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: * Evaluate the safety of a single intravenous dose of DON in healthy adults and adults with uncomplicated malaria ( Part 1) * 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) * 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) * 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) * 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) * 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) * 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 range

12 Months

Sex

ALL

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 (Part 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 (Part 1): * 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 (Part 2): * 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-bea…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

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

Assessment of Blantyre Coma Score

Timeframe: 14 days

Trial details

NCT IDNCT05478720

SponsorDouglas Postels, MD, MS

Sponsor typeUNKNOWN

Study typeINTERVENTIONAL

Primary completion2026-12

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 range

12 Months

Sex

ALL

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

Assessment of Blantyre Coma Score

Timeframe: 14 days