Trial of treatment and follow-up of vaginal intraepithelial neoplasia (VAIN)

ISRCTN ISRCTN45751386
DOI https://doi.org/10.1186/ISRCTN45751386
EudraCT/CTIS number 2012-005377-31
Secondary identifying numbers 3108
Submission date
04/03/2013
Registration date
15/04/2013
Last edited
11/09/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Human papillomavirus (HPV) can cause cervical, vaginal and vulvar dysplasias (abnormal developments) which usually are diagnosed with a Pap smear. The majority of dysplasias caused by HPV will spontaneously regress, but a prolonged infection (continuing for years) can lead to cancer. Vaginal dysplasias (vaginal intraepithelial neoplasia, VAIN, grades 1-3) are usually treated with laser ablation or surgically with partial vaginal resection. The dysplasias are very commonly long-lasting and treatment often needs to be repeated several times every six months. The treatment can be very challenging due to commonly observed multifocal lesions. Mild dysplasias (VAIN 1) can be followed up to two years prior to treatment, because spontaneous regression commonly happens. It has also been proposed that taking punch biopsies promotes spontaneous regression, because it may stimulate immune response. Topical imiquimod is used for treatment of genital warts (condyloma). Genital warts are benign lesions caused by certain types of HPV. Imiquimod acts as an immunomodulator and it promotes the body’s immune response. Imiquimod has previously been studied in the treatment of other genital lesions caused by HPV such as vulvar, vaginal and cervical dysplasias and the results have been promising. Vaginally administered imiquimod has been found to be quite well tolerated. Possible side effects include a burning local sensation, lower abdominal pain or cold like symptoms and fever. We are conducting a study to compare different treatment options for VAIN.

Who can participate?
We are recruiting patients who are referred to or are already being treated at Helsinki University Central Hospital’s Women’s clinic for VAIN1 that has persisted over two years or recently diagnosed VAIN 2-3. Patients need to be over 18 years of age. We exclude patients who are pregnant or breastfeeding, premenopausal patients without reliable contraception, patients who are simultaneously in need for treatment for a cervical dysplasia, have a known allergy to imiquimod, have difficulty understanding Finnish or English, are HIV positive or have been diagnosed with vaginal carcinoma.

What does the study involve?
Patients referred to colposcopy (the procedure during which a cervix is examined using a colposcope) for VAIN will be enrolled in the study after informed consent. Patients will be randomly allocated to one ofthree groups: follow-up, laser treatment or treatment with topical imiquimod (self-administered 12.5 mg dose 1-2 times a week for 2 months). During colposcopy routine tests include a Pap smear and punch biopsies of detected lesions, additional testing will be done to test for high risk HPV types (hrHPV). Follow-up at the colposcopy clinic will happen 4, 8 and 16 weeks after the primary visit. If VAIN 2-3 persists, patients will be referred to other treatment options and have a control colposcopy at 24 weeks.

What are the possible benefits and risks of participating?
Benefits of participating include a more intensive follow-up scheme than usual and some additional testing. Patients may benefit from alternative treatment options than the current standard treatment. The results of additional testing are available to the patient upon request. Participating in the study is thought to have minimal risks for the patient. Patients in the imiquimod group might experience side effects from the medication, but the dosage can be halved if necessary. The study period is short (4 months) when taking into consideration the risk of the dysplasia progressing and thus participating in the study will not postpone significantly treatment if treatment method needs to be changed at the end of the study period.

Where is the study run from?
The study is run from and performed at the Women’s clinic of Helsinki University Central Hospital (HUCH), Finland.

When is the study starting and how long is it expected to run?
December 2012 to May 2015.

Who is funding the study?
Helsinki University Central Hospital (Finland).

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

Contact information

Dr Annika Riska
Scientific

BO 610
00290 HUS
Helsinki
00290
Finland

Email annika.riska@hus.fi

Study information

Study designRandomized controlled three-arm trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet (Finnish and English).
Scientific titleRandomized trial of treatment and follow-up of vaginal intraepithelial neoplasia (VAIN)
Study objectivesThe aim is to evaluate the effectiveness, tolerability and success rates of different treatment options for VAIN with laser treatment or topical imiquimod. We will also evaluate the so called biopsy effect meaning the possible effect that taking punch biopsies has on promoting spontaneous healing.
Ethics approval(s)University of Helsinki Institutional Review Board, 19/12/2012, ref: 385/13/03/03/2012
Health condition(s) or problem(s) studiedVaginal intraepithelial neoplasia (VAIN)
InterventionGroup A: Follow-up with colposcopy, Pap smear, punch biopsy and hrHPV test 0, 4, 8 and 16 weeks.
Group B: Laser treatment and follow-up with colposcopy, punch biopsy and hrHPV test 4, 8 and 16 weeks.
Group C: Topical imiquimod treatment and follow-up with colposcopy, punch biopsy and hrHPV test 4, 8 and 16 weeks. First two treatment weeks patients in the imiquimod group will self-administer 12.5 mg of imiquimod vaginally in a single dose. During study weeks three to eight they will apply 12.5 mg of imiquimod twice a week 3-4 days apart.

Patients from all study groups will be referred to laser treatment, surgical treatment or other treatment options after 16 weeks if VAIN2-3 persists or has progressed. These patients will have an additional control colposcopy at 24 weeks.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)imiquimod
Primary outcome measureHistological regression to VAIN1 or less within 4 weeks of the end of treatment (week 16) will be considered a positive outcome.
Secondary outcome measures1. Complete histological regression
2. HPV-negativity (week 24)
3. Good tolerability of the treatment
Overall study start date19/12/2012
Completion date15/09/2015

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participants30
Key inclusion criteria1. A biopsy-confirmed VAIN1 that has persisted for two years or biopsy-confirmed VAIN2-3
2. Previously laser or surgically treated VAIN, when previous treatment has occurred over 1 month prior
3. Immune compromised patients (i.e. patients with rheumatoid arthritis, scleroderma, etc.) who frequently have VAIN
4. Patients of legal age (18 years old and above)
Key exclusion criteria1. Vaginal carcinoma
2. Pregnancy or breast-feeding
3. Lack of reliable contraception in premenopausal patients
4. Known allergy to imiquimod
5. Language difficulties (patients who do not speak sufficient Finnish or English)
6. Simultaneous need for Loop Electrosurgical Excision Procedure (LEEP)
7. HIV positive
Date of first enrolment19/12/2012
Date of final enrolment01/05/2015

Locations

Countries of recruitment

  • Finland

Study participating centre

BO 610
Helsinki
00290
Finland

Sponsor information

Helsinki University Central Hospital (Finland)
Hospital/treatment centre

c/o Dr. Annika Riska
Women's clinic
BO 610
HUS
Helsinki
00290
Finland

Email annika.riska@hus.fi
Website http://www.hus.fi/
ROR logo "ROR" https://ror.org/02e8hzf44

Funders

Funder type

Hospital/treatment centre

Helsinki University Central Hospital (Finland)

No information available

Results and Publications

Intention to publish date31/12/2015
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planTo be confirmed at a later date
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 15/11/2016 Yes No

Editorial Notes

11/09/2017: Publication reference added.
On 04/11/2015 the overall trial end date was changed from 31/12/2015 to 15/09/2015.