Merozoite Surface Protein 1 Antibody Response in Asymptomatic Human Malaria Infection - Full Text View

Purpose

The main purpose of this trial is to study whether a certain blood test can reliably identify the presence of malaria in people who have been infected with, but who do not have symptoms of malaria.

Condition	Intervention	Phase
Malaria	Other: Mefloquine and Control Cohort	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Analysis of Anti-Plasmodium Falciparum Merozoite Surface Protein 1 Antigen Specific Antibodies in a Human Malaria Challenge Using Mefloquine Prophylaxis to Confirm Assay Sensitivity and Establish Key Antibody Kinetic Parameters

Resource links provided by NLM:

MedlinePlus related topics: Malaria

Drug Information available for: Mefloquine hydrochloride

U.S. FDA Resources

Further study details as provided by Walter Reed Army Institute of Research (WRAIR):

Primary Outcome Measures:

The number of subjects in each group who develop at least a four-fold increase in Anti-Plasmodium falciparum MSP-1 IgG antibody titer at any time point from baseline divided by the number infected [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Specific levels and patterns of Anti-Pf MSP-1 IgG antibody response, both in individual subjects and means across the study population [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	31
Study Start Date:	September 2008
Study Completion Date:	December 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: Mefloquine Mefloquine 250 mg orally daily x 3 days beginning 2 days prior to challenge and then weekly for 4 weeks post challenge (n=19 to 25)	Other: Mefloquine and Control Cohort To determine the seroconversion rate (sensitivity) to Plasmodium falciparum Merozoite Surface Protein 1 (Pf MSP-1) antigen by ELISA assay in the infectivity control and mefloquine cohorts as part of a larger project to support the qualification of anti-MSP-1 antigen-specific antibody assays as valid surrogate endpoints for malaria infection.
No Intervention: Control Sporozoite infectivity control; no prophylaxis (n=6). Infectivity controls will undergo primary sporozoite challenge in parallel with Cohort 1. Up to 9 individuals will be recruited (6, plus up to 3 alternates) to ensure that the goal of 6 enrollments is achieved.	Other: Mefloquine and Control Cohort To determine the seroconversion rate (sensitivity) to Plasmodium falciparum Merozoite Surface Protein 1 (Pf MSP-1) antigen by ELISA assay in the infectivity control and mefloquine cohorts as part of a larger project to support the qualification of anti-MSP-1 antigen-specific antibody assays as valid surrogate endpoints for malaria infection.

Detailed Description:

In this study, two groups of volunteers will be exposed to malaria through the bites of infected mosquitoes. In one group, volunteers will be given several doses of a drug called mefloquine, known to prevent the development of malaria symptoms. The other group will not be treated with any drug that could prevent symptoms or infection. After exposure, both groups will be monitored for a period of approximately 6 months to see if they develop symptoms of malaria. Any subjects who do so will be treated with appropriate medications. Subjects in both groups will have their blood checked regularly during this period for the presence of a certain malaria antibody called Merozoite Surface Protein 1, or Anti-MSP-1 for short, using a special blood test (also known as an assay). At the completion of the study, the results of all assays will be analyzed to determine if this test can be used to diagnose malaria infection in persons without symptoms.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

A male or non-pregnant, non-lactating female 18 to 55 years of age (inclusive) at the time of screening
Written informed consent obtained from the participant before screening procedures
Free of clinically significant health problems as established by medical history and clinical examination before entering into the study
Available to participate for duration of study (approximately 6 months, not including screening period)
If the participant is female, she must be of non-childbearing potential, (i.e., either surgically sterilized or one year post-menopausal) or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®) during this study, have a negative pregnancy test at the time of enrollment, and must agree to continue such precautions for at least two months after completion of the malaria challenge if part of the control cohort, or for three months after the final mefloquine dose is taken if part of the mefloquine cohort.
Prior to entry into this study, participants must score at least 80% correct on a short multiple-choice quiz that assesses their understanding of this study. If they do not score 80% on the initial quiz, the protocol information will be reviewed with them to ensure comprehension and they will have the opportunity to retest (using the same test). Participants who fail the Comprehension Assessment for the second time will not be enrolled.

Exclusion Criteria:

History of malaria
Travel to a malarious country within the previous 12 months
History of participation in a study in which potential exposure to malaria or vaccination against malaria occurred.
Planned travel to malarious areas during the study period
History of malaria chemoprophylaxis within 60 days prior to time of study entry
Recent (defined as any use within 30 days of study entry) or chronic use (defined as more than 14 days of use within 60 days of study entry) of antibiotics with anti-malarial effects (e.g., tetracyclines for dermatologic patients, clindamycin for soft tissue and bone infections, sulfa for recurrent urinary tract infections, etc.)
Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of study entry. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
Administration of immunoglobulins and/or any blood products within the three months preceding study entry or planned administration during the study period
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
Personal medical histories including the following diagnoses: systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, vasculitis, and multiple sclerosis
Elevated serum creatinine, defined in this study as greater than or equal to 1.7 mg/dL in males and 1.4 mg/dL in females
Elevated transaminases, defined in this study as greater than twice the upper limit of the normal range (>2 ULN)
Significant unexplained anemia: hematocrit < 35%
History of sickle cell disease or sickle cell trait
Seropositive for hepatitis B surface antigen or hepatitis C antibody
Hepatomegaly, right upper quadrant abdominal pain or tenderness
History of splenectomy
Pregnant or lactating female, or female who intends to become pregnant during the study
Chronic or active neurologic disorders including seizures, excluding a single febrile seizure as a child
History of a neuropsychiatric disorder (anxiety, depression, psychosis, schizophrenia, PTSD, etc.)
Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV (Diagnostic and Statistical Manual of Mental Disorders- 4th edition)
Chronic or active illicit and/or intravenous drug use
History of severe anaphylactic reactions to mosquito bites
History of allergy to mefloquine
History of intolerance to mefloquine
History of psoriasis (given its interaction with chloroquine)
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761020

Locations

United States, Maryland
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States, 20910

Sponsors and Collaborators

Walter Reed Army Institute of Research (WRAIR)

Investigators

Principal Investigator:

James Moon, MD

Walter Reed Army Institute of Research (WRAIR)

More Information

No publications provided

Responsible Party:	James Moon, Walter Reed Army Institute of Research
ClinicalTrials.gov Identifier:	NCT00761020 History of Changes
Other Study ID Numbers:	WRAIR 1490, HSRRB Log#A-15136
Study First Received:	September 25, 2008
Last Updated:	June 2, 2010
Health Authority:	United States: Federal Government

Keywords provided by Walter Reed Army Institute of Research (WRAIR):

Malaria
Diagnosis
Biomarker

Additional relevant MeSH terms:

Malaria
Protozoan Infections
Parasitic Diseases
Antibodies
Mefloquine
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013