Biomarkers of P. Vivax Relapse

NCT04228315 | Unknown

• 1 other identifier: WR2643
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria; Vivax Malaria; Relapse; CYP2D6 Polymorphism

Keywords

primaquine; biomarker; hypnozoite; efficacy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  6 months

Secondary Outcomes (11)

• Characterize the patterns of relapsing Southeast Asian P. vivax in infected subjects

  28 days

• Delineate relapse kinetics of P. vivax infection using molecular diagnostic methods,

  42 days

• Determine percentage of P. vivax isolates resistant to antimalarial drugs used for treatment

  6 months

• Establish rates of P. vivax relapse versus new infection with vivax using molecular methods

  6 months

• Characterize the rate glucose 6-phosphate dehydrogenase (G6PD) deficiency of study population

  3 months

Study Arms (3)

Early primaquine group

EXPERIMENTAL

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

Delayed Primaquine group

ACTIVE COMPARATOR

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

Healthy control group

NO INTERVENTION

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

Interventions

Primaquine DRUG

radical cure dosing

Delayed Primaquine group; Early primaquine group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For P. vivax-infected malaria subjects
• Are a Thai male or non-pregnant/non-lactating female aged at least 18 years and are able to fluently speak and understand Thai
• Willingness to participate in the study as evidenced by witnessed, signed informed consent from the subject (written or thumb print)
• Have P. vivax malaria mono-infection as determined by blood smear, with a parasitemia range of 100-400,000 parasites/microliter
• Are available to stay in a controlled setting for the first 28 days of this study to minimize exposure to mosquitoes and available for follow-up for anticipated study duration
• Resides in Sisaket or Ubon Ratchathani Province
• Are of normal (non-deficient or \>30% activity) G6PD phenotype as defined by WHO
• Agree to not seek outside medical care prior to contacting the Armed Forces Research Institute of Medical Sciences (AFRIMS) study team if a fever develops during study participation (approximately 180 days), unless emergency medical care is required
• For healthy control group
• Are a Thai male or non-pregnant/non-lactating female aged at least 18 years and are able to fluently speak and understand Thai
• Willingness to participate in the study as evidenced by witnessed, signed informed consent from the subject (written or thumb print)
• Free of malaria and other significant health problems as established by medical history, laboratory assessment and clinical examination by clinical investigator
• Normal (non-deficient or \> 30% activity) G6PD phenotype as defined by World Health Organization (WHO)
• Resides in Sisaket or Ubon Ratchathani Province

You may not qualify if:

• For P. vivax-infected malaria subjects
• Have an allergic reaction to artesunate or primaquine
• History of anti-malarial drug use within the past 28 days
• Have symptoms of severe malaria needing urgent treatment, such as serious vomiting, unable to eat or drink, prostration, or other signs/symptoms of concern to the doctors
• Are a pregnant or lactating female, or female of childbearing age, up to 50 years of age or otherwise individually assessed for childbearing potential, who does not agree to use an acceptable form of contraception (e.g. pills or injectable) during this study and for 1 month after study completion
• Chronic use of medications known to cause drug interactions with primaquine or CYP450 2D6 (selective serotonin reuptake inhibitors (SSRIs) or other medications used for psychological conditions, as well as antihistamines, antihypertensives, codeine)
• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study
• For healthy control group
• Has history of malaria infection in the past 10 years
• Positive for any Plasmodium species by blood smear or PCR at time of screening
• Pregnant or lactating female
• G6PD deficient as defined by WHO
• Any other significant finding that in the opinion of the investigator would increase the risk of compromising the validity of being a control (eg., chronic daily chewing of betel nut (may impact saliva assays) or menstruating females (whereby urine collections may have blood and impact assay results), etc.

Sponsors & Collaborators

• Armed Forces Research Institute of Medical Sciences, Thailand: lead
• University of North Carolina, Chapel Hill: collaborator

Study Sites (1)

Khun Han Hospital

Khun Han, Thailand

RECRUITING

MeSH Terms

Conditions

Malaria; Malaria, Vivax; Recurrence

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Norman Waters, PhD

  Armed Forces Research Institute of Medical Sciences, Thailand

  STUDY DIRECTOR

• Michele Spring, MD

  Armed Forces Research Institute of Medical Sciences, Thailand

  PRINCIPAL INVESTIGATOR

• Ladaporn Bodhidatta, MD

  Armed Forces Research Institute of Medical Sciences, Thailand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele D Spring, MD

CONTACT

+66(0)2696-2700; michele.spring.ctr@afrims.org

Norman Waters, PhD

CONTACT

+66-(0)81 902 6756; Norman.Waters.mil@afrims.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The clinical study is a two arm, randomized, open-label treatment study of Thai adults with acute infection with P. vivax. All subjects will be treated with a short acting oral antimalarial, artesunate, to eradicate P. vivax malaria from the bloodstream. Radical cure with primaquine (15 mg/ day for 14 days) to eliminate the relapsing hypnozoite of P. vivax will be given at different times, depending on this study arm. Ten healthy controls will also be enrolled for 1 day to provide baseline samples.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 14, 2020
• Study Start: November 19, 2019
• Primary Completion: June 30, 2021
• Study Completion: December 31, 2024
• Last Updated: January 14, 2020

Record last verified: 2019-12

Locations

TH (1)