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Study to Investigate the Induction of an Protective Immune Response to Malaria

Primary Purpose

Falciparum Malaria

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
exposure to malaria sporozoites
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Falciparum Malaria focused on measuring Falciparum, Plasmodium, Malaria

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age > 18 and < 45 years healthy volunteers (males or females).
  • General good health based on history and clinical examination.
  • All volunteers have to sign the informed consent form.
  • Negative pregnancy test.
  • Use of adequate contraception for females
  • Reachable by phone during the whole study period.
  • Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the trial

Exclusion Criteria:

  • History of malaria or residence in malaria endemic areas within the past six months.
  • Positive serology for P. falciparum
  • Previously participated in any malaria vaccine study
  • Symptoms, physical signs and laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the study results or compromise the health of the volunteers.
  • Cardiovascular risk >10% according to European guidelines, taking into account sex, age, cholesterol, weight, smoking habits, blood pressure, diabetes
  • Any laboratory abnormalities on screened blood samples beyond the normal range, as defined at UMC St Radboud. Positive HIV, HBV or HCV tests.
  • Volunteers should not be enrolled in any other clinical trial during the whole trial period.
  • Volunteers should not receive chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the three months preceding the screening visit or during the study period.
  • Pregnant or lactating women.
  • Volunteers unable to give written informed consent.
  • Volunteers unable to be closely followed for social, geographic or psychological reasons.
  • Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study.
  • Known hypersensitivity for anti-malaria drugs
  • Volunteers are not allowed to travel to malaria endemic countries during the study period.

Sites / Locations

  • Radboud University Nijmegen Medical Centre

Outcomes

Primary Outcome Measures

A significant difference in time of thick smear positivity between exposed and control groups
A significant difference in parasitemia as measured by 18S Pf NASBA between exposed and control group
A significant difference in kinetics of parasitemia between exposed and control groups as measured by 18S Pf NASBA.
A difference in occurrence or height of fever between exposed and control groups.

Secondary Outcome Measures

Significant differences in immune response between exposed and control volunteers (including NK-cell reactivity, TLR reactivity and regulatory T-cell reactivity)
Significant differences in the outcome of in vitro functional malaria assays between exposed and control volunteers
Significant differences in cellular reactivity against Pf antigens
Significant differences in parasite VAR gene expression during infection
The identification of immune mechanisms that correlate with protection
6. The identification of potential vaccine candidates that correlate with protection

Full Information

First Posted
February 28, 2007
Last Updated
August 15, 2007
Sponsor
Radboud University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00442377
Brief Title
Study to Investigate the Induction of an Protective Immune Response to Malaria
Official Title
Exposure of Human Volunteers to Live Malaria Sporozoites Under Chloroquine Prophylaxis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2007
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Radboud University Medical Center

4. Oversight

5. Study Description

Brief Summary
The objective of the study is to induce a protective immune response against malaria in healthy human volunteers. The different parts of the immune response will then be studied.
Detailed Description
Efforts to develop vaccines against malaria still represent a substantial focus of current research activities. Factors that have hampered the development of a subunit vaccine include the complexity of the malaria life cycle, the wide variety of immune response induced by the malaria parasite, and an incomplete knowledge of protective immunity. This study is therefore aimed at inducing protective immunity against malaria in 15 healthy volunteers. Volunteers will be exposed to the bites of infectious mosquitoes 3 times with live P. falciparum sporozoites under chloroquine prophylaxis. Challenge with infected mosquitoes will be given after stopping chloroquine prophylaxis. Five volunteers will form a control group; they will be exposed to non-infectious mosquitoes under chloroquine prophylaxis. Endpoints include the time and height of parasitemia after challenge, the development of fever and immunological parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Falciparum Malaria
Keywords
Falciparum, Plasmodium, Malaria

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Procedure
Intervention Name(s)
exposure to malaria sporozoites
Primary Outcome Measure Information:
Title
A significant difference in time of thick smear positivity between exposed and control groups
Title
A significant difference in parasitemia as measured by 18S Pf NASBA between exposed and control group
Title
A significant difference in kinetics of parasitemia between exposed and control groups as measured by 18S Pf NASBA.
Title
A difference in occurrence or height of fever between exposed and control groups.
Secondary Outcome Measure Information:
Title
Significant differences in immune response between exposed and control volunteers (including NK-cell reactivity, TLR reactivity and regulatory T-cell reactivity)
Title
Significant differences in the outcome of in vitro functional malaria assays between exposed and control volunteers
Title
Significant differences in cellular reactivity against Pf antigens
Title
Significant differences in parasite VAR gene expression during infection
Title
The identification of immune mechanisms that correlate with protection
Title
6. The identification of potential vaccine candidates that correlate with protection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age > 18 and < 45 years healthy volunteers (males or females). General good health based on history and clinical examination. All volunteers have to sign the informed consent form. Negative pregnancy test. Use of adequate contraception for females Reachable by phone during the whole study period. Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the trial Exclusion Criteria: History of malaria or residence in malaria endemic areas within the past six months. Positive serology for P. falciparum Previously participated in any malaria vaccine study Symptoms, physical signs and laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the study results or compromise the health of the volunteers. Cardiovascular risk >10% according to European guidelines, taking into account sex, age, cholesterol, weight, smoking habits, blood pressure, diabetes Any laboratory abnormalities on screened blood samples beyond the normal range, as defined at UMC St Radboud. Positive HIV, HBV or HCV tests. Volunteers should not be enrolled in any other clinical trial during the whole trial period. Volunteers should not receive chronic medication, especially immunosuppressive agents (steroids, immunomodulating or immunosuppressive drugs) during the three months preceding the screening visit or during the study period. Pregnant or lactating women. Volunteers unable to give written informed consent. Volunteers unable to be closely followed for social, geographic or psychological reasons. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study. Known hypersensitivity for anti-malaria drugs Volunteers are not allowed to travel to malaria endemic countries during the study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Sauerwein, Prof
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
28081133
Citation
Coffeng LE, Hermsen CC, Sauerwein RW, de Vlas SJ. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection. PLoS Comput Biol. 2017 Jan 12;13(1):e1005255. doi: 10.1371/journal.pcbi.1005255. eCollection 2017 Jan.
Results Reference
derived
PubMed Identifier
19641203
Citation
Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
Results Reference
derived

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Study to Investigate the Induction of an Protective Immune Response to Malaria

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