Immunity to liver-stage Plasmodium falciparum malaria parasites
| ISRCTN | ISRCTN61332343 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN61332343 |
| Secondary identifying numbers | NL72410.091.19 |
- Submission date
- 27/10/2022
- Registration date
- 07/11/2022
- Last edited
- 10/06/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Malaria is a major cause of death in endemic regions of the world. The malaria parasite Plasmodium falciparum has an initial asymptomatic (without symptoms) life stage within the human host (liver stage). Further development of the parasite at the liver stage would prevent progression into the pathogenic (disease-causing) blood stage. As a result, the liver stage is a target for many current malaria vaccine candidates, but immunity against this stage is not well understood. This study aims to provide further insights into immunity to liver-stage Plasmodium falciparum.
Who can participate?
Patients aged over 18 years undergoing medically-indicated partial liver resection (surgery to remove part of the liver) for underlying disease
What does the study involve?
1. 6 ml blood will be drawn for HLA-A2 phenotyping
2. 24 ml blood will be drawn before liver surgery through an existing line
3. Liver tissue will be obtained that is not required for diagnostic purposes and would otherwise be considered medical waste, which will be processed to obtain hepatocytes (liver cells) and liver-resident immune cells
What are the possible benefits and risks of participating?
There is no direct benefit to study participation. The risks associated with blood samples are minor and there is no additional risk to patients associated with the processing of already-removed liver tissue.
Where is the study run from?
Radboud University Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
December 2019 to June 2026
Who is funding the study?
Radboud University Medical Center (Netherlands)
Who is the main contact?
Dr Matthew B.B. McCall, matthew.mccall@radboudumc.nl
Contact information
Principal Investigator
PO Box 9101
Nijmegen
6500 HB
Netherlands
 ORCID ID |
0000-0002-2473-0943 |
|---|---|
| Phone | +31 (0)243619515 |
| matthew.mccall@radboudumc.nl |
Study information
| Study design | Single-centre investigator-initiated exploratory study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Immunological study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | 42677_PIS_V3_27Mar20.pdf |
| Scientific title | Immunity to liver-stage Plasmodium falciparum in peripheral and tissue-resident immune cells |
| Study acronym | LYTIC |
| Study objectives | In this study the researchers will establish an in vitro assay using leukocytes (CD8+ T cell line, fresh peripheral blood mononuclear cells [PBMCs] and liver-resident lymphocytes) in combination with freshly isolated human hepatocytes to study respectively cytolytic T cell and innate immune recognition and killing of P. falciparum-infected hepatocytes |
| Ethics approval(s) | Approved 18/05/2020, METC Oost-Nederland (Postbus 9101, 6500 HB Nijmegen, Netherlands; +31 (0)24 361 31 54; metcoost-en-cmo@radboudumc.nl), ref: 2019-6064 |
| Health condition(s) or problem(s) studied | Antimalarial immune response to liver-stage P. falciparum |
| Intervention | An observational study applying HLA-A2 phenotyping; isolation of hepatocytes and intrahepatic immune cells; expansion of a circumsporozoite protein (CSP)-specific CD8+ T cell line; antimalarial immune response to liver-stage P. falciparum 1. 6 ml blood will be drawn by venepuncture upon receipt of informed consent for HLA-A2 phenotyping 2. 24 ml blood will be drawn prior to liver surgery via an existing intravenous or arterial line 3. Liver tissue will be obtained from the recruited patients undergoing medically-indicated partial liver resection for underlying disease, that is not required for diagnostic purposes and would otherwise be considered medical waste, and processed to obtain hepatocytes and liver-resident immune cells |
| Intervention type | Other |
| Primary outcome measure | Measured at the surgery visit: 1. Recognition of P. falciparum-infected hepatocytes by CSP-specific cytolytic CD8+ T cells and hepatic and peripheral innate/innate-like lymphocytes measured using flow cytometry 2. Killing of P. falciparum-infected hepatocytes by CSP-specific cytolytic CD8+ T cells and hepatic and peripheral innate/innate-like lymphocytes measured using fluorescence microscopy |
| Secondary outcome measures | Measured at the surgery visit: 1. Recognition and killing of P. falciparum-infected hepatocytes by CSP-specific cytolytic CD8+ T cell line measured using flow cytometry and fluorescence microscopy 2. Differences in recognition and killing of P. falciparum-infected hepatocytes between liver-resident and peripheral lymphocytes measured using flow cytometry and fluorescence microscopy 3. The individual lymphocyte (sub-)populations which contribute to the recognition and killing of P. falciparum-infected hepatocytes, identified using flow cytometry |
| Overall study start date | 23/12/2019 |
| Completion date | 30/06/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 45 |
| Key inclusion criteria | 1. Aged 18 years and above 2. Scheduled for partial liver resection for underlying disease 3. Signed written informed consent |
| Key exclusion criteria | 1. Known receipt of immunosuppressive or cytostatic agents within the past 3 months, except the use of topical and inhaled steroids 2. Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection, or other known clinically-relevant immunodeficient state |
| Date of first enrolment | 14/11/2022 |
| Date of final enrolment | 31/05/2026 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Geert Grooteplein Zuid 28
Nijmegen
6525 GA
Netherlands
Sponsor information
University/education
Department of Medical Microbiology
Geert Grooteplein Zuid 28
Nijmegen
6525 GA
Netherlands
| Phone | +31 (0)24 361 3663 |
|---|---|
| malariavaccin@radboudumc.nl | |
| Website | https://www.radboudumc.nl/en/research/departments/medical-microbiology |
"ROR" |
https://ror.org/05wg1m734 |
Funders
Funder type
University/education
Private sector organisation / Universities (academic only)
- Alternative name(s)
- Radboudumc, Radboud University Medical Center, Radboud University Nijmegen Medical Center, RUNMC
- Location
- Netherlands
Results and Publications
| Intention to publish date | 30/06/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | A final report will be prepared by the investigators at the Radboudumc and will be signed by the investigator. The investigator and sponsor will make every effort to publish the results in a peer-reviewed journal. |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be available upon request from the Principal Investigator (Matthew B.B. McCall, MD PhD; matthew.mccall@radboudumc.nl). Requests will be reviewed by a Data Access Committee and data sharing conditions agreed upon in a Data Use Agreement. Identifiable data will not be shared. The type of data that will be shared: anonymised immunological data that are generated in the study (identifiable data will not be shared) Timing for availability: data will be available after the publication of primary and secondary outcomes in a peer-reviewed journal (latest 1 year after the end of the study) Whether consent from participants was required and obtained: written consent from all study participants will be obtained; consent includes permission to use data for other purposes related to liver-stage immunity Comments on data anonymization: data will be pseudonymised: Study participants will be assigned a study identification code (LYTIC001, LYTIC002, etc). Study identification codes will be assigned by the study nurse in a chronological order where 001 will be assigned to the first study participant being enrolled and 002 to the second study participant. Study identification codes do not contain identifying elements. Study identification codes will be documented on the subject identification log which will be stored separately from all study documents containing identifiable data. Any ethical or legal restrictions: Export of data outside the EU may be subject to restrictions; human tissue samples shall be stored for a maximum of 15 years; study data shall be stored for a minimum of 20 years. Any additional comments: Data will be shared upon reasonable request, as assessed by the principal investigator and sponsor |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 3 | 27/03/2020 | 04/11/2022 | No | Yes |
| Protocol file | version 3.0 | 21/04/2020 | 04/11/2022 | No | No |
| Participant information sheet | version 4 | 07/11/2022 | 17/04/2023 | No | Yes |
| Protocol file | version 4 | 31/10/2022 | 17/04/2023 | No | No |
| Participant information sheet | version 6 | 07/06/2024 | 30/10/2024 | No | Yes |
| Protocol file | version 6 | 07/06/2024 | 30/10/2024 | No | No |
Additional files
Editorial Notes
10/06/2025: The intention to publish date was changed from 30/06/2025 to 30/06/2026.
06/06/2025: The following changes were made:
1. The recruitment end date was changed from 31/05/2025 to 31/05/2026.
2. The overall end date was changed from 30/06/2025 to 30/06/2026.
30/10/2024: Updated versions of the protocol and participant information sheet (PIS; in Dutch) were uploaded.
03/05/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 13/05/2024 to 31/05/2025.
2. The overall end date was changed from 31/12/2024 to 30/06/2025.
3. The intention to publish date was changed from 31/12/2024 to 30/06/2025.
4. The plain English summary was updated to reflect these changes.
17/04/2023: Updated versions of the protocol and participant information sheet (PIS; in Dutch) were uploaded.
01/12/2022: The sponsor details were updated.
04/11/2022: Trial's existence confirmed by the Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen.
