Merozoite Surface Protein 1 Antibody Response in Asymptomatic Human Malaria Infection

NCT00761020 | Completed DMC

• 2 other identifiers: WRAIR 1490HSRRB Log#A-15136
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria

Keywords

Malaria; Diagnosis; Biomarker

Outcome Measures

Primary Outcomes (1)

• Subjects showing four-fold increase in antibody titer

  The focus of the statistical analysis will be to estimate (with 95% confidence limits) the sensitivity of Pf assay in the mefloquine and control arms. Sensitivity will be calculated as the number of subjects in each cohort who develop at least a four-fold increase in antibody titer from baseline (measured positives) divided by the number infected (true positives). The binomial test will used to test the null hypothesis that the sensitivity in the mefloquine arm is at 30% α(= 0.05; one-sided). The control group will serve as a check on the challenge. The study is not powered to statistically test for a difference in sensitivity between mefloquine and control arms. ELISA titer data will be log-transformed for all analyses. For each group, geometric mean anti-MSP-1 antibody titers with 95% confidence intervals will be determined by ELISA and tabulated at each time point which blood samples are taken for serology.

  1 year

Secondary Outcomes (1)

• Subjects showing Anti- Pf MSP-1 IgG antibody response

  1 year

Study Arms (2)

Mefloquine

EXPERIMENTAL

Mefloquine 250 mg orally daily x 3 days beginning 2 days prior to challenge and then weekly for 4 weeks post challenge.

Drug: Mefloquine

Control

SHAM COMPARATOR

Other: Control

Interventions

Mefloquine DRUG

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.

Also known as: Lariam

Mefloquine

Control OTHER

No Intervention

Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

Location

MeSH Terms

Conditions

Malaria; Disease

Interventions

Mefloquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• James Moon, MD

  Walter Reed Army Institute of Research (WRAIR)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 25, 2008
• First Posted: September 26, 2008
• Study Start: September 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

US (1)