An interventional study of Rosiglitazone and Placebo in Malaria, sponsored by Centro de Investigacao em Saude de Manhica. Completed at 1 site in Mozambique. Open to participants aged 12 Months to 12 Years. Per ClinicalTrials.gov, last updated 2024-02-21.
Sponsored by Centro de Investigacao em Saude de Manhica · Not applicable, Interventional, and Treatment
Even with optimal anti-malaria therapy and supportive care, severe and cerebral malaria are associated with a 10-30% mortality rate and neurocognitive deficits in up to 33% of survivors. Adjunctive therapies that modify host immune-pathological processes may further improve outcome over that possible with anti-malarials alone. Investigators aim to evaluate a PPARγ agonist ( "rosiglitazone") as adjunctive therapy for severe malaria.
Although the use of artemisinin-based therapy has improved outcomes in severe malaria, the mortality rates remain high. Adjunctive therapies that target the underlying immunopathology may further reduce morbidity and mortality in severe and cerebral malaria beyond that possible with anti-malarials alone. Pre-clinical data have established a beneficial role for PPARγ agonists in experimental cerebral malaria. A proof-of-concept randomized clinical trial of uncomplicated malaria in Thailand has extended these findings to an informative patient population, showing that adjunctive treatment with the PPARγ agonist rosiglitazone improves parasite clearance, and reduces biomarkers of inflammation (IL-6 and MCP-1) and endothelial activation (Ang-2 to Ang-1 ratio), and increases neuro-protective pathways (BDNF). The previous clinical trial also established the safety and tolerability of short course rosiglitazone in adults with malaria infection. Importantly, rosiglitazone does not induce insulin release or hypoglycemia in malaria-infected patients. Based on these data, and on studies demonstrating neuro-protective effects on PPARγ agonists in CNS disease and injury, the investigators believe that PPARγ agonists are promising candidates for adjunctive therapy for severe and cerebral malaria.
In this study the efficacy of rosiglitazone vs. placebo control as adjunct to standard of care anti-malarial therapy in children with severe (including cerebral) malaria will be tested.
The underlying hypothesis is that the addition of rosiglitazone to standard antimalarial therapy in severe P. falciparum infection is safe and will result in improved clinical outcomes and lower rates of long-term neurocognitive impairment.
1,299 studies on the registry are indexed under Malaria; 86 are open to participants now.
This study's enrollment of 210 is close to the median of 220 across 1,027 interventional studies indexed under Malaria.
Browse Malaria studies →Centro de Investigacao em Saude de Manhica is the lead sponsor of 10 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
Participants will receive rosiglitazone 0.045mg/kg/dose twice daily dosing, for 4 days
Drug: Rosiglitazone
Participants will receive placebo (grounded placebo powder) at a dose of 0.045mg/kg/dose twice daily for 4 days
Drug: Placebo
This is the experimental drug, rosiglitazone, being tested against placebo to assess its efficacy as an adjunctive treatment for severe malaria
Also known as: Avandia
This is the placebo control
Also known as: crushed powder placebo
Change in serum Ang-2 levels in the first 96 hours of hospital admission.
We will assess the effect of the intervention (vs. placebo) on Ang-2 levels as a biomarker of severe disease in severe malaria
Time frame: first 96 hours of hospital admission.
Time to clinical recovery
Time to recovery including: 1. Time to fever resolution for at least 24h. Temperature measurements will be taken at admission and every 4h for the first 4 days, and then every 12h until 2 normal results (\<37.5oC) are reported. 2. Time to sit unsupported 3. Time to hospital discharge
Time frame: up to 96 hours after hospital admission
Time to parasitological recovery
Time to parasitological recovery: Time (in hours) to clearance of parasitemia from the blood (both 50% and 90% decrease from admission baseline value). Parasitemia will be quantified at admission and every 6h, for 4 days or until 2 negative readings are reported.
Time frame: up to 96 hours after hospital admission
Mortality
Mortality in the first 48h post-hospital admission and at 14 days post-hospital admission
Time frame: first 48h post-hospital admission and at 14 days post-hospital admission
Blood lactate levels, assessed at admission, every 12h for 24 hours then daily for Blood lactate levels
Blood lactate levels, assessed at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups
Time frame: Assessed at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups
Change in levels of biomarkers of host response
Change in levels of biomarkers of host response at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups
Time frame: at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups
Blood glucose levels
Blood glucose levels assessed at admission and every 6h for the first 48h, and then every 24h for following 2 days
Time frame: up to 96 hours after hospital admission
Cardiac effects
Monitor for cardiac effects by conducting ECG at baseline, at 24h (immediately before third doses of rosiglitazone and artesunate treatment are administered) and at the end of rosiglitazone treatment (day 4). Main outcome of interest will be changes in QTc from baseline to the two different time points.
Time frame: from baseline to 24h, and day 4
Biochemical and hematological parameters
Biochemical and hematological parameters including: AST, ALT, creatinine, complete blood count (e.g. hemoglobin, WBC and differential, hematocrit, platelet count) will be assessed at admission and every 24h until day 4
Time frame: up to 96 hours after hospital admission
AE/SAE
AE/SAE monitored using the pediatric toxicity tables modified from the US National Institutes of Allergy and Infectious Diseases
Time frame: up to day 14 after hospital admission
Neurocognitive outcomes
Participants with Adverse Events that Are Related and unrelated to Treatment by a variety of standard neurocognitive tests
Time frame: From baseline to 6 months post discharge, and 18 months post discharge
Plan to share: No
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Centro de Investigacao em Saude de Manhica