Trial of treatment of vaginal intraepithelial neoplasia (VAIN)

Plain English Summary

Background and study aims
Human papilloma virus (HPV) is the name used to refer to a group of viruses that can affect the skin and the moist membranes lining the body, for example the cervix, mouth and throat. Genital HPV can cause abnormal tissue growth (lesions) and other changes to cells within the cervix, vagina and vulva. This can sometimes lead to cervical cancer. These abnormalities can usually be detected with a Pap (cervical) smear. The majority of lesions caused by HPV do not need to be treated, but a prolonged infection over a number of years can lead to precancerous changes and eventually cancer. Lesions in the vagina (vaginal intraepithelial neoplasia, VAIN) are usually treated with laser ablation (removal of the lesion using a laser) or surgical removal of the affected part of the vagina. The disease can be chronic (long lasting) requiring repeated treatment. The treatment can also be difficult due to multifocal lesions (lesions in more than one region of the vagina). A cream containing imiquimod is used to treat genital warts locally. Genital warts are lesions caused by certain HPV types and are benign. Imiquimod is an immunomodulator, which means it stimulates the body’s own immune response to the infection. Imiquimod has already been studied in the treatment of other genital lesions caused by HPV. The results have been promising and vaginally administered imiquimod has been relatively well tolerated. This study is looking at different treatment options for vaginal intraepithelial neoplasias (VAIN). The aim of the study is to see how well tolerated and how successful these treatments are.

Who can participate?
Women over 18 that have been diagnosed with VAIN.

What does the study involve?
Participants have an HPV sample taken (with a brush) in addition to routine samples during an outpatient colposcopy visit. They are then randomized into one of two groups. Those in group 1 are treated laser ablation. Those in group 2 are treated with vaginally administered imiquimod. The imiquimod is given as suppositories which are used at home 1-2 times a week for two months (the single dose of imiquimod is 12.5 mg which can be halved if severe side effects occur). The follow-up in the study includes visits at the colposcopy clinic at 2, 4 and 6 months after the initial visit. If persistence or progression of the lesion is detected at the 4-month-visit, the patient is offered either laser ablation or surgery for treatment.

What are the possible benefits and risks of participating?
The frequent follow-ups for the duration of this study can benefit the patients participating. Participation in the study is not likely to cause any harm to the patient even if the treatment method would have to be changed during the course of the study. Due to the short duration of the study no significant delay in treatment will occur. Side effects of imiquimod can be local irritation, lower abdominal pain and flu-like symptoms or fever. These side effects can be treated with non-steroidal anti-inflammatory drugs (NSAIDs).

Where is the study run from?
Helsinki University Hospital, Women's Hospital.

When is the study starting and how long is it expected to run for?
September 2015 to December 2020.

Who is funding the study?
Research Council for Health (Finland)

Who is the main contact?
Dr Annika Riska
annika.riska@hus.fi

Study website

Type

Scientific

Contact name

Dr Annika Riska

ORCID ID

Contact details

Haartmaninkatu 2
Helsinki
00290
Finland
+35894711
annika.riska@hus.fi

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

N/A

Scientific title

Randomized trial of treatment of vaginal intraepithelial neoplasia (VAIN): laser vaporization and imiquimod

Acronym

Study hypothesis

This randomized trial aims to assess the efficacy of treatment of VAIN with traditional laser vaporization or vaginally administered imiquimod. Efficacy will be assessed by histological regression and HPV clearance. We have conducted a pilot trial on this subject (ISRCTN45751386) which found laser and imiquimod treatment to be equally effective in regard to histological regression, but imiquimod was significantly more effective in achieving HPV clearance. This study has power estimations based on the pilot trial.

Ethics approval(s)

Helsinki University Hospital Ethical Committee, 26/11/2015, ref: 339/13/03/03/2015

Study design

Single center randomized interventional trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

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

Condition

Vaginal intraepithelial neoplasia (VAIN)

Intervention

Patients enrolled in the study will have an HPV sample taken (with a brush) in addition to the routine samples during an outpatient colposcopy visit. Enrolled patients will be randomized into two groups:

Group 1: treated by laser ablation
Group 2: treated with vaginally administered imiquimod

The imiquimod is given as suppositories which are used at home 1-2 times a week for two months (the single dose of imiquimod is 12.5 mg which can be halved if severe side effects occur). The follow-up in the study includes visits at the colposcopy clinic at 2, 4 and 6 months after the initial visit. If persistence or progression of the lesion is detected at the 4-month-visit, the patient is offered either laser ablation or surgery for treatment.

Intervention type

Mixed

Primary outcome measure

1. Histological regression (defined as VAIN 1 or less), assessed from punch biopsies
2. HPV clearance, assessed via HPV genotyping from cervical or vaginal brush samples

Measured at 2, 4 and 6 months

Secondary outcome measures

1. Complete histological regression, assessed from punch biopsies
2. Tolerability of treatment, assessed based on adverse effect reporting on a standardized form from the patients

Measured at 2, 4 and 6 months

Overall study start date

01/09/2015

Overall study end date

31/12/2020

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Over 18 years of age
2. Histological diagnosis of VAIN 2-3
3. Histological diagnosis of VAIN 1, which has been expectantly managed for two years

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Female

Target number of participants

Total recruitment target 60 patients.

Participant exclusion criteria

1. Pregnancy or lactation
2. Lack of reliable contraception in premenopausal patients
3. Known HIV infection
4. Vaginal cancer

Recruitment start date

01/01/2016

Recruitment end date

31/12/2020

Countries of recruitment

Finland

Study participating centre

Helsinki University Hospital, Women's Hospital
Helsinki
00610
Finland

Organisation

Helsinki University Hospital, Women's Hospital

Sponsor details

Haartmaninkatu 2
Helsinki
00290
Finland
+35894711
annika.riska@hus.fi

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/02e8hzf44

Funder type

Research council

Funder name

Terveyden Tutkimuksen Toimikunta

Alternative name(s)

Research Council for Health, Forskningsrådet för Hälsa

Funding Body Type

private sector organisation

Funding Body Subtype

Universities (academic only)

Location

Finland

Publication and dissemination plan

We intend to publish results of the outcome measures when the trial is completed.

Intention to publish date

31/12/2021

Individual participant data (IPD) sharing plan

IPD sharing plan summary

Available on request

Study outputs