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New treatment option for Malaria, Cerebral
Official title DON in Pediatric Cerebral Malaria
ClinicalTrials.gov ID: NCT05478720
What this study is testing
What is 6-diazo-5-oxo-L-norleucine (DON)?
6-diazo-5-oxo-L-norleucine (DON) is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for malaria, cerebral.
Also referred to as NSC 7365.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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
- Phase 2: a mid-size study of how well it works
- You might receive a placebo (an inactive treatment) instead of the study drug, decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 12 and older. Healthy volunteers may be eligible.
You may be able to join if
- 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
You likely can't join if
- (All Participants):
- Pregnancy or lactation (participants of child-bearing potential ages 9-59 years will undergo pregnancy testing prior to administration of the...
- 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):
See the full eligibility 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
- (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
The study team makes the final eligibility decision.
Where it's taking place
- Blantyre, Malawi
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 12 months and older. Healthy volunteers may be eligible. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Blantyre, Malawi. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.