nderstanding how the immune system responds to repeated malaria infections
- Conditions
- P. falciparum malariaInfections and Infestations
- Registration Number
- ISRCTN85988131
- Lead Sponsor
- niversity of Oxford
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 22
Participant inclusion criteria as of 30/04/2024:
1. Healthy, malaria-naïve adult aged 18 to 45 years old
2. Able and willing (in the Investigator’s opinion) to comply with all study requirements
3. Willing to allow the Investigators to access the volunteer’s electronic medical records or discuss the volunteer’s medical history with their GP
4. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study
5. Able and willing to provide written informed consent to participate in the trial
6. Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels
7. Agreement to permanently refrain from blood donation during and after the study, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines
8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of anti-malarial treatment
9. Willing to take a curative anti-malarial treatment regimen following CHMI
10. Able to answer all questions on the informed consent questionnaire correctly at the first or second attempt
11. Able to travel to CCVTM
12. Willingness to be registered on the TOPS database (The Overvolunteering Prevention System; www.tops.org.uk).
Previous participant inclusion criteria:
1. Healthy, malaria-naïve, CMV-seropositive adult aged 18 to 45 years old
2. Able and willing (in the Investigator’s opinion) to comply with all study requirements
3. Willing to allow the Investigators to access the volunteer’s electronic medical records or discuss the volunteer’s medical history with their GP
4. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study
5. Able and willing to provide written informed consent to participate in the trial
6. Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels
7. Agreement to permanently refrain from blood donation during and after the study, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines
8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of anti-malarial treatment
9. Willing to take a curative anti-malarial treatment regimen following CHMI
10. Able to answer all questions on the informed consent questionnaire correctly at the first or second attempt
11. Able to travel to CCVTM
12. Willingness to be registered on the TOPS database (The Overvolunteering Prevention System; www.tops.org.uk).
Participant exclusion criteria as of 30/04/2024:
1. Red blood cells negative for the Duffy antigen/chemokine receptor (DARC) (this exclusion criterion is for Group 2 only)
2. Body weight < 50 kg or Body Mass Index (BMI) < 18.0 at screening
3. History of clinical malaria (any species) or previous participation in any malaria vaccine trial or CHMI
4. History of yellow fever virus infection or prior receipt of YFV
5. Travel to a clearly malaria endemic locality during the study period or within the preceding six months
6. Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three months
7. Receipt of any vaccine (except the COVID-19 vaccine or flu) in the 30 days preceding enrolment, or planned receipt during the study period
8. Receipt of a COVID-19 or flu vaccine within 2 weeks before the day of CHMI or planned receipt of a COVID-19 or flu vaccine prior to expected completion of anti-malarial treatment (around 2 to 3 weeks after day of challenge based on experience in previous P. falciparum CHMI studies to date)
9. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
10. Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period
11. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
12. Previous thymectomy or known or suspected thymic disorder
13. Hypersensitivity reactions to eggs, chicken proteins or any component of Stamaril
14. Any history of anaphylaxis in reaction to vaccinations
15. Any confirmed or suspected bleeding disorders
16. Current use of anticoagulant medication e.g. low molecular weight heparin, warfarin, apixaban, edoxaban
17. Known allergy to local anaesthetics e.g. lidocaine
18. Use of systemic antibiotics with known anti-malarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
19. Use of anti-malarials within 30 days of CHMI
20. Any clinical condition known to prolong the QT interval
21. History of cardiac arrhythmia, including clinically relevant bradycardia
22. Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
23. Family history of congenital QT prolongation or sudden death
24. An estimated ten-year risk of fatal cardiovascular disease of > = 5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE) shown in Appendix B in the protocol
25. Use of medications known to have a potentially clinically significant interaction with Riamet
26. Any other contraindications/known hypersensitivities to Riamet or Malarone
27. History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait, G6PD deficiency or any haematological condition that could affect susceptibility to malaria infection
28. Pregnancy, lactation or intention to become pregnant during the study
29. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
30. History of serious psychiatric condition that may affect participation in the study
31. Any other serious chronic illness requiring hospital specialist supervision
32. Suspected or known current alcohol misuse as defined b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Parasite growth rate measured using plasmodium falciparum-specific 18S rRNA qPCR assay and linear modelling for parasite multiplication rate (PMR)<br>2. Proliferation rate and half-life of total and Yellow fever vaccine (YFV)-specific memory T cells measured using flow cytometry with cell sorting and mass spectrometry analysis of deuterium incorporation<br><br>
- Secondary Outcome Measures
Name Time Method