Immune response in a human malaria challenge system.

Phase 2

Completed

• Conditions: Malaria; Infection - Other infectious diseases

• Registration Number: ACTRN12611001203943
• Lead Sponsor: Queensland Institute of Medical Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-23
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1) Volunteers will be males, aged between 18 and 45 years who do not live alone (from Day 1 until at least the end of the antimalarial drug treatment).
2) Volunteers must have a BMI within the range 18–30.
3) Volunteers must understand the procedures involved and agree to participate in the study by giving fully informed, written consent.
4) Be contactable and available for the duration of the trial (maximum of 4 weeks)
5) Volunteers must be non-smokers and in good health, as assessed during pre-study medical examination and by review of screening results.
6) Good peripheral venous access

Exclusion Criteria

1) History of malaria
2) Travelled to or lived (>2 weeks) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study
3) Has evidence of increased cardiovascular disease risk (defined as >10%, 5 year risk) as determined by the method of Gaziano et al., (15). Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), reported diabetes status and blood pressure
4) History of splenectomy
5) History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
6) Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non spreadable skin cancers such as basal cell and squamous cell carcinoma
7) Known inherited genetic anomaly (known as cytogenetic disorders) e.g., Down’s syndrome
8) Volunteers wishing to be able to donate blood to the ARCBS in the future
9) Presence of retinal or visual field changes either attributable to 4-aminoquinoline compounds or to any other etiology
10) The volunteer has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis
11) The volunteer has been hospitalized within the past 5 years prior to enrollment for psychiatric illness, history of suicide attempt or confinement for danger to self or others
12) The volunteer is receiving psychiatric drugs. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator’s discretion.
13) Known pre-existing prolongation of the QTc interval
14) Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical condition known to prolong the QTc interval, e.g. volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
15) Recent or current therapy with an antibiotic or drug with potential antimalarial activity (tetracycline, azthromycin, clindamycin, hydroxychloroquine etc.)
16) Known hypersensitivity to sulfa drugs
17) Concomitant use of any drug which is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine) OR drugs that are known to prolong the QTc interval, e.g. antiarrhythmics of classes IA and III, neuroleptics, antidepressant agents, certain antibiotics (including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents), certain nonsedating antihistamines (terfenadine, astemizole), cisapride.
18) Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamic-pituitary-adrenal axis suppression such as 1mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 µg

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of the gene expression profiles of whole blood and T cell subsets before and after experimental challenge with a low dose of Plasmodium falciparum blood stage parasites.[Using mass array analysis to compare gene expression profiles of whole blood and T cell subsets before and 28 days after experimental challenge with a low dose of Plasmodium falciparum blood stage parasites.]

Secondary Outcome Measures

Name	Time	Method
Identification of molecular signatures that predict disease outcome.[Compare signatures obtained in expression profile studies 28 days after challenge to those seen in natural malaria infection.];Investigation of gametocyte maturation during early blood stage infection.[Documenting transcription levels of gametocyte-specific genes between days 7 and 14.]