DON in Pediatric Cerebral Malaria

DON in Pediatric Cerebral Malaria: A Phase I/IIa Dose-Escalation Safety Study

DON in Pediatric Cerebral Malaria (NCT05478720) is a Phase 1 / Phase 2 interventional studying Malaria, Cerebral, sponsored by Douglas Postels, MD, MS. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Malaria, Cerebral, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 152 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Malaria, Cerebral subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: For Healthy Adults (Arm 1): - 18 years and older - willing to sign a consent form 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) - blood count (hemoglobin) at least 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 - willing to sign a consent form 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) - blood count (hemoglobin) at least 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 - willing to sign a consent form 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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-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 Additional Exclusion Criteria for Children with Cerebral Malaria (Arm 3): * Cloudy cerebrospinal fluid (indicative of a probable bacterial central nervous system infection) * Malnutrition defined as a more than or equal to two standard deviations below the mean weight for height and/ or MUAC ≤ 12.5 cm (due to inability to adequately care for children with severe malnutrition on the PRW) * Allergy to ondansetron or ceftriaxone * Coma for \> 72 hours * Have taken a CYP3A4 inhibitor within 7 days of enrollment

Treatments Being Tested

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

Locations (2)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Ndirande Research Clinic

Blantyre, Malawi

Queen Elizabeth Central Hospital

Blantyre, Malawi

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05478720), the sponsor (Douglas Postels, MD, MS), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05478720 clinical trial studying?

Who can participate in NCT05478720?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05478720?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05478720. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05478720. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.