Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001238460
Ethics application status
Approved
Date submitted
18/08/2016
Date registered
6/09/2016
Date last updated
7/02/2020
Date data sharing statement initially provided
7/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Advanced Medical Imaging in Subpatent Malaria: a pilot study
Scientific title
Advanced medical imaging in healthy volunteers with induced blood stage model subpatent malaria infection: a prospective observational pilot study to assess parasite biodistribution and activity using 18F FDG PET/MRI
Secondary ID [1] 289956 0
Nil Known
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Parasite sequestration in experimental subpatent malaria infection induced by the induced blood stage malaria human challenge model. 299942 0
Condition category
Condition code
Infection 299843 299843 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will be recruited from independent clinical trials that involve induced blood stage malaria challenge. As part of these independent clinics trials participants are inoculated with a low dose of malaria which is subsequently closely monitored in the community for 8 to 10 days prior to treatment. Based on the level of malaria detected in these trials participants are then admitted to the trial unit (confinement period) for administration of an anti-malarial agent to treat the induced infection and determine the efficacy of this agent. If participants are recruited into this study they will have an observational PET/MRI scan. The timing of this scan will work in accordance to the malaria inoculation schedule of the independent clinical trial. Participants will receive a whole body PET/MRI scan and dedicated brain MRI within approximately one week prior to inoculation and on one to two days prior to confinement with peak parasitaemia post inoculation. Scans will be performed on the Biograph mMR PET/MRI system after the intravenous infusion of the standard radiotracer 2-(18F) fluor-deoxy-D-glucose(FDG) (18F FDG) and MAGNETOM Prisma 3T MRI system. Collected images will be reviewed and reported by experienced radiologists specialising in MRI and nuclear medicine reporting. Quantification of 18F FDG uptake measurements will be established for intra-individual scans using Patlak model analysis and semi quantitative SUV measurement with reference to an 18F FDG external control
Intervention code [1] 295645 0
Diagnosis / Prognosis
Comparator / control treatment
Pre inoculation imaging will serve as a control for post inoculation imaging in this prospective observational study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299324 0
The primary objective of the study is to assess the application of whole body 18F FDG-PET/MRI in describing the parasite biodistribution and biomass in subpatent malaria. This is a hypothesis pilot investigation expected to have predominately descriptive outcomes.

Primary Outcome 1: Intra-individual PET tracer uptake changes in regions of interest post malaria inoculation
Timepoint [1] 299324 0
Primary outcome 1 Timepoint: baseline and estimated 7-9 days following low dose malaria inoculation.

Review of the peak parasitaemia data from previous blood stage malaria challenge studies has found that P. falciparum challenge study participants undergo confinement on Day 8 after inoculation, and P. vivax challenge study participants undergo confinement on Day 10 after inoculation. This is related to the size of the inoculum and characteristics of the malaria species itself. As a result, in order to perform the PET/MRI imaging at close to peak parasitaemia, it is expected that this imaging will take place on Day 7 after inoculation for P. falciparum and Day 9 after inoculation for P. vivax. Exact day numbers have not been provided to accommodate for the possibility of biological variability in infection (although this has not occurred historically.)
Primary outcome [2] 299325 0
Primary Outcome 2: Intra-individual MRI imaging changes in regions of interest post malaria inoculation
Timepoint [2] 299325 0
Primary outcome 2 Timepoint: baseline and estimated 7-9 days following low dose malaria inoculation.

Review of the peak parasitaemia data from previous blood stage malaria challenge studies has found that P. falciparum challenge study participants undergo confinement on Day 8 after inoculation, and P. vivax challenge study participants undergo confinement on Day 10 after inoculation. This is related to the size of the inoculum and characteristics of the malaria species itself. As a result, in order to perform the PET/MRI imaging at close to peak parasitaemia, it is expected that this imaging will take place on Day 7 after inoculation for P. falciparum and Day 9 after inoculation for P. vivax. Exact day numbers have not been provided to accommodate for the possibility of biological variability in infection (although this has not occurred historically.)
Secondary outcome [1] 326839 0
Secondary Outcome 1: Intra-individual differences in PET tracer uptake and MRI imaging changes in regions of interest to describe the relative burden of organ specific sequestration
Timepoint [1] 326839 0
Secondary Outcome 1 Timepoint: estimated 7-9 days following low dose malaria inoculation.
The intraindividual differences will be derived from comparing pre and post inoculation imaging in participants. That is, imaging before inoculation, and at estimated 7-9 days following low dose malaria inoculation.
Secondary outcome [2] 326840 0
Secondary Outcome 2: Inter-individual differences in PET tracer uptake and MRI imaging changes in regions of interest with respect to Plasmodium species challenge and parasite load
Timepoint [2] 326840 0
Secondary Outcome 2 Timepoint: estimated 7-9 days following low dose malaria inoculation.
The intraindividual differences will be derived from comparing pre and post inoculation imaging in participants. That is, imaging before inoculation, and at estimated 7-9 days following low dose malaria inoculation.
Secondary outcome [3] 326841 0
Secondary Outcome 3: The impact of early malaria infection on glucose metabolism will be evaluated in assessing each of the above outcomes.
18F FDG is essentially glucose that can be tracked through the body following administration using PET imaging. Therefore the PET/MRI imaging itself will provide the information about glucose metabolism. Finger prick blood glucose monitoring will be used prior to imaging to determine the baseline blood glucose, and all participants are required to have a normal fasted blood glucose measurement (as per inclusion criteria.)
Timepoint [3] 326841 0
Secondary Outcome 3 Timepoint: estimated 7-9 days following low dose malaria inoculation.
18F FDG is essentially glucose that can be tracked through the body following administration using PET imaging. Therefore the PET/MRI imaging itself will provide the information about glucose metabolism. Finger prick blood glucose monitoring will be used prior to imaging to determine the baseline blood glucose, and all participants are required to have a normal fasted blood glucose measurement (as per inclusion criteria.)

Eligibility
Key inclusion criteria
*Provide signed and dated informed consent form
*Able to lie supine and still for duration of image acquisition
*Participating in induced blood stage malaria human challenge model study
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Known allergic reactions to components of the study radiotracer 18F FDG
*Fasted blood glucose elevated above the normal range (BSL >6.0mmol/L)
*Failure to meet/provide the standard MRI checklist requirements
*Claustrophobia precluding image acquisition
*Significant previous radiation exposure as defined (lifetime exposure):
a. Any fluoroscopic imaging (e.g. coronary angiography)
b. Any nuclear medicine imaging (e.g. myocardial perfusion scan)
c Greater than one previous CT scan
d. Note: previous plain film X-rays and mammography are acceptable

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a pilot investigation to assess the application of functional nuclear medicine in
subpatent malaria. The population will comprise of approximately eight adult participants. This population size has been estimated based on the clinical experience of the subinvestigators.
It is expected that this study will be hypothesis generating.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/10/2016
Actual
10/02/2017
Date of last participant enrolment
Anticipated
Actual
16/03/2017
Date of last data collection
Anticipated
Actual
13/04/2017
Sample size
Target
8
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 6497 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 14061 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 294335 0
Other Collaborative groups
Name [1] 294335 0
Herston Imaging Research Facility(HIRF): Seed Funding Grant
Country [1] 294335 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR-Berghofer Medical Research Institute
Address
300 Herston Road, Herston Queensland 4006
Country
Australia
Secondary sponsor category [1] 293172 0
None
Name [1] 293172 0
Address [1] 293172 0
Country [1] 293172 0
Other collaborator category [1] 279165 0
Hospital
Name [1] 279165 0
Department of Nuclear Medicine, Royal Brisbane and Women’s Hospital
Address [1] 279165 0
Royal Brisbane and Women’s Hospital, Herston Queensland 4029
Country [1] 279165 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295756 0
QIMR Berghofer Medical Research Institute HREC
Ethics committee address [1] 295756 0
Ethics committee country [1] 295756 0
Australia
Date submitted for ethics approval [1] 295756 0
14/10/2016
Approval date [1] 295756 0
02/12/2016
Ethics approval number [1] 295756 0
P2261

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68342 0
Prof James McCarthy
Address 68342 0
Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute
300 Herston Road Herston, Queensland 4006
Country 68342 0
Australia
Phone 68342 0
+617 3845 3636
Fax 68342 0
Email 68342 0
[email protected]
Contact person for public queries
Name 68343 0
John Woodford
Address 68343 0
Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute
300 Herston Road Herston, Queensland 4006
Country 68343 0
Australia
Phone 68343 0
+617 3646 8111
Fax 68343 0
Email 68343 0
[email protected]
Contact person for scientific queries
Name 68344 0
John Woodford
Address 68344 0
Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute
300 Herston Road Herston, Queensland 4006
Country 68344 0
Australia
Phone 68344 0
+617 3646 8111
Fax 68344 0
Email 68344 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIPositron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study2021https://doi.org/10.1371/journal.pmed.1003567
N.B. These documents automatically identified may not have been verified by the study sponsor.