Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02712814 |
| Other study ID # |
0152-15-COM1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 30, 2016 |
| Est. completion date |
August 2021 |
Study information
| Verified date |
April 2022 |
| Source |
Meir Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The proposed study will evaluate a clinical algorithm for the diagnosis and treatment of
provoked vestibulodynia (PVD). The algorithm, distinguishes between four subtypes of PVD:
hormonally mediated PVD, hypertonic pelvic floor dysfunction, congenital neuroproliferative
PVD and acquired neuroproliferative PVD, based on a patient's history and physical exam. The
study will follow patients diagnosed with PVD, for one year, and evaluate the treatment
outcome in the different subgroups. Investigators hope that conducting a prospective study,
showing clinical benefit and improved outcome for patients classified according to this
method may change the common practice of "trial and error" based treatment, and will improve
clinical results.
Description:
Background Provoked vestibulodynia (PVD) is the term describing a syndrome of provoked,
localized allodynia of the vestibule of the vulva, not explained by another condition, and
lasting more than 3 months. PVD is not a defined disease but rather a symptom. It is thought
that PVD represent a group of distinct disorders that have been classified together because
they produce pain in the same anatomic location. Causes of these disorders include hormonal
imbalance, mainly caused by hormonal contraception, nerve fiber proliferation in the
vestibular mucosa and hypertonic pelvic floor dysfunction. PVD may appear with sexual debut
or first attempts to insert a tampon (primary PVD) or can be a new onset of pain with
activities that did not previously illicit pain (secondary PVD).
Studies found that different factors such as genetic, inflammatory mediators, recurrent
vaginitis, allergy and trauma may be involved in the development of PVD. A high percentage of
patients with vulvar pain report an antecedent history of vulvovaginal candida infection,
although it is unknown if this represents a true increase in incidence or a misdiagnosis. It
has been suggested that repeated vulvovaginal infections are a triggering event for some
women leading to chronic vulvar pain. This observation has led to hypothesis that in patients
with neurogenic vulnerability, an initiating event or series of events may lead to chronic
vulvar pain.
Treatment of vulvodynia is generally predicated on a trial and error basis, because the
pathogenesis is not defined. The result is that many forms of therapeutic interventions have
been used, yet the evidence remains largely inconclusive, the response rate varies between
40-85%, and many women do not respond to any of the treatments. Unfavorable outcomes to
therapy can be explained by grouping patients with different conditions under one diagnosis,
and then studying an intervention that might only help one subset of the conditions. This can
lead to an apparent lack of effect, due to dilution of the patient subpopulations.
A different approach to diagnosis and treatment of PVD was suggested by Dr. Andrew Goldstein.
He classifies PVD into groups, based on history and examination findings:
1. Hormonally mediated PVD - The pain began while taking hormonal contraceptive or other
medications that affect hormones, after removal of ovaries, breastfeeding or menopause.
Typically, patients have a low calculated free testosterone and complain of dryness and
decreased libido. The entire vestibule is tender and vestibular mucosa is often dry and
thin. Treatment includes stopping hormonal contraception and application of topical
estradiol with testosterone to the vestibule.
2. Hypertonic pelvic muscle dysfunction - In this subgroup, pelvic floor (PF) muscles
become tight and tender. Patients often have other symptoms suggesting hypertonicity
(urinary frequency, urgency and hesitancy, constipation, hemorrhoids and anal fissures),
and predisposing factors, such as musculoskeletal disorders or anxiety may coexist.
Typically, the pain is much worse at 4-8 o'clock position of the vestibule with minimal
or no pain in the upper vestibule. Treatment includes PF physiotherapy, with an optional
addition of muscle relaxants (valium suppositories and Botulinum toxin injections).
3. Neuroproliferative PVD- In this condition, women have an increased number of nociceptors
in the vestibular mucosa. This group is further subdivided into congenital and acquired
forms. In the congenital subgroup, vestibular pain has always been present, and there
may be sensitivity to palpation of the belly button (which is an evidence of a
congenital neuronal hyperplasia within the tissue derived from the urogenital sinus).
With acquired neuroproliferative PVD, the pain may begin after a severe allergic
reaction or vaginitis. There is tenderness of the entire vestibule. Treatments include
topical anaesthetics, antidepressants, antiseizure drugs, capsaicin cream and vulvar
vestibulectomy.
Goldstein's diagnostic algorithm is claimed to allow differentiation between different causes
of PVD. In doing so, appropriate treatments to each subgroup can be selected, and their
success rate should exceed the reported success rate in PVD treatment studies. Although
investigators have a good personal experience with this method, the algorithm is not evidence
based.
Objectives:
The proposed study is a prospective, cohort-based study, which will evaluate the
characteristics of PVD-subgroups according to Goldstein's algorithm, patients' response to
treatment and their outcome.
General aims: Define whether women that have been diagnosed according to Goldstein's
algorithm experience higher rates of favorable outcome in comparison to those reported in the
literature. This will allow us to study the effectiveness of this classification and to
better define the subgroups.
Specific aims:
1. Describe the population of women with PVD attending the clinic, the distribution of
criteria and the characteristics of women in each category.
2. Follow women diagnosed according to algorithm for one year and define treatment success.
Methods The proposed study is a prospective, cohort-based study. Patients will be recruited
from the clinic for vulvovaginal disorders in Clalit Healthcare services in Jerusalem. The
diagnostic procedures, patients' sub-classification and the proposed treatments in the
current protocol are identical to those currently used in the clinic. Patients who fulfill
diagnostic criteria of PVD and who will be willing to participate in the study will be asked
to sign an informed consent and complete self-administered intake questionnaires requesting
data about their PVD condition and its severity, various parameters of quality of life (QOL),
general health, Ob\Gyn history, sexual function, psychometric characteristics (anxiety,
depression etc) and demographics. After completing the questionnaires, each patient will
undergo a standard evaluation, and will be diagnosed according to Goldstein's algorithm.
Instructions for treatment will be given in regards to the diagnosis. Patients will be
instructed to schedule follow-up appointments at 3,6,9, and 12 months. During follow-up
appointments they will be assessed in regard to vestibular tenderness using various
parameters, as well as by questionnaires of QOL and sexual function.
