None listed
Conditions
Brief summary
A randomised, placebo-controlled study looking at the effectiveness of an intravulvo-vaginal cream Lyrica (registered trademark) for treatment of chronic pain in the vulvo-vagina. A research project is being conducted by Professor Chris Benness, Dr Elizabeth Willsteed and Dr Jane Manning to investigate a treatment for chronic vulvo-vaginal pain. Why is the research being done? The purpose of this project is to establish whether a prescription drug, Pregabalin (Lyrica - registered trademark) when applied topically as a vulvo-vaginal cream is a safe and effective means of treating vulvo-vaginal pain. Previous research has suggested that it may be effective. We hope it causes fewer side effects than Pregabalin when taken orally which is a standard treatment for the condition. This drug is not experimental or new, and is approved to treat chronic neuropathic pain. Method: Two creams, A and B will be prepared. One of which will contain pregabalin . Treatment allocation will be double blind and randomized. Participants who satisfy inclusion criteria will apply the cream for 6 weeks with dose adjustment allowed. They will then have the option to receive the active pregabalin cream (open label) for a further 6 weeks if they wish. They will complete questionnaires designed to detect relevant demograohic factors and factors that may potentially confound results. They will complete questionnaires on line or by mail at 0, 2 4 ,6 and 12 weeks. Participants: Those with vulvo-vaginal pain that has stopped tampon use or intercourse or regular internal examination for 6 months or more. Those over 17 Those not pregnant and are not planning to become pregnant (that is, you must be currently using effective contraception) Those with no known allergy to Pregabalin. Those whose pain is not due to cancer or past radiation treatment or to lichen planus or lichen sclerosis, or other treatable causes. Those who have time to participate over 6 weeks and who live within 200 km of Sydney NSW Australia Area Those who don’t have significant kidney disease. What would participants be asked to do? They will need to be available for a minimum of 2 visits over a minimum 6 weeks to assess response to a blinded treatment cream. The first visit will take approximately 1 hour. Participating in the study will involve: A vulvo-vaginal examination at the first visit Attending for a first visit and a possible visit at 2 weeks Completing five (5) Questionnaires which will be provided at visit 1, and again at weeks 2, 4, 6 and also week 12 if they wish to continue. These questions will ask about general health and the nature of the vulvo-vaginal pain. Some of these are sensitive questions asking about sexual function and possible abuse history. They will complete a 24 hour voiding diary (how often you go to the toilet) prior to the first visit. After the initial visit, online questionnaires or postal questionnaires will be possible to complete for all subsequent review, or if they wish they can attend in person. They will collect a study drug package, labelled either A or B at the 1st visit. All participants will apply cream throughout the 6 week study, but the contents of the cream will be either Lyrica (registered trademark) pregabalin or a placebo (not active medication). Participants will not be told which cream they receive. What are the risks and benefits of participating? Benefits Participating in this study may benefit your condition (vulvo-vaginal pain). Risks Although the cream base is neutral - local irritation may still occur Irritation with use of this vulvo-vaginal cream may occur for 14% of women. Sedation may still occur even though it has not been reported using this cream. Tiredness, dizziness, confusion is common with many oral medications used to treat vulvo-vaginal pain. How will privacy be protected? All information gained will be treated confidentially. It will be accessed, used, managed and stored in accordance with the NSW Health Records and Health Information Privacy Act 2002
Interventions
Interventions;
Double Blinded randomized allocation of active Pregabalin(Lyrica- Registered Trademark) or placebo vaginal aqueous cream twice daily for 6 weeks . At 6 weeks the option is provided for open label use of active cream for a further 6 weeks
Randomization
Randomization numbers will be generated by the Epidemiologist and patients will be allocated numbers by a research nurse, in order to keep the chief investigators blinded. Twenty millilitre calibrated syringes of active and placebo c
Interventions; Double Blinded randomized allocation of active Pregabalin(Lyrica- Registered Trademark) or placebo vaginal aqueous cream twice daily for 6 weeks . At 6 weeks the option is provided for open label use of active cream for a further 6 weeks Randomization Randomization numbers will be generated by the Epidemiologist and patients will be allocated numbers by a research nurse, in order to keep the chief investigators blinded. Twenty millilitre calibrated syringes of active and placebo cream will only be labelled as cream A and B. Each syringe will have am identifying number for tracking. * Cream will be applied to vulvo-vaginal area twice daily for 2 weeks initially. It will be kept at room temperature. Dosage of cream will be increased from starting dose at 2 weeks in consultation with the investigator if no response is obtained. Cream will be applied to the point of maximal pain. Participants will be interviewed at 2 weeks. If at or before 2 weeks side effects are experienced- subjects will be instructed to contact the investigator and discuss. Dosage reduction may be initially advised or cessation and a consultation will be organized for reassessment as soon as convenient. A different base such as Glycerine and Sorbelene might then be used. Dosage doubling will be scheduled if there is no response * Further Labelled Pregabalin cream will be provided at 6 weeks if the participant wishes. Treatment will continue for a further 6 weeks (12 weeks in total). Dosage of cream will again be increased 1 week later (i.e. week 7) in consultation with the CI if no response is noted, or reduced , adjusted if side effects are experienced. At the 6 week visit, any remaining cream from the 1st 6 weeks will be retrieved and examined for usage. At the 12 week point - any remaining cream will be retrieved and examined for usage. Patients will be phoned when questionnaires are due to make sure these are completed and that cream is tolerated and being used * The dose (Lyrica registered trademark) Pregabalin will be 2.5% in concentration. This starting dose is equivalent to 25 mg of drug in 1 ml of cream used twice daily. If side effects are initially experienced, half the dose can be used twice daily by drawing up half the initial amount (0.5 ml). If no effect is initially observed, 2 mls can be used twice daily at 2 weeks; ie - dose is doubled. * Participants with significantly impaired renal function will not be recruited to the study (e GFR < 60 or creatinine clearance < 60 mls/min). Those with mildly impaired renal function (e GFR >= 60) will receive the standard dosage but note will be made of this. Maximum oral dosage of (Lyrica registered trademark) Pregabalin is 300 mg . Guidelines suggest the drug is safe orally in those with renal impairment up to an oral dose of 150 mg twice daily. If dosage doubling is required in a participant where mild renal impairment is also present (Cr Cl 30-60 ml/min); a dose adjustment will be calculated by consulting a renal physician for advice. * Subjects will complete a set of standardized questionnaires at regular intervals. The research nurse will remind them by phone. Questionnaires may be completed on line confidentially or posted.
Sponsors
Dr Jane Manning
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
*INCLUSION; Unable to insert tampon or have penetrative vulvo-vaginal intercourse or to tolerate regular vulvo-vaginal examination *There may be also discomfort wearing tight clothing, discomfort sitting, mobilizing *Other causes of pain must have been excluded by swab, biopsy and / or skin scraping if necessary. Participants will be reviewed by a female dermatologist with a clinical and research interest in vaginal pain. Diagnoses of local trauma, scarring, candida, HSV, other dermatoses- lichen simplex etc will only exclude participation if appropriate treatment for these diagnoses has been provided but has not resolved the symptom substantially. * Pain must be present persistently for greater or equal to 6 months * Maximum Pain Severity was / is > 50 on Gra scale 1-100 on greater or equal to 2 occasions in 1 week *Other associated pelvic pain conditions do not exclude inclusion; such as interstitial cystitis/ painful bladder syndrome), endometriosis, rectal pain, provided focal vulvo-vaginal examination is also uncomfortable Can include past use of oral Gabapentin or Pregabaln with or without side effects. Participants may come from clinics at RPAH or from elsewhere
Exclusion criteria
*Vulvo-vaginal or vulval pain of known and effectively treatable cause ie it is not refractory to other treatment *Pregnancy or risk of pregnancy (unprotected intercourse). If risk suspected HCG testing prior to randomization Age 17 or under *Lichen planus/sclerosis will exclude participation *Untreated pelvic malignancy, past or current radiation therapy. *Known allergy to Gabapentin , Pregabalin *Pain present persistently for less than 6 months * If the maximum Pain Severity was never > 50 on Gra scale 1-100 on < 2 occasions in 1 week. *Severe renal impairment (Cr Cl or e GFR < 60) or recent (less than 12 months) acute myocardial infarct. * They live more than 200 km from Sydney
Outcome results
None listed