An interventional study of Primaquine in Malaria, Vivax Malaria and Relapse, sponsored by Armed Forces Research Institute of Medical Sciences, Thailand. Status unknown at 1 site in Thailand. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-14.
Sponsored by Armed Forces Research Institute of Medical Sciences, Thailand · Not applicable, Interventional, and Treatment
Plasmodium vivax malaria is difficult to manage because even after taking medicine that kills the infection in the blood, it can continue to hide quietly in the liver, later re-emerging into the blood and causing another episode of malaria illness (relapse). This clinical trial aims to enroll patient with P. vivax infections and try to detect signals in blood, urine and/or saliva coming from the silent liver stages to help identify who could benefit from treatment with primaquine. It also will explore if certain factors of patients negatively impact primaquine efficacy.
Plasmodium vivax, the most widely distributed human malaria, has resisted control largely due to a relapsing hypnozoite liver stage that is clinically silent until emergence and replication in the blood weeks to months later. Curative treatment with primaquine is often not achieved due to potential toxicity in those with G6PD deficiency, poor adherence to the two-week course, and ineffective metabolism of primaquine in those with polymorphisms in cytochrome P450 isoenzyme 2D6 (CYP2D6). Identifying those who harbor hypnozoites will allow for judicious use of primaquine in returning travelers/active duty personnel as well as targeted administration to those living in endemic areas to interrupt parasite transmission in the community. The trial will be conducted in patients presenting with uncomplicated P. vivax malaria at clinical trial sites run by Armed Forces Research Institute of Medical Sciences (AFRIMS) in Southeast Asia. It is designed to capture vivax patients who still harbor the dormant liver stage hypnozoites after treatment with a short acting oral blood schizonticide, and subsequently relapse during the follow-up period while staying in in study-provided housing to reduce risk of reinfection and surveilled daily for parasites or clinical signs of relapse. Longitudinal blood and urine sampling will be done to allow for retrospective analysis to identify biomarkers of hypnozoite infection and subsequent relapse using a systems biology approach. A smaller arm will be enrolled and will receive the short-activing schizonticide with primaquine radical cure at time of admission and followed similarly for relapse. All subjects will be followed for a total of 6 months in order to assess effectiveness of primaquine radical cure for P. vivax infections.
1,299 studies on the registry are indexed under Malaria; 86 are open to participants now.
This study's planned enrollment of 100 is below the median of 220 across 1,027 interventional studies indexed under Malaria.
Browse Malaria studies →Armed Forces Research Institute of Medical Sciences, Thailand is the lead sponsor of 10 studies on the registry; none are open to participants now.
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For P. vivax-infected malaria subjects
For healthy control group
Exclusion Criteria:
For P. vivax-infected malaria subjects
For healthy control group
Thirty (30) P. vivax-infected adults will be enrolled in Khun Han Hospital to receive 5 days or oral artesunate (4 mg/kg) and 15 mg/day of oral primaquine for 14 days
Drug: Primaquine
Sixty (60) P. vivax-infected adults will be enrolled in Khun Han Hospital to receive 5 days or oral artesunate (4 mg/kg) and the primaquine regimen (15 mg/day for 14 days) not given until 42 days after enrollment
Drug: Primaquine
Ten (10) age- and gender-matched controls will be enrolled for one day to obtain biological samples to be compared to the 2 intervention arms
radical cure dosing
Therapeutic efficacy of a radical cure course of primaquine for uncomplicated P. vivax infection
In subjects presenting with uncomplicated P. vivax infection, determine frequency of P. vivax recurrence throughout the study period after being administered a 14-day course of primaquine
Time frame: 6 months
Build a biorepository of prospectively collected blood and urine samples in P. vivax patients prior to relapse to analyze for hypnozoite biomarkers
At pre-determined time points, collect biological samples to be processed and stored for proteomic, metabolomic, genomic and transcriptomic markers of latent hypnozoites, allowing for comparisons of markers in those who did and those who did not relapse
Time frame: 6 months
Characterize the patterns of relapsing Southeast Asian P. vivax in infected subjects
Percentage of P. vivax relapse in subjects with uncomplicated P. vivax mono-infection in the 28 days following treatment with oral blood stage anti-malarial treatment with comparisons between those administered primaquine at enrollment and those who did not receive primaquine
Time frame: 28 days
Delineate relapse kinetics of P. vivax infection using molecular diagnostic methods,
At pre-determined time points starting at admission and prior to P. vivax relapse, compare limit of detection of recently emerged erythrocytic forms by blood smear, polymerase chain reaction (PCR) and ultra sensitive PCR
Time frame: 42 days
Determine percentage of P. vivax isolates resistant to antimalarial drugs used for treatment
Parasite growth inhibition as measured by concentration at which 50% of growth is inhibited (IC50) to antimalarial drug panel using pLDH ELISA techniques
Time frame: 6 months
Establish rates of P. vivax relapse versus new infection with vivax using molecular methods
Perform genome sequencing to determine genetic signatures of the vivax parasite, comparing initial infection with recurrences to identify relapse versus a new infection
Time frame: 6 months
Characterize the rate glucose 6-phosphate dehydrogenase (G6PD) deficiency of study population
Incidence of G6PD deficiency (\<30% activity) using quantitative spectrophotometry diagnostics
Time frame: 3 months
Characterize hepatic cytochrome P450 (CYP450) 2D6 enzyme genotypes and predicted phenotypes in this study population
Genotype CYP450 2D6 alleles in this study population and resultant predicted metabolism phenotypes using Activity Score A (AS-A)
Time frame: 1 day
Determine primaquine pharmacokinetics in this study population
Measure plasma concentrations of primaquine and its major metabolites at 0,2,4,8,10 and 24 hours after initial primaquine dose and calculate the area under the curve (AUC) for each subject
Time frame: 56 days
Determine primaquine pharmacokinetics in this study population
Measure urine concentrations of primaquine and its major metabolites at 0-4 hours, 4-10 hours and 10-24 hours after initial primaquine dose and calculate the area under the curve (AUC) for each subject
Time frame: 56 days
Assess impact of risk factors of travel and prior malaria history on P. vivax relapse kinetics
Determine number of days of travel to high malaria risk areas in 30 days prior to enrollment for each subject to compare with parasite genetic relatedness of initial and recurrent vivax infections
Time frame: 6 months
Measure rates of gametocyte carriage
Determine rate and duration of sexual stage infections based on light microscopy and molecular analyses (PCR) from samples drawn at enrollment and pre-determined time points over study period
Time frame: 6 months
Determine if humoral immunity contributes to protection against P. vivax recurrence
Measure antibody levels against vivax antigens merozoite surface protein-1 (MSP-1) and circumsporozoite protein (CSP) at Day 0,28,90 and 180 and compare to rate of P. vivax recurrence
Time frame: 6 months
This study is status unknown, as verified in Dec 2019. You cannot join it, but the record below documents what was studied.
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Armed Forces Research Institute of Medical Sciences, Thailand