Transmission Reduction and Prevention With HPV Vaccination (TRAP-HPV) Study

This study is currently recruiting participants.
Verified March 2014 by McGill University
Sponsor:
Information provided by (Responsible Party):
Dr. Eduardo Franco, McGill University
ClinicalTrials.gov Identifier:
NCT01824537
First received: April 1, 2013
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

Human papillomavirus (HPV) is a member of the Papillomaviridae family of DNA viruses that is capable of infecting humans. HPV infection can cause cancers of the cervix, vulva, vagina, and anus in women or cancers of the anus and penis in men. Two prophylactic vaccines have been proven to be highly effective in preventing the acquisition of HPV infection and the genital precancerous lesions caused by it. However, we do not know yet if a previously infected individual, once vaccinated, would be less infective to her or his sexual partner. We plan to conduct a study, called Transmission Reduction And Prevention with HPV vaccination (TRAP-HPV) study to answer this question. It will include 500 sexually active couples (total of 1000 individuals) in university student health clinics in Montreal (age 18-26 years). It will be a randomized placebo-controlled, double-blinded intervention trial. Study participants will be followed up to 12 months. Behavioural and biological data will be collected at the time of study enrolment, then at months 2, 4, 6, 9 and 12 post-enrolment. The results of this trial will be invaluable in informing policies regarding vaccination of women and men.


Condition Intervention Phase
Human Papillomavirus Infection
Biological: HPV vaccine, Gardasil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Transmission Reduction and Prevention With HPV Vaccination (TRAP-HPV) Study: A Randomized Controlled Trial of the Efficacy of HPV Vaccination in Preventing Transmission of HPV Infection in Heterosexual Couples

Resource links provided by NLM:


Further study details as provided by McGill University:

Primary Outcome Measures:
  • The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (i.e., HPVs 6, 11, 16, and 18) in multiple anatomic sites in the placebo-treated sexual partners of persons who received Gardasil. [ Time Frame: At months 2, 4, 6, 9 and 12. ] [ Designated as safety issue: No ]
    Reduction in HPV type concordance (for the four target types) will be the main outcome evaluable as per the above group contrasts. These comparisons will be done with due attention to the enrolment virological status of the individuals. For instance, it is expected that a Havrix-treated woman who is positive for HPV 6 in the anal specimen but negative for this type in the vaginal specimen may derive benefit if her partner receives Gardasil, even if he is HPV-6 positive in the penile sample. The assumption is that protection via vaccination is pan-mucosal, via transudation of neutralizing antibodies; this protection may mediate transmission.


Estimated Enrollment: 1000
Study Start Date: September 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HPV vaccine
HPV vaccine intervention: The intervention vaccine will be Gardasil, a quadrivalent vaccine by Merck. This vaccine was chosen because it allows for the observation of 4 HPV outcomes (HPV 6, 11, 16, & 18) (the other available vaccine, Cervarix, protects against HPVs 16 and 18, only).
Biological: HPV vaccine, Gardasil
Once recruited, both individuals in a couple will be randomized independently to Gardasil or placebo (Havrix).
Placebo Comparator: Hepatitis A vaccine
The placebo comparator will be Havrix, by GSK. This control vaccine was chosen because hepatitis A immunization provides a similar health prevention incentive as HPV vaccination to study participants while preserving the scientific cogency of a "placebo" comparator. Gardasil requires administration of 3 doses, while Havrix only requires 2 doses. For this reason, a placebo injection (saline solution) will be added in between the Havrix vaccination regimen. Consequently, both treatment and control vaccines will have similar regimens, i.e., study entry, 2 months, and 6 months.
Biological: HPV vaccine, Gardasil
Once recruited, both individuals in a couple will be randomized independently to Gardasil or placebo (Havrix).

Detailed Description:

Two prophylactic vaccines (Gardasil by Merck, and Cervarix by GlaxoSmithKline) have been proven in randomized controlled trials (RCT) to be highly effective in preventing infection against the target HPV types (HPV-6/11/16/18, for Gardasil, and HPV-16/18, for Cervarix) and the cervical precancerous lesions caused by them. These vaccines have shifted the paradigm of prevention and are expected to have a major impact in reducing the burden of cervical cancer and of other HPV-associated malignancies, such as vulvar, vaginal, penile, anal, and oropharyngeal cancers, as well as benign HPV-associated conditions (in the case of Gardasil), such as anogenital warts and respiratory papillomatosis. However, little is known about the extent with which vaccination may reduce transmission between sexual partners; i.e. much remains to be understood on the effects of HPV vaccine in preventing transmission of target HPV types to sexual partners of vaccinated individuals and its impact on herd immunity.

The investigators propose to conduct a placebo-controlled, double-blinded RCT to measure the impact of vaccination in preventing HPV transmission within young (age 18-26) heterosexual couples at McGill and Concordia Universities in Montreal, Canada. Individual partners in 500 couples will be randomized to a treatment (Gardasil) or a control vaccine (Havrix, a hepatitis A vaccine). This control vaccine provides a similar health benefit incentive as HPV vaccination while preserving the scientific cogency of a "placebo" comparator. Risk factor data will be collected via computerized questionnaires at enrolment (time 0), 2, 4, 6, 9 and 12 months. At all time points, the investigators will measure HPV DNA infection status by PCR in both partners in exfoliated penile, anal, and oral samples from men and vaginal, anal, oral samples from women. Assessing pre-enrolment humoral immune response to HPV infection with a competitive Luminex immunoassay (CLIA) will be done in an enrolment blood sample from all study participants.

The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (types 6, 11, 16, and 18) in multiple anatomic sites in Havrix-treated sexual partners of participants who received Gardasil. The investigators hypothesize that HPV vaccination is effective in reducing the risk of HPV transmission to their sexual partners. They will use the Kaplan-Meier technique and logrank tests to compare the cumulative probability of HPV infection in sexual partners of vaccinated versus unvaccinated individuals against follow-up time, and Cox proportional hazards regression to estimate the effect of vaccination and other covariates on transmission of HPV to sexual partners. Statistical analyses will follow an intention-to-treat approach but additional regression models will examine the role of several candidate determinants in mediating transmission and the protective effects. Mixed-effects models will also be used to take advantage of the repeated measurements across visits, HPV types, and anatomical sites for the same subject.

In addition to the findings on protection to unvaccinated partners, it is expected that this study will provide valuable insights as to whether protection may exist for a vaccine recipient in preventing infection in an anatomical site in which a target type has not yet established infection. These findings will generate key parameter data to inform the extent of herd immunity in cost-effectiveness models of HPV vaccination. Such models are essential to arrive at rational science-driven policies of HPV vaccination in girls and boys in Canada.

(full protocol available upon request)

  Eligibility

Ages Eligible for Study:   18 Years to 26 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Couple must have been in a new relationship that started no more than three months prior to study entry
  • Both partners plan on remaining in Montreal for at least 1 year
  • Plan on having continued sexual contact with partner
  • Be willing to comply with study procedures

Exclusion Criteria:

  • Volunteers must not have been vaccinated against HPV (both partners)
  • Any history of cervical, penile, oral or anal cancers
  • Being pregnant or plan on immediately becoming pregnant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01824537

Contacts
Contact: Allita Rodrigues 514-398-8014 allita.rodrigues@mcgill.ca

Locations
Canada, Quebec
McGill University - Division of Cancer Epidemiology Recruiting
Montreal, Quebec, Canada, H2W 1S6
Contact: Allita Rodrigues    514-398-8191    allita.rodrigues@mcgill.ca   
Contact: Candida Pizzolongo    (514) 398-8014    candid.pizzolongo@mcgill.ca   
Principal Investigator: Eduardo L Franco, DrPH         
Sponsors and Collaborators
McGill University
Investigators
Study Director: Kristina Dahlstrom, PhD McGill University
  More Information

No publications provided

Responsible Party: Dr. Eduardo Franco, James McGill Professor and Chair, Department of Oncology; Director, Division of Cancer Epidemiology, McGill University
ClinicalTrials.gov Identifier: NCT01824537     History of Changes
Other Study ID Numbers: CIHR-MOP-125949, IIS #38265
Study First Received: April 1, 2013
Last Updated: March 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by McGill University:
Human papillomavirus (HPV)
Vaccination
Cervical cancer prevention
Herd immunity

Additional relevant MeSH terms:
Warts
Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Tumor Virus Infections
Neoplasms
Skin Diseases, Infectious
Skin Diseases

ClinicalTrials.gov processed this record on April 17, 2014