[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Douglas Postels, MD, MS\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":45},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,1,0,[8],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":16,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":29,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100476037","phase-1-don-in-pediatric-cerebral-malaria-100476037",false,"NCT05478720","DON in Pediatric Cerebral Malaria","DON in Pediatric Cerebral Malaria: A Phase I\u002FIIa Dose-Escalation Safety Study","Inclusion Criteria:\n\nFor Healthy Adults (Part 1):\n\n* 18 years and older\n* Informed consent obtained and ICF signed\n* Temperature ≤ 37.5 °C\n* BMI 18.5-25 kg\u002Fm2\n* Creatinine ≤ 110 mmol\u002FL (≤ 1.2 mg\u002FdL; males) or ≤ 90 mmol\u002FL (≤ 1.0 mg\u002FdL; females)\n* Hemoglobin ≥ 7 g\u002FdL or hematocrit\u002F packed-cell volume (PCV) ≥ 20%\n* Thick or thin blood smear negative for asexual forms of P. falciparum\n* Negative pregnancy test for persons of child-bearing potential\n\nFor Adults with Uncomplicated Malaria (Part 1):\n\n* 18 years and older\n* Informed consent obtained and ICF signed\n* Temperature ≥ 38 °C or history of fever in the past 24 hours\n* Thick or thin blood smear positive for asexual forms of P. falciparum (parasite count and speciation documented)\n* Hemoglobin ≥ 7 g\u002FdL or hematocrit\u002F PCV ≥ 20%\n* BMI 18.5-25 kg\u002Fm2\n* Creatinine ≤ 110 mmol\u002FL (≤ 1.2 mg\u002FdL; males) or ≤ 90 mmol\u002FL (≤ 1.0 mg\u002FdL; females)\n* Glasgow coma score of 15\n* Respiratory rate ≤ 20 breaths\u002F minute\n* Oxygen saturation ≥ 90% on room air\n* Negative pregnancy test for person of child-bearing potential\n\nFor Children with Cerebral Malaria (Part 2):\n\n* Age 12 months-14 years old\n* Informed consent obtained and ICF signed by parent or guardian\n* Temperature ≥ 38 °C or history of fever in the last 24 hours\n* Thick or thin blood smear positive for asexual forms of P. falciparum\n* Blantyre coma score ≤ 2\n* No other explanation for coma by history or physical exam\n* Hematocrit or PCV ≥ 18%\n* Negative pregnancy test for persons of child-bearing potential\n* Creatinine ≤ 1.5 mg\u002FdL\n* Aspartate aminotransferase (AST) \\\u003C 280 IU\u002FL\n* Alanine aminotransferase (ALT) \\\u003C 195 IU\u002FL\n\nExclusion Criteria (All Participants):\n\n* Pregnancy or lactation (participants of child-bearing potential ages 9-59 years will undergo pregnancy testing prior to administration of the intervention)\n* Participants attempting to become pregnant\n* Currently taking highly active antiretroviral therapy (HAART)\n* Currently taking anti-tuberculosis medications\n* Allergy to ondansetron or ceftriaxone\n\nAdditional Exclusion Criteria for Children with Cerebral Malaria (Part 2):\n\n* Cloudy cerebrospinal fluid (indicative of a probable bacterial central nervous system infection)\n* Severe malnutrition (\\>3 standard deviations below the mean weight for height and\u002F or mid-upper arm circumference (MUAC) ≤11.5 cm\n* Allergy to ondansetron or ceftriaxone\n* Coma for \\> 72 hours\n* Have taken a CYP3A4 inhibitor within 7 days of enrollment",true,"ALL","12 Months",{"count":20,"type":21},152,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","The goal of this clinical trial is to evaluate the safety of a single intravenous dose of DON in healthy adults, adults with uncomplicated malaria, and children 12 months-14 years old with clinically defined Cerebral Malaria. The main objectives are:\n\n* Evaluate the safety of a single intravenous dose of DON in healthy adults and adults with uncomplicated malaria ( Part 1)\n* Determine the safety of a single dose of DON in children 12 months-14 years old with World Health Organization (WHO) clinically defined CM (Part 2 :Cohort 1-4)\n* Determine the pharmacokinetic (PK) profile of a single dose of DON in healthy adults, adults with uncomplicated malaria and children with CM (Part 1, and Cohorts 1-4 of Part 2)\n* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with CM is associated with improved intracerebral blood flow dynamics on transcranial doppler (TCD) (Part 2 :Cohort 1-4)\n* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with CM is associated with a reduction in brain volume score on magnetic resonance imaging (MRI) (Part 2 :Cohort 1-4)\n* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with cerebral malaria is associated with changes in electroencephalogram (EEG) pattern (Part 2 :Cohort 1-4)\n* Exploratory: Explore the metabolic mechanisms of action of adjunctive DON in children with CM\n\nHealthy adult participants will receive:\n\n* anti-emetic ondansetron\n* one dose of DON\n\nAdults with uncomplicated malaria will receive:\n\n* anti-emetic ondansetron\n* one dose of DON\n* artemisinin-combination therapies per Malawi Ministry of Health guidelines\n\nPediatric participants will receive:\n\n* one dose of DON\n* anti-emetic ondansetron and per Malawi Ministry of Health guidelines:\n* enteral lumefantrine-artemether therapy, and\n* artesunate therapy",[28],"Malaria, Cerebral",[30,31],"malaria","Plasmodium falciparum","RECRUITING","2026-06-25",{"date":35,"type":36},"2026-06-29","ACTUAL",{"date":38,"type":36},"2022-08-16",{"date":40,"type":21},"2026-12",{"name":42,"class":43},"Douglas Postels, MD, MS","UNKNOWN",2,""]