{"protocolSection":{"identificationModule":{"nctId":"NCT04876521","orgStudyIdInfo":{"id":"AIIMS BBSR/PGThesis/2019-21"},"organization":{"fullName":"All India Institute of Medical Sciences, Bhubaneswar","class":"OTHER"},"briefTitle":"Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression","officialTitle":"Comparative Efficacy and Safety of Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in the Treatment of Post Schizophrenic Depression: A Randomized Controlled Trial","acronym":"PSD-AOFC"},"statusModule":{"statusVerifiedDate":"2024-09","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2019-10-14","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2021-06-09","type":"ACTUAL"},"completionDateStruct":{"date":"2021-06-30","type":"ACTUAL"},"studyFirstSubmitDate":"2021-05-03","studyFirstSubmitQcDate":"2021-05-03","studyFirstPostDateStruct":{"date":"2021-05-06","type":"ACTUAL"},"resultsFirstSubmitDate":"2023-06-03","resultsFirstSubmitQcDate":"2024-09-09","resultsFirstPostDateStruct":{"date":"2024-09-19","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-09-09","lastUpdatePostDateStruct":{"date":"2024-09-19","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"BISWA RANJAN MISHRA","investigatorTitle":"Additional Professor, Department of Psychiatry","investigatorAffiliation":"All India Institute of Medical Sciences, Bhubaneswar"},"leadSponsor":{"name":"All India Institute of Medical Sciences, Bhubaneswar","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false,"isFdaRegulatedDrug":false,"isFdaRegulatedDevice":false},"descriptionModule":{"briefSummary":"Post-Schizophrenic Depression (PSD) increases the morbidity and mortality of Schizophrenic patients. Hence, it warrants early assessment and intervention. But, clinical trials on PSD are very few. However, an Antipsychotic with an adjunctive Antidepressant (like Olanzapine-Fluoxetine Combination) is the commonly prescribed treatment in PSD. Low dose Amisulpride (\\<400 mg/day) which is effective against the negative symptoms of Schizophrenia has also proved efficacious in treating depression in non-psychotic conditions, but its antidepressant property has never been studied in PSD. This is an 8-week, randomized, parallel-group study that will explore the efficacy and safety of low-dose Amisulpride versus Olanzapine-Fluoxetine Combination in the treatment of PSD. Our hypothesis is that low dose Amisulpride has better efficacy and safety versus Olanzapine-Fluoxetine Combination in PSD, after 8-weeks.","detailedDescription":"The proposed study would be an 8-week, randomized, controlled, parallel-group, clinical trial which will be conducted at the Inpatient and Outpatient settings of the Department of Psychiatry, AIIMS, Bhubaneswar. Patients with the diagnosis of Post Schizophrenic Depression according to the ICD 10 (DCR) and meeting all the Inclusion and Exclusion Criteria would be selected for the study. At first, the patients and their family members/ guardians would be explained about the study procedure along with its possible risks and benefits using a Patient Information Sheet (in their local language). After obtaining a written Informed Consent from the Legally Authorised Relative, the patients would be finally recruited for the study.\n\nAll recruited patients would be randomized using computer-generated random numbers into two treatment groups with an allocation ratio of 1:1. The sociodemographic and clinical data of the patients would be collected as per the designed sheets. Then at baseline, the CDSS and CGI ratings would be assessed, and the serum BDNF would be tested for each patient. The study would be rater-blinded. The experimental group would receive Amisulpride at a low dosage of 100-300 mg/day and the control group would receive a combination of Olanzapine at 5mg or 10 mg/day and Fluoxetine at 20mg/day.\n\nThe two groups would be followed for 8 weeks, at the completion of which all the patients would be reassessed. The follow-up assessment would involve a re-evaluation of the CDSS and the CGI scores and the Serum BDNF levels to see for any change. The data thus collected would be analyzed, compared within and in between the study groups and statistical tests would be applied for drawing conclusions. The missing values will be analyzed by an intention-to-treat protocol."},"conditionsModule":{"conditions":["Post-Schizophrenic Depression"],"keywords":["Post-Schizophrenic Depression","Amisulpride","Olanzapine-Fluoxetine Combination","Post Psychotic Depression"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","interventionModelDescription":"Randomized, parallel-group, rater-blinded, clinical trial.","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"SINGLE","maskingDescription":"The proposed study will be rater-blinded. The ratings would be done by a psychiatrist who would be blinded to the nature of the intervention provided","whoMasked":["OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":60,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Amisulpride Group","type":"EXPERIMENTAL","description":"The patients will receive low dose Amisulpride at 100-300 mg/day.","interventionNames":["Drug: Amisulpride"]},{"label":"Olanzapine-Fluoxetine Group","type":"ACTIVE_COMPARATOR","description":"the patients will receive Olanzapine-Fluoxetine Combinations at 5/10 + 20 mg/day.","interventionNames":["Drug: Olanzapine-Fluoxetine Combination"]}],"interventions":[{"type":"DRUG","name":"Amisulpride","description":"low dose of Amisulpride at 100-300 mg/day","armGroupLabels":["Amisulpride Group"],"otherNames":["Sulpitac","Amazeo","Soltus"]},{"type":"DRUG","name":"Olanzapine-Fluoxetine Combination","description":"Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)","armGroupLabels":["Olanzapine-Fluoxetine Group"],"otherNames":["Oleanz Fort","Oleanz Plus"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Calgary Depression Scale for Schizophrenia (CDSS)","description":"Calgary Depression Scale for Schizophrenia (CDSS) scores is used to measure the severity of depressive symptoms in the study groups. The total score ranges from 0 - 36. Higher scores represent a higher severity of depression.","timeFrame":"8 weeks"}],"secondaryOutcomes":[{"measure":"Clinical Global Impression - Severity (CGI) Scale","description":"The Clinical Global Impression - Severity (CGI-S) is a 7-point scale used to measure the severity of the illness in the study groups \\[minimum: 1 and maximum 7\\]: Higher scores mean higher severity of disease.","timeFrame":"8 weeks"},{"measure":"Serum BDNF Levels","description":"The change in serum BDNF levels in the study groups at 8 weeks (in pg/mL)","timeFrame":"8 weeks"},{"measure":"Correlation","description":"Determine the correlation (if any) between the changes in CDSS scores and serum BDNF levels. The correlation coefficient is represented as r, with values from -1 to +1 \\[where +/- 1 mean strongest correlation and 0 mean no correlation\\].","timeFrame":"8 week"},{"measure":"Adverse Drug Reactions","description":"Detect adverse drug reactions (if any) and grading their severity","timeFrame":"8 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Patients with Post Schizophrenic Depression according to ICD10-DCR (International Classification of Diseases 10- Diagnostic Criteria for Research).\n2. Aged between 18 to 60 years of either sex\n3. Patients with a positive score of less than 29 on the Positive and Negative Syndrome Scale (PANSS) \\[88\\]\n4. Patients with a score of more than 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) \\[89-90\\]\n5. Patients without Extrapyramidal symptoms: a score of less than 3 on the Simpson-Angus Scale \\[91\\]\n6. With Informed consent from the Legally Authorised Relative\n\nExclusion Criteria:\n\n1. Patients with a medical or neurological disorder\n2. Patients with a history of substance dependence\n3. Patients with high suicidality\n4. Patients with a past history of primary depression\n5. Patients already on Olanzapine-Fluoxetine combination or Amisulpride","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"60 Years","stdAges":["ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Biswa R Mishra, MD","affiliation":"All India Institute of Medical Sciences, Bhubaneswar","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"All India Institute of Medical Sciences","city":"Bhubaneswar","state":"Odisha","zip":"DR BISWA RANJAN MISHRA","country":"India","geoPoint":{"lat":20.27241,"lon":85.83385}}]},"referencesModule":{"references":[{"pmid":"3630758","type":"BACKGROUND","citation":"Berrios GE, Bulbena A. Post psychotic depression: the Fulbourn cohort. Acta Psychiatr Scand. 1987 Jul;76(1):89-93. doi: 10.1111/j.1600-0447.1987.tb02866.x."},{"pmid":"4637572","type":"BACKGROUND","citation":"Stern MJ, Pillsbury JA, Sonnenberg SM. Postpsychotic depression in schizophrenics. Compr Psychiatry. 1972 Nov-Dec;13(6):591-8. doi: 10.1016/0010-440x(72)90060-0. No abstract available."},{"pmid":"28503978","type":"BACKGROUND","citation":"Rahim T, Rashid R. Comparison of depression symptoms between primary depression and secondary-to-schizophrenia depression. Int J Psychiatry Clin Pract. 2017 Nov;21(4):314-317. doi: 10.1080/13651501.2017.1324036. Epub 2017 May 15."},{"pmid":"12785461","type":"BACKGROUND","citation":"Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med. 2003 May;33(4):589-99. doi: 10.1017/s0033291703007645."},{"pmid":"2278986","type":"BACKGROUND","citation":"Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res. 1990 Jul-Aug;3(4):247-51. doi: 10.1016/0920-9964(90)90005-r."},{"pmid":"14642970","type":"BACKGROUND","citation":"Moller HJ. Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1101-11. doi: 10.1016/j.pnpbp.2003.09.006."},{"pmid":"20334574","type":"BACKGROUND","citation":"Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry. 2010 Sep;11(6):763-73. doi: 10.3109/15622971003611319."},{"pmid":"38560960","type":"DERIVED","citation":"Biswas T, Mishra BR, Maiti R, Padhy SK, Mishra A. Efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination in post-schizophrenic depression: A randomized controlled trial. J Psychiatr Res. 2024 May;173:302-308. doi: 10.1016/j.jpsychires.2024.03.048. Epub 2024 Mar 28."}]},"ipdSharingStatementModule":{"ipdSharing":"NO","description":"To maintain the confidentiality of the participants."}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Amisulpride Group","description":"The patients received Amisulpride at 100-300 mg/day.\n\nAmisulpride: Amisulpride at 100-300 mg/day"},{"id":"FG001","title":"Olanzapine-Fluoxetine Group","description":"the patients received Olanzapine-Fluoxetine Combinations at 5/10-5/20 mg/day.\n\nOlanzapine-Fluoxetine Combination: Olanzapine (5 mg/day) and Fluoxetine (10-20 mg/day)"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"30"},{"groupId":"FG001","numSubjects":"30"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"25"},{"groupId":"FG001","numSubjects":"23"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"5"},{"groupId":"FG001","numSubjects":"7"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"BG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"30"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"60"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"30"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"60"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"35.2","spread":"10.1"},{"groupId":"BG001","value":"35.4","spread":"9.8"},{"groupId":"BG002","value":"35.3","spread":"9.9"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"30"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"60"}]}],"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"12"},{"groupId":"BG002","value":"25"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"17"},{"groupId":"BG001","value":"18"},{"groupId":"BG002","value":"35"}]}]}]},{"title":"Race and Ethnicity Not Collected","populationDescription":"Race and Ethnicity were not collected from any participant.","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}],"categories":[{"measurements":[{"groupId":"BG002","value":"0"}]}]}]},{"title":"PANSS-P score","description":"The Positive and Negative Syndrome Scale - Positive (PANSS-P) is a medical scale that measures the severity of positive symptoms of schizophrenia. It has seven items (delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution and hostility). Each item has a score range of 1 to 7. Thus, the total minimum score is 7, and the total maximum score is 49. Higher scores mean more severity of symptoms.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"score on a scale","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"30"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"60"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"13.70","spread":"4.44"},{"groupId":"BG001","value":"13.80","spread":"4.22"},{"groupId":"BG002","value":"13.75","spread":"4.29"}]}]}]},{"title":"MADRS score","description":"The Montgomery-Asberg Depression Rating Scale (MADRS) is a ten-item scale used to measure the severity of depressive symptoms in a patient. Each item has a score ranging from 0 to 6. Thus, the total minimum score is 0, and the total maximum score is 60. The higher the score, the more severe the depressive symptoms.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"score on a scale","classes":[{"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"30"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"60"}]}],"categories":[{"measurements":[{"groupId":"BG000","value":"23.17","spread":"6.49"},{"groupId":"BG001","value":"23.73","spread":"6.82"},{"groupId":"BG002","value":"23.45","spread":"6.61"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Calgary Depression Scale for Schizophrenia (CDSS)","description":"Calgary Depression Scale for Schizophrenia (CDSS) scores is used to measure the severity of depressive symptoms in the study groups. The total score ranges from 0 - 36. Higher scores represent a higher severity of depression.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"score on a scale","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"OG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"23"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"8.31","spread":"0.47"},{"groupId":"OG001","value":"8.62","spread":"0.60"}]}]}]},{"type":"SECONDARY","title":"Clinical Global Impression - Severity (CGI) Scale","description":"The Clinical Global Impression - Severity (CGI-S) is a 7-point scale used to measure the severity of the illness in the study groups \\[minimum: 1 and maximum 7\\]: Higher scores mean higher severity of disease.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"units on a scale","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"OG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"23"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"3.31","spread":"0.09"},{"groupId":"OG001","value":"3.44","spread":"0.11"}]}]}]},{"type":"SECONDARY","title":"Serum BDNF Levels","description":"The change in serum BDNF levels in the study groups at 8 weeks (in pg/mL)","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"picograms per milliliter","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"OG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"23"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1453.59","spread":"44.62"},{"groupId":"OG001","value":"1471.19","spread":"48.22"}]}]}]},{"type":"SECONDARY","title":"Correlation","description":"Determine the correlation (if any) between the changes in CDSS scores and serum BDNF levels. The correlation coefficient is represented as r, with values from -1 to +1 \\[where +/- 1 mean strongest correlation and 0 mean no correlation\\].","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"r (correlation coefficient)","timeFrame":"8 week","groups":[{"id":"OG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"OG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"23"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.161"},{"groupId":"OG001","value":"-0.123"}]}]}]},{"type":"SECONDARY","title":"Adverse Drug Reactions","description":"Detect adverse drug reactions (if any) and grading their severity","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"8 weeks","groups":[{"id":"OG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day"},{"id":"OG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"25"},{"groupId":"OG001","value":"23"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"8 weeks","eventGroups":[{"id":"EG000","title":"Amisulpride Group","description":"Received Amisulpride at 100-300 mg/day","deathsNumAffected":0,"deathsNumAtRisk":30,"seriousNumAffected":0,"seriousNumAtRisk":30,"otherNumAffected":0,"otherNumAtRisk":30},{"id":"EG001","title":"Olanzapine-Fluoxetine Group","description":"Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)","deathsNumAffected":0,"deathsNumAtRisk":30,"seriousNumAffected":0,"seriousNumAtRisk":30,"otherNumAffected":0,"otherNumAtRisk":30}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"1. Small sample size\n2. Single-center study\n3. No control arm for comparing the Serum BDNF levels"},"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Dr. Biswa Ranjan Mishra","organization":"All India Institute of Medical Sciences","email":"psych_biswa@aiimsbhubaneswar.edu.in","phone":"09438884220"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP_ICF","hasProtocol":true,"hasSap":true,"hasIcf":true,"label":"Study Protocol, Statistical Analysis Plan, and Informed Consent Form","date":"2019-06-01","uploadDate":"2024-04-03T14:50","filename":"Prot_SAP_ICF_000.pdf","size":310088}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"interventionBrowseModule":{"meshes":[{"id":"D000077582","term":"Amisulpride"},{"id":"C492572","term":"olanzapine-fluoxetine combination"}],"ancestors":[{"id":"D001549","term":"Benzamides"},{"id":"D000577","term":"Amides"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D001565","term":"Benzoates"},{"id":"D000146","term":"Acids, Carbocyclic"},{"id":"D002264","term":"Carboxylic Acids"},{"id":"D001555","term":"Benzene Derivatives"},{"id":"D006841","term":"Hydrocarbons, Aromatic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"}]}},"hasResults":true}