DON in Pediatric Cerebral Malaria
Malaria, Cerebral
About this trial
This is an interventional treatment trial for Malaria, Cerebral focused on measuring malaria, Plasmodium falciparum
Eligibility Criteria
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 60-110 mmol/L (0.7-1.2 mg/dL; males) or 45-90 mmol/L (0.5-1.0 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 person 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 60-110 mmol/L (0.7-1.2 mg/dL; males) or 45-90 mmol/L (0.5-1.0 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 6 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 of Glasgow Coma Score ≤ 10.
- No other explanation for coma by history or physical exam
- Greater than 1 hour from last clinical seizure
- Hematocrit or PCV ≥ 18%
- Negative pregnancy test for persons of child-bearing potential
Exclusion Criteria (All Participants):
- Pregnancy or lactation (female participants 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
Additional Exclusion criteria for Children with Cerebral Malaria (Arm 3):
- Positive Kernig or Brudzinski sign
- CSF white blood cell count ≥ 10 /μL
- 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
Sites / Locations
- Ndirande Research ClinicRecruiting
- Queen Elizabeth Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Dose escalation in healthy Malawian adults - 0.1 mg/kg IV DON
Dose escalation in healthy Malawian adults - 1.0 mg/kg IV DON
Dose escalation in healthy Malawian adults - 5.0 mg/kg IV DON
Dose escalation in healthy Malawian adults - 10.0 mg/kg IV DON
Dose escalation in Malawian adults with uncomplicated malaria - 0.1 mg/kg IV DON
Dose escalation in Malawian adults with uncomplicated malaria - 1.0 mg/kg IV DON
Dose escalation in Malawian adults with uncomplicated malaria - 5.0 mg/kg IV DON
Dose escalation in Malawian adults with uncomplicated malaria - 10.0 mg/kg IV DON
Dose escalation in Malawian children with cerebral malaria - 0.1 mg/kg IV DON
Dose escalation in Malawian children with cerebral malaria - 1.0 mg/kg IV DON
Dose escalation in Malawian children with cerebral malaria - 5.0 mg/kg IV DON
Dose escalation in Malawian children with cerebral malaria - 10.0 mg/kg IV DON
Dose escalation in Malawian children with cerebral malaria - placebo
The first 10 healthy adult participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON the final group will receive 10.0 mg/kg IV DON.
The first 10 healthy adult participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON the final group will receive 10.0 mg/kg IV DON.
The first 10 healthy adult participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON the final group will receive 10.0 mg/kg IV DON.
The first 10 healthy adult participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON the final group will receive 10.0 mg/kg IV DON.
The first 10 adults with uncomplicated malaria participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON, and then the final group will receive 10.0 mg/kg IV DON.
The first 10 adults with uncomplicated malaria participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON, and then the final group will receive 10.0 mg/kg IV DON.
The first 10 adults with uncomplicated malaria participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON, and then the final group will receive 10.0 mg/kg IV DON.
The first 10 adults with uncomplicated malaria participants enrolled will receive a single 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, in each subsequent group of 10, the dose will be increased to 1.0 mg/kg IV DON and then 5.0 mg/kg IV DON, and then the final group will receive 10.0 mg/kg IV DON.
During the 2nd year after adult doses are shown to be safe. The first 6 children with cerebral malaria enrolled will receive 0.1 mg/kg IV DON, and 2 will receive placebo. If this dose is proven safe, in the third year, 10 more patients will receive 0.1 mg/kg IV DON, 14 patients will receive 1.0 mg/kg IV DON, and 5 will receive placebo. Should promising risk-benefit ratio profile be shown in year 2 and 3, the study will continue with increased doses of 5.0 mg/kg IV DON, and 10.0 mg/kg IV DON, and 7 placebo patients.
During the 2nd year after adult doses are shown to be safe. The first 6 children with cerebral malaria enrolled will receive 0.1 mg/kg IV DON, and 2 will receive placebo. If this dose is proven safe, in the third year, 10 more patients will receive 0.1 mg/kg IV DON, 14 patients will receive 1.0 mg/kg IV DON, and 5 will receive placebo. Should promising risk-benefit ratio profile be shown in year 2 and 3, the study will continue with increased doses of 5.0 mg/kg IV DON, and 10.0 mg/kg IV DON, and 7 placebo patients.
During the 2nd year after adult doses are shown to be safe. The first 6 children with cerebral malaria enrolled will receive 0.1 mg/kg IV DON, and 2 will receive placebo. If this dose is proven safe, in the third year, 10 more patients will receive 0.1 mg/kg IV DON, 14 patients will receive 1.0 mg/kg IV DON, and 5 will receive placebo. Should promising risk-benefit ratio profile be shown in year 2 and 3, the study will continue with increased doses of 5.0 mg/kg IV DON, and 10.0 mg/kg IV DON, and 7 placebo patients.
During the 2nd year after adult doses are shown to be safe. The first 6 children with cerebral malaria enrolled will receive 0.1 mg/kg IV DON, and 2 will receive placebo. If this dose is proven safe, in the third year, 10 more patients will receive 0.1 mg/kg IV DON, 14 patients will receive 1.0 mg/kg IV DON, and 5 will receive placebo. Should promising risk-benefit ratio profile be shown in year 2 and 3, the study will continue with increased doses of 5.0 mg/kg IV DON, and 10.0 mg/kg IV DON, and 7 placebo patients.
During the 2nd year after adult doses are shown to be safe. The first 6 children with cerebral malaria enrolled will receive 0.1 mg/kg IV DON, and 2 will receive placebo. If this dose is proven safe, in the third year, 10 more patients will receive 0.1 mg/kg IV DON, 14 patients will receive 1.0 mg/kg IV DON, and 5 will receive placebo. Should promising risk-benefit ratio profile be shown in year 2 and 3, the study will continue with increased doses of 5.0 mg/kg IV DON, and 10.0 mg/kg IV DON, and 7 placebo patients.