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Trial registered on ANZCTR


Registration number
ACTRN12615001126505p
Ethics application status
Submitted, not yet approved
Date submitted
14/10/2015
Date registered
26/10/2015
Date last updated
26/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study to examine the persistence and immunogenicity of Plasmodium falciparum 7G8 blood stage parasites following commencement of doxycycline chemoprophylaxis
Scientific title
A pilot study to examine the persistence and immunogenicity of Plasmodium falciparum 7G8 blood stage parasites following commencement of doxycycline chemoprophylaxis in healthy male adults
Secondary ID [1] 287668 0
Nil
Universal Trial Number (UTN)
Not applicable
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 296500 0
Condition category
Condition code
Infection 296757 296757 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Volunteers will be inoculated intravenously on Day 0 of the study with 3 x 10^6 purified human red blood cells infected with Plasmodium falciparum 7G8. One hour after inoculation they will commence doxycycline treatment which will be administered under direct supervision (in the study clinic) as a single capsule (100mg of doxycycline) daily for 7 days. This will be undertaken in one group (n=3)..

Blood will be drawn at set time points: every day from D1-D8 and every four days after that until D28, to measure parasite densities in the blood using quantitative PCR. If there is any evidence of a developing malaria infection, the individual will immediately commence standard anti-malarial treatment with Riamet.

Duration and dosage of Riamet (if required) Riamet tablets: Artemether (20mg) and Lumefantrine (120mg): 4 tablets orally as a single dose twice a day with fatty food at time 0, 8, 24, 36, 48 and 60 hours, making a total of 24 tablets in 6 doses. These doses will be administered under direct supervision in the study clinic.
Intervention code [1] 293057 0
Prevention
Intervention code [2] 293058 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296368 0
Parasite levels in the blood will be assessed by a sensitive molecular detection method (quantitative PCR) and microscopy to examine the persistence of the parasite following commencement of doxycycline treatment.
Timepoint [1] 296368 0
Active monitoring of parasite levels in the blood every day from D1-D8 and every four days after that until D28.
Primary outcome [2] 296369 0
To characterize the immunogenicity of P. falciparum 7G8 blood stage parasites following commencement of doxycycline chemoprophylaxis.

This will be assessed by implementing different immunological assays including flow cytometry and ELISAs.
Timepoint [2] 296369 0
Comparing antibody and T cell responses at day 0 with responses at Days 8, 16, 28 and 90
Secondary outcome [1] 318277 0
To assess the safety and tolerability of the P. falciparum 7G8 blood stage parasites.

This will be assessed by:
1. documenting the occurrence, severity and duration of inoculum-related solicited symptoms during the study period.
2. documenting the occurrence, severity and duration of inoculum-related unsolicited symptoms, abnormal physical findings and abnormal laboratory values during the study period
3. documenting the occurrence, severity and duration of inoculum-related serious adverse events during the study period.

These assessments will be carried out at each visit during the physical examination and medical history.
Timepoint [1] 318277 0
Active monitoring daily from inoculation (ie Day 0) until D8, and then every 4 days until D28. The final visit on Day 90. Passive monitoring (ie participants contacting and reporting any adverse events to study staff outside of scheduled visits) from Day 0 to Day 90

Eligibility
Key inclusion criteria
1. Volunteers will be males, aged 18-50 years of age who do not live alone for the duration of the study.
2. Volunteers must have a BMI within the range of 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 their study schedule (maximum of 3 months)
5. Volunteers must be non-smokers or smoke less than or equal to 5 cigarettes/day and in good health, as assessed during pre-study medical examination and by review of screening results
6. Good peripheral venous access
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has increased cardiovascular disease risk (defined as greater than 10%, 5 yr risk) as determined by the method of Gaziano et al 2008. Risk factors include: sex, age, systolic blood pressure, smoking status, body mass index (BMI, kg/mm2), and reported diabetes status and blood pressure.
2. History of splenectomy
3. History of severe allergic reaction, anaphylaxis or convulsion following any vaccination, infusion or treatment with anti-malarial drugs artemether and/or lumefantrine.
4. Presence of current or suspected 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, obsessive compulsive disorder, myasthenia gravis, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
5. Known inherited genetic anomaly (known as cytogenic disorders) eg Down’s syndrome.
6. Individuals wishing to donate blood to the Australian Red Cross Blood Service during the study or within 12 months of administration of the malaria inoculum.
7. The volunteer has a diagnosis of schizophrenia, bi-polar disease, severe depression or other severe (disabling) chronic psychiatric disorder. Participants who are receiving a single anti-depressant 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.
8. Has been hospitalised in the past 5 years prior to enrolment for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
9. Known pre-existing prolongation of the QTc interval. Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical conditions known to prolong the QTc interval eg volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
10. Recent or current therapy with antibiotic or drug with potential antimalarial activity (tetracycline, azithromycin, clindamycin, hydroxychloroquine etc).
11. Known allergy to any medicine containing doxycycline, other tetracyclines, or any other ingredients contained within the medicine.
12. Recent or current therapy with medicine containing vitamin A or retinoids such as isotretinoin (eg Absorica, Accutane, Amnesteem, Claravis, Sotret) and etretinate (eg Tegison).
13. Concomitant use of any drug which is metabolized by the cytochrome enzyme CYP2D6 (eg 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 non-sedating antihistamines (terfenadine, astemizole), cisapride.
14. 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 axis suppression such as 1mg/kg/day or prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 micrograms per day or fluticasone 750 micrograms).
15. Presence of acute infectious disease or fever (e.g. sub-lingual temperature greater than or equal to 38.5oC) within the five days prior to the study product administration.
16. Evidence of acute illness within the 4 weeks before trial prior to screening and enrollment.
17. Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic or autoimmune disease by history, physical examination and/or laboratory studies including urinalysis.
18. Alcohol consumption greater than community norms (ie more than 21 standard drinks per week for males).
19. A history of drug habituation, or any prior intravenous usage of an illicit substance.
20. Medical requirement for intravenous administration of immunoglobulin or blood transfusions.
21. Participation in any investigational product study within 8 weeks preceding the study.
22. Participation in any research study involving significant blood sampling, or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding the study.
23. Have ever received a blood transfusion.
24. Positive test for HIV, Hepatitis B, Hepatitis C, Human T-cell Lymphotropic Virus I and II(HTLV I and II), TB or syphilis.
25. Any clinically significant biochemical or haematologic abnormality (Hb must be greater than or equal to 13.5g/dL).
26. Ingestion of any poppy seeds within the 48 hours prior to the screening blood test (volunteers will be advised by phone not to consume any poppy seeds in this time period).
27. Detection of the following drugs: amphetamines, methamphetamines, barbituates, benzodiazepines, cocaine, methadone, opiates, phencyclidine, tetrahydrocannabinols or tricyclic antidepressants, in the urine drug screen unless there is an explanation acceptable to the medical investigator (eg the subject has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and/or the subject has a negative drug screen on retest by the pathology laboratory.
28. Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants
29. History of malaria
30. Travelled to or lived ( greater than 2 weeks) in a malaria-endemic country during the past 12 months or planned to travel to a malaria-endemic country during the course of the study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This study is uncontrolled as the same treatment is applied to all subjects in the group.
Phase
Phase 0
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
not applicable

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/01/2016
Actual
Date of last participant enrolment
Anticipated
20/01/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
3
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 292222 0
Government body
Name [1] 292222 0
NHMRC
Country [1] 292222 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
c/- Chris Davis
Griffith University, Gold Coast Campus
Institute for Glycomics, Building G26
Parklands Drive, Southport
Queensland
4215
Country
Australia
Secondary sponsor category [1] 290899 0
None
Name [1] 290899 0
Not applicable
Address [1] 290899 0
Not applicable
Country [1] 290899 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 293696 0
Griffith University Human Research Ethics Committee
Ethics committee address [1] 293696 0
Griffith University, Gold Coast Campus
Rm 360, Science Engineering and Architecture (G39)
Parklands Drive
Southport, QLD 4215
Ethics committee country [1] 293696 0
Australia
Date submitted for ethics approval [1] 293696 0
14/10/2015
Approval date [1] 293696 0
Ethics approval number [1] 293696 0

Summary
Brief summary
This study involves examining the persistence and immunogenicity of P. falciparum 7G8 blood stage parasites following commencement of anti-malarial treatment with doxycycline. Participants will receive a single inoculum of purified malaria parasites followed one hour later by commencement of doxycycline treatment. Following this, we will measure the level of parasites in the blood-stream of the participants. We will also be assessing the way the immune system responds to the inoculum and the safety and tolerability of the inoculum. Characterising the persistence, immunogenicity, safety and tolerability of the malaria parasite following commencement of doxycycline treatment is important as this data may contribute to the development of novel malaria vaccine strategies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60982 0
Prof Michael Good
Address 60982 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60982 0
Australia
Phone 60982 0
61755529435
Fax 60982 0
61755528098
Email 60982 0
[email protected]
Contact person for public queries
Name 60983 0
Dr Danielle Stanisic
Address 60983 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60983 0
Australia
Phone 60983 0
61755528051
Fax 60983 0
61755528098
Email 60983 0
[email protected]
Contact person for scientific queries
Name 60984 0
Dr Danielle Stanisic
Address 60984 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60984 0
Australia
Phone 60984 0
61755528051
Fax 60984 0
61755528098
Email 60984 0
[email protected]

No information has been provided regarding IPD availability


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
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