DON in Pediatric Cerebral Malaria

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

Conditions

• Malaria, Cerebral

Interventions

DRUG

6-diazo-5-oxo-L-norleucine (DON)

Single intravenous dose ranging from 0.1-10 mg/kg per dose

DRUG

Placebo

Single intravenous dose of saline

DRUG

6-diazo-5-oxo-L-norleucine (DON)

Single intravenous dose ranging from 0.1-1.0 mg/kg per dose

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• Douglas Postels, MD, MS

  lead UNKNOWN

Principal Investigators

• Douglas Postels, MD · Children's National Research Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

12 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-08-16

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• Malawi

Study Locations