- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01585077
Exposure of Naive and Pre-immune Subjects to P. Vivax Challenge (ChallengeIII)
Comparison of the Susceptibility of Naive and Pre-immune Volunteers to Infectious Challenge With Viable Plasmodium Vivax Sporozoites.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is a prospective controlled, blinded clinical trial, designed to establish the differences on infectivity of an infectious challenge with P. vivax sporozoites between human volunteers with and without history of malaria.
Study subjects
This study will require the involvement of two types of volunteers:
- Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for experimental infection of mosquitoes, who will be enrolled in the endemic area.
- Volunteers for infectious challenge Two other groups of volunteers will be exposed to mosquitoes infected with P. vivax sporozoites. A group of 7 people without previous exposure to malaria (naive) and another 12 people with a history of previous malaria infection (pre-immune).
Methodology
- Recruitment of infected patients Parasite donors will be recruited among P. vivax infected patients attending a diagnostic center in the endemic area.
- Infection of mosquitoes Blood from donors will be used to feed three days old mosquitoes by artificial membrane feeding technique. At day 7 a sample of mosquitoes will be examined to determine the degree of infection by dissection of the mosquito gut. On day 14, a small amount of mosquitoes with a good degree of infectivity will be used to infect challenged volunteers.
- Recruitment of pre-immune and naive volunteers Volunteers for the challenge will be recruited both in the city of Cali, non-endemic region, and in Buenaventura, a malaria endemic region, through various activities such as conferences, meetings and other means approved by the IRB like posters and flyers.
Infection of volunteers
The "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding window, wich will be covered by a mesh surface be placed against the volunteer's skin.
Follow Up
Volunteers will be educated about the signs and symptoms of malaria and they will have a daily telephone contact during the first 6 days.
Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily in order to establish the presence or absence of disease through thick blood smear and samples will be collected for retrospective real time PCR P. vivax.
From day 23 until day 31, volunteers will receive physical and laboratory evaluation every other day and will have daily telephone contact.
Once the patients present signs and symptoms of the disease curative treatment will be immediately provided, and 15 ml of blood will be drawn, which will be used for immune response assessment.
If the volunteers do not develop the disease during the follow-up period, on day 31 they will be given antimalarial treatment.
Treatment
Volunteers will be treated with antimalarial drugs approved by the Colombian Ministry of Social Protection: chloroquine (three (3) doses: 600 mg initially, followed by 450mg at 24, and 48 hours), associated with primaquine (30mg/día) for 14 days. All the volunteers will be asked to return two weeks after starting treatment for a thick blood smear test to ensure cure of malaria.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Valle del Cauca
-
Cali, Valle del Cauca, Colombia
- Malaria Vaccine and Drug development Center (MVDC)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Step 1:
- Age 15 to 60 years.
- Hemoglobin levels > 9g/dL.
- Presence of Current P. vivax infection.
- Absence of other Plasmodium species determined by thick blood smear and PCR.
- Blood parasite count of 0.1% or more.
- Absence of other acute or chronic diseases.
- Being able to sign an informed consent form.
Step 2:
- Healthy 18 to 45 years old man or non-pregnant women.
- To have the capacity to sign an informed consent in a free and voluntary way.
- To have an acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process.
- Obligatory use of adequate contraceptive method from beginning of recruitment and screening time up to three months after last immunization.
- Do not have chronic or acute diseases. These conditions will be determined by clinical history, physical exam and laboratory tests.
- To accept not traveling to malaria endemic areas during the clinical trial should
- To have telephone at home or mobile phone that permit permanent contact for follow up
- Being willing to participated during both steps of the clinical trial.
Exclusion Criteria:
Step 1:
- history of blood transfusion in the last six months.
- Pregnancy in women.
- Have received antimalarial treatment before the diagnosis.
Step 2:
- Pregnant or nursing women.
- History of moderate or severe insect, or food allergies.
- G-6PD deficiency or any Hb genetic defect.
- Symptoms, signs or data from laboratory test that suggests any systemic disorder like renal, hepatic, cardiovascular, pulmonary, psychiatric disorders or other illnesses that could interfere with results of clinical trial or could compromise the health of the volunteer.
- To have antibodies against hepatitis C, VIH, or hepatitis B superficial antigen and/or hepatitis B core antibodies.
- To have any abnormality in the parameters assessed by blood laboratory tests
- Presence or history of an auto-immune disease.
- History of surgical removal of the spleen (splenectomy).
- Use of medical treatment known to alter the immune system before 3 months to recruitment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Naive volunteers
Volunteers without previous exposure to malaria, and negative antibody titers (<1:20) against native protein of P. vivax.
|
All volunteers will receive one dose of 2-4 P. vivax infected mosquito bites.
All the mosquitoes will correspond to the same mosquito batch to make sure that all volunteers receive the same P. vivax strain.
|
Experimental: Pre-immune volunteers
Volunteers with previous exposure to malaria, and positive antibody titers against native protein of P. vivax
|
All volunteers will receive one dose of 2-4 P. vivax infected mosquito bites.
All the mosquitoes will correspond to the same mosquito batch to make sure that all volunteers receive the same P. vivax strain.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pre-patent period onset
Time Frame: Two months after the challenge
|
begining at day 7 after mosquito bites exposure, both groups of volunteers will be evaluated with dayly Thick blood smear to compare the malaria onset between the pre-immune and naive groups.
|
Two months after the challenge
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immune response
Time Frame: Two months after the malaria challenge
|
Malaria signs and symptoms will be assessed to stablish severity and frequency of appearence in both groups: Pre-immune and naive. Blood sample will be taken at the end of the study to determine the differences in celular and humoral immune responses in both study groups. |
Two months after the malaria challenge
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sócrates Herrera, MD, Malaria Vaccine and Drug Development Center
Publications and helpful links
General Publications
- Herrera S, Solarte Y, Jordan-Villegas A, Echavarria JF, Rocha L, Palacios R, Ramirez O, Velez JD, Epstein JE, Richie TL, Arevalo-Herrera M. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):4-11. doi: 10.4269/ajtmh.2011.09-0498.
- Herrera S, Fernandez O, Manzano MR, Murrain B, Vergara J, Blanco P, Palacios R, Velez JD, Epstein JE, Chen-Mok M, Reed ZH, Arevalo-Herrera M. Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. Am J Trop Med Hyg. 2009 Nov;81(5):740-6. doi: 10.4269/ajtmh.2009.09-0194.
- Arevalo-Herrera M, Forero-Pena DA, Rubiano K, Gomez-Hincapie J, Martinez NL, Lopez-Perez M, Castellanos A, Cespedes N, Palacios R, Onate JM, Herrera S. Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers. PLoS One. 2014 Jun 25;9(6):e99754. doi: 10.1371/journal.pone.0099754. eCollection 2014.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CIV - 08 - 102010
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on P. vivax infected mosquito bites
-
University of OxfordMahidol UniversityRecruiting
-
University of OxfordNational Health and Medical Research Council, Australia; Burnet Institute; Agency...Recruiting
-
University of OxfordActive, not recruiting
-
University of NottinghamNorgineCompletedFunctional Constipation | Irritable Bowel Syndrome Characterized by ConstipationUnited Kingdom
-
U.S. Army Medical Research and Development CommandGlaxoSmithKline; United States Department of Defense; Walter Reed Army Institute... and other collaboratorsCompletedMalaria | Plasmodium VivaxUnited States
-
Malaria Vaccine and Drug Development CenterNational Heart, Lung, and Blood Institute (NHLBI); Asoclinic Inmunología Ltda.Completed
-
Radboud University Medical CenterCompletedP. Falciparum MalariaNetherlands
-
Centers for Disease Control and PreventionColumbia University; United States Agency for International Development (USAID)Completed
-
Radboud University Medical CenterErasmus Medical Center; The PATH Malaria Vaccine Initiative (MVI); Havenzieke...CompletedPlasmodium Falciparum | Malaria,Falciparum | Plasmodium Berghei | Controlled Human Malaria Infection (CHMI)Netherlands
-
State Key Laboratory of Respiratory DiseaseCAS Lamvac Biotech Co., Ltd.Recruiting