Evaluating DON for treating pediatric cerebral malaria

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial aims to assess the safety and pharmacokinetics of a single intravenous dose of 6-diazo-5-oxo-L-norleucine (DON) in children aged 12 months to 14 years diagnosed with cerebral malaria. The study will involve a dose escalation approach, where participants will receive varying doses of DON to determine its safety and potential benefits, including improved blood flow dynamics and reduced brain volume. Additionally, the trial will explore metabolic mechanisms of action and monitor changes in EEG patterns. The study will be conducted over three malaria seasons, with a planned interim analysis after the third cohort.

Why it matters

Who can join: the full rules

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-bearing potential
* Creatinine ≤ 1.5 mg/dL
* Aspartate aminotransferase (AST) \< 280 IU/L
* Alanine aminotransferase (ALT) \< 195 IU/L

Exclusion Criteria (All Participants):

* Pregnancy or lactation (participants of child-bearing potential ages 9-59 years will undergo pregnancy testing prior to administration of the intervention)
* Participants attempting to become pregnant
* Currently taking highly active antiretroviral therapy (HAART)
* Currently taking anti-tuberculosis medications
* Allergy to ondansetron or ceftriaxone

Additional Exclusion Criteria for Children with Cerebral Malaria (Part 2):

* Cloudy cerebrospinal fluid (indicative of a probable bacterial central nervous system infection)
* Severe malnutrition (\>3 standard deviations below the mean weight for height and/ or mid-upper arm circumference (MUAC) ≤11.5 cm
* Allergy to ondansetron or ceftriaxone
* Coma for \> 72 hours
* Have taken a CYP3A4 inhibitor within 7 days of enrollment

Where it's running

• Queen Elizabeth Central Hospital
  Blantyre, Malawi Recruiting
• Ndirande Research Clinic
  Blantyre, Malawi Completed

Study contacts

• Principal investigator: Douglas Postels, MD — Children's National Research Institute
• Study coordinator: Yamikani Chimalizeni, MD
• Email: ychimalizeni@medcol.mw
• Phone: +265 992 23 32 21

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.