Developing a Controlled Human Infection Model for Group B Streptococcus (CHIM_GBS)

NCT04059510 | Unknown

• 1 other identifier: 2019.0062
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis. In 2015, it was estimated that worldwide there were at least 320,000 infants with invasive GBS disease, 90,000 infant deaths and 10,000 cases of children with disability related to GBS meningitis. Maternal rectovaginal colonization with GBS is the biggest risk factor for neonatal GBS sepsis and meningitis within the first 6 days of life, with transmission of the bacteria from mother to baby occurring around the time of birth. An estimated 20-35% of pregnant women are colonised with GBS. 1-2% of neonates born to GBS-colonised women develop invasive GBS disease in the absence of intrapartum antibiotic prophylaxis (IAP). The current strategy to prevent neonatal GBS is to give antibiotics during labour, called IAP. This has various limitations and is not easily achieved outside of high income settings. Additionally, widespread antibiotic use raises concerns about antibiotic resistance. A better approach would be a vaccine for GBS however in order to test any vaccines it would be necessary to develop a controlled human infection model whereby healthy female volunteers are artificially colonised with GBS to test the vaccines efficacy. Before developing these human infection models researchers need to better understand how women become colonised with GBS and whether antibodies in the blood and at the mucosal surfaces provide protection. This study will be observational and will test the antibody levels at the vaginal mucosa and in the blood of a group of women who are naturally colonised with GBS at the start of the study and a group who are not colonised. Investigators will follow women up over 12 weeks to observe how colonisation changes and the effect that this has on the mucosal and blood stream antibody concentrations. This will inform the development of human infection studies.

Conditions

Group B Streptococcus

Keywords

Streptococcus agalactiae; GBS

Outcome Measures

Primary Outcomes (1)

• The concentration of serotype-specific IgG in vaginal secretions at baseline and at two weekly intervals

  Serotype specific IgG in vaginal secretions at baseline and at two weekly time intervals will be analysed by geometric mean and median titres calculated and comparisons made by t-test or non-parametric test as appropriate. Significance is set at the 5% level.

  12 weeks

Secondary Outcomes (5)

• If the concentration of GBS IgG antibody in blood and mucosa affects the likelihood of colonisation with GBS

  12 weeks

• If we can predict colonisation from GBS IgG antibody concentration in blood and at the mucosa

  12 weeks

• Evaluating how many women become colonised over a three month period who were uncolonised at baseline

  12 weeks

• Evaluating how many women become uncolonised over a three month period who were colonised at baseline

  12 weeks

• Acceptability of sampling methods

  12 months

Study Arms (3)

Screening for GBS

Women will be recruited for screening for GBS in the UK and Uganda (250 at each site). At screening women will be consented for a vaginal and rectal swab to assess for GBS carriage and will also undergo an asymptomatic STI screen according to local usual practice. Anyone who meets the full inclusion criteria following screening will be invited to take part in the sampling study until the recruitment targets are reached. If any woman tests positive for any of the infections, she will be referred to a local centre for treatment and may still be included after completed treatment for the infection.

Procedure: rectovaginal swab; Procedure: pregnancy test; Procedure: Blood test

Sampling method optimisation

If a woman is deemed to meet all inclusion criteria and no exclusion criteria following screening and is willing to take part in the sampling method optimisation study, she will be consented again for the further study including consent (optional) for participation in a focus group at the end of the study. 100 eligible women will be recruited on to this part of the study (50 colonised with GBS at baseline and 50 uncolonised with GBS at baseline) at each site (UK and Uganda). The sampling study will last for 12 weeks and samples collected include: * A self-taken low vaginal swab * A self-taken rectal swab * Menstrual cup fluid * Serum sample * Urine pregnancy tests

Procedure: rectovaginal swab; Procedure: pregnancy test; Procedure: Menstrual cup; Procedure: Blood test

Focus groups

In the UK investigators will recruit up to 20 women from the sampling study to take part in focus groups about their experiences with self-sampling methods and the acceptability of controlled human infection models. Consent to participate in focus group discussions will be included as part of the consent to take part in the sampling study but will be optional. Women may opt out of the focus groups at any time but remain in the sampling study if they choose. In Uganda, the investigator will recruit more widely to our focus groups, including representation from midwives and the participant's partners and community leaders.The investigator will explore potential issues around maternal vaccination, and traditional and contemporary views on taking vaginal swabs and blood samples.

Other: Focus group

Interventions

rectovaginal swab PROCEDURE

Self taken rectal and vaginal swab

Also known as: rectal and vaginal swab

Sampling method optimisation; Screening for GBS

pregnancy test PROCEDURE

Urine pregnancy test

Also known as: hcg urine test, urine pregnancy test

Sampling method optimisation; Screening for GBS

Menstrual cup PROCEDURE

Menstrual cup vaginal fluid collection

Also known as: feminine hygiene product

Sampling method optimisation

Blood test PROCEDURE

Venous blood sample

Sampling method optimisation; Screening for GBS

Focus group OTHER

Focus group responses will be audio-recorded, transcribed, and analysed by developing a coding framework and identifying emerging themes

Focus groups

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Non-pregnant women age 18-40
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers will be recruited from the local population using a variety of methods including face to face invitation (e.g. at research events or freshers fairs), posters, adverts on radio and or social media, emails to participants who have registered on our volunteers database, adverts on websites and flyers.

You may qualify if:

• Age 18-40
• Healthy
• Willing to comply with study protocol requirements
• Able to give informed consent
• Willing not to become pregnant and use adequate contraception for length of study

You may not qualify if:

• Latex allergy
• Intra-Uterine Device/Intra-Uterine System
• Presence of untreated sexually transmitted infections at baseline
• Known Diabetes
• Genital dermatoses
• Diagnosis of Cervical Intraepithelial Neoplasia within past 3 years
• Current pregnancy
• Post-Menopausal

Sponsors & Collaborators

• St George's, University of London: lead

Study Sites (1)

St George's, University of London

London, SW17 0RE, United Kingdom

RECRUITING

Related Publications (7)

• Seale AC, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, Madrid L, Blencowe H, Cousens S, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Ip M, Le Doare K, Madhi SA, Rubens CE, Saha SK, Schrag SJ, Sobanjo-Ter Meulen A, Vekemans J, Lawn JE. Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children. Clin Infect Dis. 2017 Nov 6;65(suppl_2):S200-S219. doi: 10.1093/cid/cix664.

  PMID: 29117332 BACKGROUND

• Le Doare K, Heath PT, Plumb J, Owen NA, Brocklehurst P, Chappell LC. Uncertainties in Screening and Prevention of Group B Streptococcus Disease. Clin Infect Dis. 2019 Aug 1;69(4):720-725. doi: 10.1093/cid/ciy1069.

  PMID: 30561556 BACKGROUND

• Le Doare K, Kampmann B, Vekemans J, Heath PT, Goldblatt D, Nahm MH, Baker C, Edwards MS, Kwatra G, Andrews N, Madhi SA, Ter Meulen AS, Anderson AS, Corsaro B, Fischer P, Gorringe A. Serocorrelates of protection against infant group B streptococcus disease. Lancet Infect Dis. 2019 May;19(5):e162-e171. doi: 10.1016/S1473-3099(18)30659-5. Epub 2019 Jan 22.

  PMID: 30683467 BACKGROUND

• Le Doare K, Faal A, Jaiteh M, Sarfo F, Taylor S, Warburton F, Humphries H, Birt J, Jarju S, Darboe S, Clarke E, Antonio M, Foster-Nyarko E, Heath PT, Gorringe A, Kampmann B. Association between functional antibody against Group B Streptococcus and maternal and infant colonization in a Gambian cohort. Vaccine. 2017 May 19;35(22):2970-2978. doi: 10.1016/j.vaccine.2017.04.013. Epub 2017 Apr 24.

  PMID: 28449969 BACKGROUND

• Russell NJ, Seale AC, O'Driscoll M, O'Sullivan C, Bianchi-Jassir F, Gonzalez-Guarin J, Lawn JE, Baker CJ, Bartlett L, Cutland C, Gravett MG, Heath PT, Le Doare K, Madhi SA, Rubens CE, Schrag S, Sobanjo-Ter Meulen A, Vekemans J, Saha SK, Ip M; GBS Maternal Colonization Investigator Group. Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses. Clin Infect Dis. 2017 Nov 6;65(suppl_2):S100-S111. doi: 10.1093/cid/cix658.

  PMID: 29117327 BACKGROUND

• Le Doare K, O'Driscoll M, Turner K, Seedat F, Russell NJ, Seale AC, Heath PT, Lawn JE, Baker CJ, Bartlett L, Cutland C, Gravett MG, Ip M, Madhi SA, Rubens CE, Saha SK, Schrag S, Sobanjo-Ter Meulen A, Vekemans J, Kampmann B; GBS Intrapartum Antibiotic Investigator Group. Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review. Clin Infect Dis. 2017 Nov 6;65(suppl_2):S143-S151. doi: 10.1093/cid/cix654.

  PMID: 29117324 BACKGROUND

• Haeusler IL, Daniel O, Isitt C, Watts R, Cantrell L, Feng S, Cochet M, Salloum M, Ikram S, Hayter E, Lim S, Hall T, Athaide S, Cosgrove CA, Tregoning JS, Le Doare K. Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable. Clin Exp Immunol. 2022 Aug 19;209(2):188-200. doi: 10.1093/cei/uxac066.

  PMID: 35802786 DERIVED

MeSH Terms

Interventions

Administration, Rectal; Pregnancy Tests; Menstrual Hygiene Products; Feminine Hygiene Products; Hematologic Tests; Focus Groups

Intervention Hierarchy (Ancestors)

Administration, Mucosal; Administration, Topical; Drug Administration Routes; Drug Therapy; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Obstetrical and Gynecological; Investigative Techniques; Equipment and Supplies; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Catherine Cosgrove, PhD,MRCP

  St Georges University Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Isitt, MBChB, MRC

CONTACT

+ 44 (0) 208 725 2316; cisitt@sgul.ac.uk

Lola Oladipo

CONTACT

+44 (0)208 725 5382; loladipo@sgul.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 16, 2019
• Study Start: November 4, 2019
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: February 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)