The effect of intensive treatment for schistosomiasis on response to vaccines among island adolescents in Uganda
| ISRCTN | ISRCTN60517191 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60517191 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | v1 |
| Sponsor | London School of Hygiene and Tropical Medicine |
| Funder | Medical Research Council |
- Submission date
- 12/03/2019
- Registration date
- 01/05/2019
- Last edited
- 21/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Infectious diseases remain very common in low-income countries (LICs). Vaccines protect people against infectious diseases, but several important vaccines do not work as well in LICs compared to high-income countries (HICs) and in rural, compared to urban, settings. One possible reason for this might be that people living in these settings are more likely to have worm infections. Worm infections impact on the immune system and may change an infected person’s response to a vaccine. This study aims to investigate whether treating adolescents infected with schistosomiasis, a parasitic worm infection, before vaccination, will lead to a better immune response to these vaccines.
Who can participate?
Healthy volunteer children (aged 9-17, with no gender restriction) from selected schools located in the Koome islands of Lake Victoria, Uganda. Schistosomiasis is very common in this area.
What does the study involve?
Children are randomly allocated to receive either intensive or standard praziquantel treatment for schistosomiasis. Intensive praziquantel treatment is three doses, 2 weeks apart, of praziquantel before vaccination followed by quarterly praziquantel for a period of one year. Standard praziquantel treatment is once a year. They are then vaccinated against tuberculosis, yellow fever, human papilloma virus (which can cause cancer of the cervix [or opening] of the womb, and other cancers), typhoid and tetanus. Four weeks after vaccination, their immune responses to each vaccine are measured.
What are the possible benefits and risks of participating?
Participants will benefit from receiving the vaccines and treatments as they are expected to provide protection against infectious diseases. Participants and their families, schools and communities will benefit from improved understanding of schistosomiasis and vaccines. No major risks to the participants are anticipated since all the treatments and vaccines to be given are licensed and known to be safe. The main risk to participants will be time lost from school work, and the researchers will work with teachers and parents to minimise this. Very rarely, a vaccine may cause a severe allergic reaction, so individuals who have previously suffered a possible allergic reaction to drugs or vaccines or their components will not be included in the study.
Where is the study run from?
The host institution for the study will be the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit (MRC/UVRI & LSHTM), Entebbe, Uganda.
When is the study starting and how long is it expected to run for?
May 2018 to August 2020
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Prof. Alison Elliott
alison.elliott@lshtm.ac.uk
Contact information
Public
LSHTM
Keppel St
London
WC1E 7HT
United Kingdom
| Phone | +44 (0)207 9272012 |
|---|---|
| emily.webb@lshtm.ac.uk |
Scientific
MRC/UVRI and LSHTM Uganda Research Unit
Entebbe
UVRI P.O.Box 49
Uganda
| Phone | +44 (0)207 6368636 |
|---|---|
| alison.elliott@mrcuganda.org |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre open individually randomised two parallel group trial |
| Secondary study design | Randomised parallel trial |
| Participant information sheet | ISRCTN60517191_PIS_05Sept2020.pdf |
| Scientific title | Population differences in vaccine response: the role, reversibility and mediators of immunomodulation by chronic infections in the tropics (POPVAC). Trial Protocol A: the effect of intensive treatment for schistosomiasis on response to vaccines among island adolescents in Uganda |
| Study acronym | POPVAC trial A |
| Study objectives | Schistosoma mansoni infection suppresses responses to unrelated vaccines, and this effect can be reversed, at least in part, by intensive praziquantel treatment intervention. |
| Ethics approval(s) | 1. Approved 05/09/2018, MRC/UVRI and LSHTM Uganda Research Unit Research Ethics Committee (Plot 51-59, Nakiwogo Road, Entebbe, P.O. Box 49, Entebbe-Uganda; +256 414 320 385/6; directoruvri@uvri.go.ug), ref: GC/127/18/09/680 2. Approved 07/05/2019, Uganda National Council for Science and Technology (Plot 6, Kimera Road, Ntinda, P.O. Box 6884, Kampala-Uganda; +256 414 705500; infor@uncst.go.ug), ref: HS 2486 3. Approved 28/05/2019, National Drug Authority (Plot 19 Lumumba Avenue, P.O. Box 23096, Kampala, Uganda; +256 417 788 100; ndaug@nda.or.ug), ref: 351/NDA/DPS/05/2019 4. Approved 05/06/2019, London School of Hygiene and Tropical Medicine Interventional Ethics Committee (Keppel Street, London WC1E 7HT; +44(0)20 7636 8636; ethics@lshtm.ac.uk), ref: 16032 |
| Health condition(s) or problem(s) studied | Vaccine responses |
| Intervention | A randomisation code will be generated by the trial statistician using a randomly permuted block size. Participants will be allocated in a 1:1 ratio to receive either intensive or standard praziquantel treatment. Participants in the intensive arm will receive three doses of praziquantel (PZQ) (40mg/kg, assessed by height pole) each two weeks apart (the last of these 2-4 weeks before immunisation), followed by quarterly PZQ (approximately; timings adjusted to accommodate school terms) during follow up. Participants in the standard arm will receive annual PZQ (Uganda Ministry of Health (MoH) policy) given after immunisation and after primary endpoint sampling. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Praziquantel |
| Primary outcome measure(s) |
1. BCG: BCG-specific IFN-gamma ELIspot response 8 weeks post BCG immunisation |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 24/07/2019: |
| Completion date | 30/11/2020 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 9 Years |
| Upper age limit | 17 Years |
| Sex | All |
| Target sample size at registration | 480 |
| Total final enrolment | 479 |
| Key inclusion criteria | 1. Attending the selected school and planning to continue to attend the school for the duration of the study 2. Aged 9 to 17 year and enrolled in primary 4, 5 or 6 3. Written informed consent by parent or guardian 4. Written informed assent by participant 5. Agree to avoid pregnancy for the duration of the trial (female only) 6. Willing to provide locator information and to be contacted during the course of the trial 7. Able and willing (in the investigator's opinion) to comply with all the study requirements |
| Key exclusion criteria | 1. Clinically significant history of immunodeficiency (including HIV), cancer, cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness 2. History of serious psychiatric condition or disorder 3. Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents within 2 months prior to enrolment 4. History of allergic reaction to immunisation or any allergy likely to be exacerbated by any component of the study vaccines including egg or chicken proteins 5. History of previous immunisation with YF, oral typhoid or HPV vaccine; previous immunisation with BCG or Td at age >5 years 6. Tendency to develop keloid scars 7. Haemoglobin less than 82g/L 8. Positive HIV serology 9. Positive pregnancy test 10. Female currently lactating, confirmed pregnancy or intention to become pregnant during the trial period 11. Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccines for 30 days prior to dosing with the study vaccine, or planned use during the study period 12. Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial immunisation date |
| Date of first enrolment | 08/07/2019 |
| Date of final enrolment | 23/08/2019 |
Locations
Countries of recruitment
- Uganda
Study participating centre
Entebbe
-
Uganda
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in repository |
| IPD sharing plan | The de-identified individual participant data that underlie the results reported in journal articles will be stored in a non-publically available repository (LSHTM Data Compass), together with a data dictionary. This will be done at the time of publication. Each dataset will be allocated a unique digital object identifier (DOI). Researchers who would like to access the data may submit a request through LSHTM Data Compass, detailing the data requested, the intended use for the data, and evidence of relevant experience and other information to support the request. The request will be reviewed by the Principal Investigator in consultation with the POPVAC Steering Committee, with oversight from the UVRI and LSHTM ethics committees. In line with the MRC policy on Data Sharing, there will have to be a good reason for turning down a request. Patient Information Sheets and consent forms specifically referenced making anonymised data available and this has been approved by the relevant ethics committees. Researchers given access to the data will sign data sharing agreements which will restrict the use to answering pre-specified research questions. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/11/2024 | 21/10/2024 | Yes | No | |
| Protocol article | 16/02/2021 | 05/05/2022 | Yes | No | |
| Protocol article | scientific rationale and cross-cutting analyses | 16/02/2021 | 26/10/2022 | Yes | No |
| Participant information sheet | Information sheet for participants 9 to 12 years old | 05/09/2020 | 09/07/2024 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Statistical Analysis Plan | 01/11/2019 | 19/03/2020 | No | No | |
| Statistical Analysis Plan | version v2.0 | 01/12/2020 | 27/01/2021 | No | No |
Additional files
- ISRCTN60517191_SAP_01Nov19.doc
- Uploaded 19/03/2020
- ISRCTN60517191_SAP_v2.0_01Dec2020.doc
- uploaded 27/01/2021
- ISRCTN60517191_PIS_05Sept2020.pdf
- Information sheet for participants 9 to 12 years old
Editorial Notes
21/10/2024: Publication reference added.
09/07/2024: Participant information sheet added.
05/06/2024: The intention to publish date was changed from 31/12/2023 to 01/07/2024.
10/03/2023: The intention to publish date was changed from 31/03/2023 to 31/12/2023.
26/10/2022: Publication reference added.
05/05/2022: The following changes have been made:
1. Publication reference added.
2. The publication and dissemination plan has been updated.
3. The intention to publish date has been changed from 30/11/2021 to 31/03/2023.
27/01/2021: The statistical analysis plan version 2 was uploaded as an additional file.
11/09/2020: Internal review.
05/08/2020: The following changes have been made:
1. The overall trial end date has been changed from 31/08/2020 to 30/11/2020.
2. The intention to publish date has been changed from 31/08/2021 to 30/11/2021.
3. The final enrolment number has been added.
10/06/2020: The following changes were made to the trial record:
1. The publication and dissemination plan was updated and the IPD sharing statement was added.
2. The participant-level data was changed from "To be made available at a later date" to "Stored in repository".
19/03/2020: Uploaded statistical analysis plan.
14/08/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 17/06/2019 to 08/07/2019.
2. The recruitment end date was changed from 19/07/2019 to 23/08/2019.
3. The overall trial end date was changed from 30/04/2022 to 31/08/2020.
4. The intention to publish date was changed from 30/04/2023 to 31/8/2021.
24/07/2019: The following changes were made to the trial record:
1. The ethics approval was added.
2. The secondary outcome measures were changed.
27/03/2019: Trial's existence confirmed by MRC/UVRI REC.
