Condition category
Infections and Infestations
Date applied
12/03/2019
Date assigned
01/05/2019
Last edited
14/08/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Public

Primary contact

Dr Emily Webb

ORCID ID

Contact details

LSHTM
Keppel St
London
WC1E 7HT
United Kingdom
+44 (0)207 9272012
emily.webb@lshtm.ac.uk

Type

Scientific

Additional contact

Prof Alison Elliott

ORCID ID

Contact details

MRC/UVRI and LSHTM Uganda Research Unit
Entebbe
UVRI P.O.Box 49
Uganda
+44 (0)207 6368636
alison.elliott@mrcuganda.org

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

v1

Study information

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

Acronym

POPVAC trial A

Study hypothesis

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

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

Study design

Single-centre open individually randomised two parallel group trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Schools

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

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 names

Praziquantel

Primary outcome measure

1. BCG: BCG-specific IFN-gamma ELIspot response 8 weeks post BCG immunisation
2. YF-17D: neutralising antibody titres (plaque-reduction neutralisation test) at 4 weeks post YF immunisation
3. Ty21a: Salmonella typhi lipopolysaccharide (LPS)-specific immunoglobulin(Ig)G concentration at 4 weeks post Ty21a immunisation
4. HPV: IgG specific for L1-proteins of HPV-16/18 at 4 weeks post HPV priming immunisation
5. Td: tetanus and diphtheria toxoid-specific IgG concentration at 4 weeks post Td immunisation

Secondary outcome measures

Current secondary outcome measures as of 24/07/2019:
1. Protective immunity. Proportions with protective neutralising antibody (YF); protective IgG levels (TT); seroconversion rates (Ty21a) at 4 weeks post the corresponding immunisation
2. Response waning. Primary outcome measures (all vaccines) repeated at week 52, and area-under-the curve (AUC) analyses
3. Priming versus boosting. Effects on priming versus boosting will be examined for HPV only, comparing outcomes 4 weeks after the first, and 4 weeks after the second vaccine dose
4. Current S. mansoni infection status and intensity. This will be determined by serum/plasma levels of circulating anodic antigen (CAA). The method is quantitative, highly specific for Schistosoma infection, and much more sensitive than the conventional Kato Katz method. CAA will be assessed retrospectively on stored samples collected at baseline, on immunisation days, and on primary and secondary endpoint days.

Previous secondary outcome measures:
1. Protective immunity. Proportions with protective neutralising antibody (YF); protective IgG levels (TT); seroconversion rates (Ty21a) at 4 weeks post the corresponding immunisation
2. Response waning. Primary outcome measures (all vaccines) repeated at week 52, and area-under-the curve (AUC) analyses
3. Priming versus boosting. Effects on priming versus boosting will be examined for HPV only, comparing outcomes 4 weeks after the first, and 4 weeks after the second vaccine dose

Overall trial start date

01/05/2018

Overall trial end date

31/08/2020

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Healthy volunteer

Age group

Child

Gender

Both

Target number of participants

480

Participant 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

Recruitment start date

08/07/2019

Recruitment end date

23/08/2019

Locations

Countries of recruitment

Uganda

Trial participating centre

MRC/UVRI and LSHTM Uganda Research Unit
Plot 51-59 Nakiwogo Road
Entebbe
-
Uganda

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine

Sponsor details

Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)207 636 8636
postmaster@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The researchers plan to publish the study protocol on around 01/12/2019. They will also add the statistical analysis plan to the trial registration before database lock. They then plan to publish the results of the trial in a high-impact peer-reviewed journal with an intention to publish date of 31/08/2021.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/08/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.