RecruitingPhase 1/2

DON in Pediatric Cerebral Malaria

Malawi152 participantsStarted 2022-08-16

Plain-language summary

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: * Determine the pharmacokinetic (PK) profile of a single dose of DON in children with CM * 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) * 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) * 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 * Exploratory: Explore the metabolic mechanisms of action of adjunctive DON in children with CM Healthy adult participants will receive: * anti-emetic ondansetron * one dose of DON Adults with uncomplicated malaria will receive: * anti-emetic ondansetron * one dose of DON * artemisinin-combination therapies per Malawi Ministry of Health guidelines Pediatric participants will receive: * one dose of DON * anti-emetic ondansetron and per Malawi Ministry of Health guidelines: * enteral lumefantrine-artemether therapy, and * artesunate therapy

Who can participate

Age range12 Months

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: For Healthy Adults (Arm 1): * 18 years and older * Informed consent obtained and ICF signed * Temperature ≤ 37.5 °C * BMI 18.5-25 kg/m2 * Creatinine ≤ 110 mmol/L (≤ 1.2 mg/dL; males) or ≤ 90 mmol/L (≤ 1.0 mg/dL; females) * Hemoglobin ≥ 7 g/dL or hematocrit/ packed-cell volume (PCV) ≥ 20% * Thick or thin blood smear negative for asexual forms of P. falciparum * Negative pregnancy test for persons of child-bearing potential For Adults with Uncomplicated Malaria (Arm 2): * 18 years and older * Informed consent obtained and ICF signed * Temperature ≥ 38 °C or history of fever in the past 24 hours * Thick or thin blood smear positive for asexual forms of P. falciparum (parasite count and speciation documented) * Hemoglobin ≥ 7 g/dL or hematocrit/ PCV ≥ 20% * BMI 18.5-25 kg/m2 * Creatinine ≤ 110 mmol/L (≤ 1.2 mg/dL; males) or ≤ 90 mmol/L (≤ 1.0 mg/dL; females) * Glasgow coma score of 15 * Respiratory rate ≤ 20 breaths/ minute * Oxygen saturation ≥ 90% on room air * Negative pregnancy test for person of child-bearing potential For Children with Cerebral Malaria (Arm 3): * Age 12 months-14 years old * Informed consent obtained and ICF signed by parent or guardian * Temperature ≥ 38 °C or history of fever in the last 24 hours * Thick or thin blood smear positive for asexual forms of P. falciparum * Blantyre coma score ≤ 2 * No other explanation for coma by history or physical exam * Hematocrit or PCV ≥ 18% * Negative pregnancy test for persons of child-bearin…

What they're measuring

Incidence of local AEs occurring within 14 days after the administration of DON

Timeframe: 14 days

Incidence of systemic AEs occurring within 14 days after the administration of DON

Timeframe: 14 days

Incidence of systemic SAEs occurring within 14 days after the administration of DON

Timeframe: 14 days

Trial details

NCT IDNCT05478720

SponsorDouglas Postels, MD, MS

Sponsor typeUNKNOWN

Study typeINTERVENTIONAL

Primary completion2025-12

Contact for this trial

Yamikani Chimalizeni, MD

+265 992 23 32 21 ychimalizeni@medcol.mw

View on ClinicalTrials.gov More Malaria, Cerebral trials

Plain-language summary

Who can participate

Age range12 Months

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Incidence of local AEs occurring within 14 days after the administration of DON

Timeframe: 14 days

Incidence of systemic AEs occurring within 14 days after the administration of DON

Timeframe: 14 days

Incidence of systemic SAEs occurring within 14 days after the administration of DON

Timeframe: 14 days