFirstSubmitDate":"2011-09-22","studyFirstSubmitQcDate":"2011-11-22","studyFirstPostDateStruct":{"date":"2011-11-24","type":"ESTIMATED"},"resultsFirstSubmitDate":"2024-03-13","resultsFirstSubmitQcDate":"2024-03-13","resultsFirstPostDateStruct":{"date":"2024-04-09","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-04-23","lastUpdatePostDateStruct":{"date":"2024-04-29","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Angelos Halaris","investigatorTitle":"Professor","investigatorAffiliation":"Loyola University"},"leadSponsor":{"name":"Loyola University","class":"OTHER"},"collaborators":[{"name":"Stanley Medical Research Institute","class":"OTHER"}]},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"This project will attempt to enhance and augment the antidepressant efficacy of a commonly used antidepressant in poorly responding bipolar depressed patients.","detailedDescription":"This is a placebo-controlled study of patients with bipolar I disorder (BPD) utilizing a well-known antidepressant, escitalopram (ESC), in combination with the anti-inflammatory agent, celecoxib (CBX). The investigators hypothesize that combination treatment will lead to a qualitatively and quantitatively augmented response and will result in greater numbers of remitters compared to ESC monotherapy."},"conditionsModule":{"conditions":["Bipolar Depression"],"keywords":["Bipolar depression","Celecoxib","Escitalopram","Inflammation"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":100,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Intervention cohort","type":"EXPERIMENTAL","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily.","interventionNames":["Drug: Escitalopram","Drug: Celecoxib"]},{"label":"Control cohort","type":"PLACEBO_COMPARATOR","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily.","interventionNames":["Drug: Escitalopram","Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Escitalopram","description":"Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI)","armGroupLabels":["Control cohort","Intervention cohort"],"otherNames":["Lexapro"]},{"type":"DRUG","name":"Celecoxib","description":"Celecoxib is a nonsteroidal anti-inflammatory drug","armGroupLabels":["Intervention cohort"],"otherNames":["Celebrex"]},{"type":"DRUG","name":"Placebo","description":"Placebo is a manufactured capsule with no active ingredient","armGroupLabels":["Control cohort"],"otherNames":["Inactive drug"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Response to Treatment","description":"Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, response to treatment is defined as a reduction in the HDRS-17 score of at least 50% after 8 weeks of treatment.","timeFrame":"8 weeks"},{"measure":"Disease Remission","description":"Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, diisease remission is defined as an HDRS-17 score less than 8 points after 8 weeks of treatment.","timeFrame":"8 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Ages 21 - 65 years old at time of screening visit. Both genders and any race will be accepted.\n* Diagnosis of BPD I or II without significant co-morbid secondary medical or psychiatric diagnoses; no substance abuse or dependence during preceding 12 months\n* A minimum score of 18 on the first 17 items of the 21-item Hamilton Depression Scale\n* Willingness to washout for a reasonable time (depending on the substance) from: Vitamin E and fish oils (\\>600 IU/day), non-aspirin NSAIDs or aspirin (\\>81 mg/day, H2 receptor antagonists, Ginko biloba, caffeine on morning of blood drawing, and to institute lights-out at 23:00 hours on the nights before blood drawings\n\nExclusion Criteria:\n\n* Any abnormal findings on the physical exam, ECG, blood/urine or minor infections\n* Any pre-existing physical pain condition, including fibromyalgia\n* History of peptic ulcer complicated by perforation, hemorrhage, or obstruction; symptoms of peptic ulcer within 4 weeks of enrollment date\n* Any substance abuse or dependence during the preceding 12 months\n* Clinically significant hypertension, anemia, liver disease, kidney disease, arthritis, diabetes, recurrent migraines, epilepsy, stroke, gum disease, autoimmune disease\n* Current use of lithium\n* Current use of a stimulant\n* Certain steroids including use of hormonal birth control and any systemic or topical corticosteroids (hormone replacement therapy will be allowed)\n* Unwillingness to refrain from H2 receptor antagonists, non-aspirin NSAIDs, or aspirin (more than 1 mg/day).\n* Use of any anticoagulant agents\n* Use of nicotine-containing substances. Subjects who quit smoking more than 3 months prior to assessment may be considered for the study\n* Known sensitivity or allergy to the study medications or a need to receive agents that are contra-indicated in combination with CBX or ESC\n* Unwillingness to fast and abstain from caffeine on mornings of blood drawings\n* A sleep disorder other than insomnia or hypersomnia as a distinct symptom of major depressive disorder (MDD)\n* Inability to commit to the follow-up visits between 8 and 11 am","healthyVolunteers":false,"sex":"ALL","minimumAge":"21 Years","maximumAge":"65 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Angelo Halaris, MD, PhD","affiliation":"Loyola Univeristy Medical Center","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Loyola University Medical Center","city":"Maywood","state":"Illinois","zip":"60153","country":"United States","geoPoint":{"lat":41.8792,"lon":-87.84312}}]},"referencesModule":{"references":[{"pmid":"31923551","type":"DERIVED","citation":"Murata S, Murphy M, Hoppensteadt D, Fareed J, Welborn A, Halaris A. Effects of adjunctive inflammatory modulation on IL-1beta in treatment resistant bipolar depression. Brain Behav Immun. 2020 Jul;87:369-376. doi: 10.1016/j.bbi.2020.01.004. Epub 2020 Jan 7."},{"pmid":"31630035","type":"DERIVED","citation":"Halaris A, Cantos A, Johnson K, Hakimi M, Sinacore J. Modulation of the inflammatory response benefits treatment-resistant bipolar depression: A randomized clinical trial. J Affect Disord. 2020 Jan 15;261:145-152. doi: 10.1016/j.jad.2019.10.021. Epub 2019 Oct 13."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"One-hundred subjects consented to participate in this study. Among these individuals, 27 participants were screen failures and eight participants withdrew prior to randomization. The remaining 65 participants were randomized and took at least one study capsule","recruitmentDetails":"Participants were recruited from an outpatient psychiatric clinic","groups":[{"id":"FG000","title":"Intervention Cohort","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily."},{"id":"FG001","title":"Control Cohort","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"35"},{"groupId":"FG001","numSubjects":"30"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"27"},{"groupId":"FG001","numSubjects":"20"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"8"},{"groupId":"FG001","numSubjects":"10"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"8"},{"groupId":"FG001","numSubjects":"10"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"The baseline analysis population comprises all patients who were randomized and completed at least eight consecutive weeks of assigned treatment","groups":[{"id":"BG000","title":"Intervention Cohort","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily."},{"id":"BG001","title":"Control Cohort","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"20"},{"groupId":"BG002","value":"47"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"39.48","spread":"10.73"},{"groupId":"BG001","value":"46.15","spread":"13.50"},{"groupId":"BG002","value":"42.32","spread":"12.31"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"15"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"28"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"12"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"19"}]}]}]},{"title":"Race/Ethnicity, Customized","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"Self-described race","categories":[{"title":"White","measurements":[{"groupId":"BG000","value":"19"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"32"}]},{"title":"non-White","measurements":[{"groupId":"BG000","value":"8"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"15"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"20"},{"groupId":"BG002","value":"47"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Response to Treatment","description":"Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, response to treatment is defined as a reduction in the HDRS-17 score of at least 50% after 8 weeks of treatment.","populationDescription":"The analysis population is defined as all participants who completed at least eight weeks of treatment","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Intervention Cohort","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily."},{"id":"OG001","title":"Control Cohort","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"20"}]}],"classes":[{"categories":[{"title":"Response","measurements":[{"groupId":"OG000","value":"21"},{"groupId":"OG001","value":"9"}]},{"title":"No Response","measurements":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"11"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"The null hypothesis is that there is no difference in the response rate between patients assigned to the intervention cohort or control cohort.","nonInferiorityType":"SUPERIORITY","pValue":".02","statisticalMethod":"Chi-squared","paramType":"Chi-square value","paramValue":"5.3466","ciNumSides":"TWO_SIDED","estimateComment":"The chi-square value with 1 degree of freedom was 5.3466."}]},{"type":"PRIMARY","title":"Disease Remission","description":"Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, diisease remission is defined as an HDRS-17 score less than 8 points after 8 weeks of treatment.","populationDescription":"The analysis population is defined as all participants who completed at least eight weeks of treatment","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Intervention Cohort","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily."},{"id":"OG001","title":"Control Cohort","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"20"}]}],"classes":[{"categories":[{"title":"Remission","measurements":[{"groupId":"OG000","value":"17"},{"groupId":"OG001","value":"2"}]},{"title":"No Remission","measurements":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"18"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"The null hypothesis is that there is no difference in the remission rate between patients assigned to the intervention cohort or control cohort.","nonInferiorityType":"SUPERIORITY","pValue":"<.001","statisticalMethod":"Chi-squared","paramType":"Chi-square value","paramValue":"13.3821","ciNumSides":"TWO_SIDED","estimateComment":"The chi-square value with 1 degree of freedom was 13.3821."}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"8 weeks","eventGroups":[{"id":"EG000","title":"Intervention Cohort","description":"Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily.","deathsNumAffected":0,"deathsNumAtRisk":35,"seriousNumAffected":0,"seriousNumAtRisk":35,"otherNumAffected":0,"otherNumAtRisk":35},{"id":"EG001","title":"Control Cohort","description":"Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily.","deathsNumAffected":0,"deathsNumAtRisk":30,"seriousNumAffected":0,"seriousNumAtRisk":30,"otherNumAffected":0,"otherNumAtRisk":30}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Dr. Angelos Halaris","organization":"Loyola University Medical Center","email":"ahalaris@luc.edu","phone":"708-216-3272"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2013-01-10","uploadDate":"2021-06-10T14:07","filename":"Prot_SAP_000.pdf","size":292511},{"typeAbbrev":"ICF","hasProtocol":false,"hasSap":false,"hasIcf":true,"label":"Informed Consent Form","date":"2016-11-16","uploadDate":"2021-06-10T14:09","filename":"ICF_001.pdf","size":185885}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D001714","term":"Bipolar Disorder"},{"id":"D007249","term":"Inflammation"}],"ancestors":[{"id":"D000068105","term":"Bipolar and Related Disorders"},{"id":"D019964","term":"Mood Disorders"},{"id":"D001523","term":"Mental Disorders"},{"id":"D010335","term":"Pathologic Processes"},{"id":"D013568","term":"Pathological Conditions, Signs and Symptoms"}]},"interventionBrowseModule":{"meshes":[{"id":"D000089983","term":"Escitalopram"},{"id":"D000068579","term":"Celecoxib"}],"ancestors":[{"id":"D011437","term":"Propylamines"},{"id":"D000588","term":"Amines"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D009570","term":"Nitriles"},{"id":"D001572","term":"Benzofurans"},{"id":"D006574","term":"Heterocyclic Compounds, 2-Ring"},{"id":"D000072471","term":"Heterocyclic Compounds, Fused-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"},{"id":"D000096926","term":"Benzenesulfonamides"},{"id":"D013449","term":"Sulfonamides"},{"id":"D000577","term":"Amides"},{"id":"D001555","term":"Benzene Derivatives"},{"id":"D006841","term":"Hydrocarbons, Aromatic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"},{"id":"D013450","term":"Sulfones"},{"id":"D013457","term":"Sulfur Compounds"},{"id":"D011720","term":"Pyrazoles"},{"id":"D001393","term":"Azoles"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"}]}},"hasResults":true}