Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2025-12-26 @ 12:24 AM
Study NCT ID:
NCT05632094
Status:
UNKNOWN
Last Update Posted:
2022-12-02
First Post:
2022-11-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The Efficacy of L-Carnitine in the Management of Acute Clozapine Intoxication
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D002331', 'term': 'Carnitine'}], 'ancestors': [{'id': 'D050337', 'term': 'Trimethyl Ammonium Compounds'}, {'id': 'D000644', 'term': 'Quaternary Ammonium Compounds'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Clinical controlled randomized clinical trial (phase II) will be conducted in Poison Center. The total required sample size is 40 patients who suffer from acute clozapine intoxication.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2023-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'completionDateStruct': {'date': '2024-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-11-30', 'studyFirstSubmitDate': '2022-11-10', 'studyFirstSubmitQcDate': '2022-11-19', 'lastUpdatePostDateStruct': {'date': '2022-12-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-11-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Mortality', 'timeFrame': 'up to 14 days', 'description': 'Death'}, {'measure': 'Neurotoxicity', 'timeFrame': 'up to 14 days', 'description': 'Changes in Scores of Glasgow Coma Scale (GCS). GCS is scored between 3 and 15, with 3 being the worst and 15 the best.'}, {'measure': 'Cardiotoxicity', 'timeFrame': 'up to 14 days', 'description': 'Changes in the rate of sinus rhythm and QT interval in Electrocardiogram'}], 'secondaryOutcomes': [{'measure': 'Intensive care unit admission', 'timeFrame': 'up to 14 days', 'description': 'Number of patients who need intensive care unit admission'}, {'measure': 'Duration of hospital stay', 'timeFrame': 'up to 14 days', 'description': 'Hours passed since admission till discharge or death'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Clozapine Toxicity', 'Clozapine Poisoning', 'Clozapine Intoxication', 'L-Carnitine', 'Antioxidant', 'Egypt'], 'conditions': ['Clozapine Poisoning']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': 'Abbas MF, Abbas AH. Clozapine-induced myocarditis in rats: role of L-carnitine in protection. The Egypt J. Forensic Sci. Appli. Toxicol. 2016; 16(1): 141-157. doi: 10.21608/ejfsat.2016.39958'}, {'pmid': '30465787', 'type': 'BACKGROUND', 'citation': 'Wang W, Bai M, Jiang T, Li C, Li P, Zhou H, Wang Z, Li L, Jiang H. Clozapine-induced reduction of l-carnitine reabsorption via inhibition/down-regulation of renal carnitine/organic cation transporter 2 contributes to liver lipid metabolic disorder in mice. Toxicol Appl Pharmacol. 2019 Jan 15;363:47-56. doi: 10.1016/j.taap.2018.11.007. Epub 2018 Nov 19.'}, {'type': 'BACKGROUND', 'citation': 'Pourahmad J, Salimi A, Imani F, Jamali Z, Ahvar N. The clozapine-induced toxicity via induction of oxidative stress and mitochondrial dysfunction in human blood lymphocytes and protecting role of L-Carnitine. Int. pharm. acta. 2020;3(1), 3e9:1-9. https://doi.org/10.22037/ipa.v3i1.32179'}, {'pmid': '32440337', 'type': 'BACKGROUND', 'citation': 'Sherif NA, El-Banna AS, ElBourini MM, Khalil NO. Efficacy of L-carnitine and propranolol in the management of acute theophylline toxicity. Toxicol Res (Camb). 2020 Mar 11;9(1):45-54. doi: 10.1093/toxres/tfaa002. eCollection 2020 Feb.'}, {'pmid': '33401984', 'type': 'BACKGROUND', 'citation': 'Elgazzar FM, Elgohary MS, Basiouny SM, Lashin HI. Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning. Hum Exp Toxicol. 2021 Jul;40(7):1053-1063. doi: 10.1177/0960327120983873. Epub 2021 Jan 5.'}]}, 'descriptionModule': {'briefSummary': "Clozapine is a dibenzodiazepine that is used atypical antipsychotic drug. Clozapine-induced cytotoxicity could be attributed to increases in reactive oxygen species (ROS) that oxidize mitochondrial proteins and disrupt cellular respiration.\n\nL-Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) is an endogenous mitochondrial membrane compound that is essential for the normal functions of mitochondria. L-Carnitine is an effective ROS scavenger that prevents lipid peroxidation.\n\nIn an animal study, it was observed that clozapine decrease L-Carnitine level in plasma which results in metabolic disorders. Subsequently, the use of supplementation L-Carnitine was recommended to attenuate clozapine-induced side effects.\n\nAn in-vitro study investigated the cytotoxic effects of clozapine on human lymphocytes and the possible protective role of L-Carnitine, the results revealed that clozapine-induced cytotoxicity attributed to oxidative stress and mitochondrial dysfunction which significantly improved upon L-Carnitine administration.\n\nIn clinical toxicology, acute clozapine toxicity results in significant morbidities and mortalities in absence of a specific antidote. Therefore, it is essential to adopt pharmaceutical intervention based on the proposed mechanism of clozapine-induced cytotoxicity.\n\nThe objective of the current research is to assess the potential beneficial effects of L-Carnitine on the acute clozapine poisoning outcome.\n\nThe study will include patients with moderate and severe acute clozapine poisoning. The patient's condition will be assessed on admission using a Poisoning Severity Score.\n\nPatients with acute clozapine poisoning will be assigned randomly into two groups; the Conventional group and the L-Carnitine group. Then, all patients will be closely followed up for vital signs, Glasgow Coma Scale, and Electrocardiogram. Clinical and laboratory reassessments will be performed. Lastly, the outcomes will be assessed and statistical analysis of the results will be performed.\n\nEthical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Alexandria University. This Ethics Committee is constituted and operates according to ICH GCP Guidelines and applicable local and institutional regulations and guidelines that govern the Ethics Committees operation. Written informed consent will be obtained from clozapine-intoxicated patients or their guardians (minors or those with disturbed mental status). Full details regarding the study's aim and procedures will be provided to all participants. A code number will be assigned to ensure confidentiality and anonymous analysis of data.", 'detailedDescription': 'Study design:\n\nClinical controlled randomized clinical trial (phase II) will be conducted in Poison Center. The total required sample size is 40 patients, similar to the sample size calculated in the clinical trial that verified the efficacy of IV lipid emulsion in managing clozapine toxicity.\n\nThe diagnosis will be based on the history of intake of a large dose of clozapine along with the presence of the pill container. The diagnosis of acute clozapine toxicity will be supported by the clinical findings that include significant central nervous system depression, hypotension, tachycardia, and prolongation of QT interval.\n\nAll patients will be subject to the following:\n\n* History taking: Sociodemographic data, the amount of ingested drug, time past since ingestion, pre-hospital management, current medical complaints, past medical and surgical history.\n* Clinical assessment: Glasgow coma scale, vital signs, and general examination).\n* Laboratory investigations that included: arterial blood gases (ABG), complete blood count, serum sodium and potassium levels, blood glucose level, liver functions (bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT)), renal functions (urea, creatinine, blood urea nitrogen (BUN)) and cardiac enzymes.\n* Electrocardiogram.\n* Calculation of Poisoning Severity Score (PSS) that classifies poisoning severity as none (0), minor (1), moderate (2), severe (3), and fatal (4).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* The study will include patients with moderate and severe acute clozapine poisoning. The patient's condition will be assessed on admission using a Poisoning Severity Score.\n\nExclusion criteria:\n\n* When the diagnosis of acute clozapine poisoning is unconfirmed.\n* Patients with significant comorbidities, especially advanced neurological and cardiac diseases.\n* Patients that ingest other drugs other than clozapine.\n* Patients who presented late to the poison center (\\>24 hr) following clozapine intake.\n* Patients received treatment before hospital admission."}, 'identificationModule': {'nctId': 'NCT05632094', 'briefTitle': 'The Efficacy of L-Carnitine in the Management of Acute Clozapine Intoxication', 'organization': {'class': 'OTHER', 'fullName': 'Alexandria University'}, 'officialTitle': 'The Efficacy of L-Carnitine in the Management of Acute Clozapine Intoxication', 'orgStudyIdInfo': {'id': '2302'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Conventional Group', 'description': 'This group will comprise 20 patients who will receive conventional supportive care for the treatment of acute clozapine toxicity that include the following:\n\n* Airway: maintaining clear patent airways.\n* Breathing: oxygen inhalation, respiratory support whenever required (mechanical ventilation).\n* Circulation: intravenous fluids, and symptomatic treatment according to ECG abnormalities.\n* Decontamination: administration of activated charcoal (1 gm/kg).'}, {'type': 'EXPERIMENTAL', 'label': 'L-Carnitine Group', 'description': 'This group will comprise 20 patients who will receive conventional supportive care (same as group 1), in addition to IV L-carnitine', 'interventionNames': ['Dietary Supplement: L-Carnitine']}], 'interventions': [{'name': 'L-Carnitine', 'type': 'DIETARY_SUPPLEMENT', 'description': 'The clozapine-intoxicated patients will receive conventional supportive care in addition to IV L-carnitine with a loading dose of 100 mg/kg IV over 30-60 min (maximum 6 g) and the maintenance dose was 50 mg/kg IV every 8 h.', 'armGroupLabels': ['L-Carnitine Group']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Zahraa K Sobh, MD', 'role': 'CONTACT', 'email': 'zahraa.sobh@alexmed.edu.eg', 'phone': '01020744739', 'phoneExt': '+2'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'The confidentiality of the personal data of participants will be maintained. I intended to publish the current study in an international academic journal. Then, the published data could be accessed and used for any purpose.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Alexandria University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Forensic Medicine and Clinical Toxicology', 'investigatorFullName': 'zahraa khalifa sobh', 'investigatorAffiliation': 'Alexandria University'}}}}