Vulvar Disease Clinical Trial
Official title:
Vulvar Vestibulitis Trial: Desipramine-Lidocaine
The Vulvar Vestibulitis Clinical Trial (VVCT) a randomized, placebo-controlled, double blinded clinical trial. We will study the clinical efficacy of four medical treatments for vulvar vestibulitis: topical lidocaine, oral desipramine, combined lidocaine and desipramine, and placebo cream and capsules. Desipramine is a tricyclic antidepressant commonly used by clinicians for treatment of several chronic pain conditions that demonstrates an optimal side effect profile compared to other tricyclic antidepressants. Topical lidocaine has also been found to be beneficial for vulvar vestibulitis treatment in small studies. It is hypothesized that the combined use of oral desipramine and topical lidocaine will be more therapeutically effective than either one by itself and better than placebo.
The Vulvar Vestibulitis Clinical Trial (VVCT) is a randomized, placebo-controlled,
double-blinded clinical trial to study the clinical efficacy of four medical treatments for
vulvar vestibulitis: 1) topical lidocaine, 2) oral desipramine, 3) combined lidocaine and
desipramine, and 4) placebo cream and capsules. The duration of study drug will last 12
weeks with post-intervention follow-up at 6 and 12 months. We plan to enroll 128 subjects
from the university-based clinical program at the University of Rochester (UR).Primary
outcome variable will compare the reported pain of the "Tampon Test" (mean of Weeks -2, -1,
and 0), prior to randomization to the reported pain of "Tampon Test" (mean of Weeks 10, 11,
and 12). The dependent (primary outcome) variable will be defined as the percent change of
mean "Tampon test" pain of Weeks (10, 11, and 12) from Weeks (-2, -1 and 0). The primary
analysis of this 2X2 factorial design will involve fitting an Analysis of Covariance
(ANCOVA) regression model to the percent change of mean "Tampon test" pain with the two
treatment variables as the predictors while adjusting for the covariate age. We will test if
the interaction between the two treatments in the ANCOVA model is significant at the .05
level. If the interaction effect is not significant, it will be dropped from the model and
the conclusion will be drawn from the model with main effects only. If significant, the
model with interactions will be adopted. SAS PROC GLM will be used in the analysis.
In the case of non-significant interaction, the primary analysis will be based on the ANCOVA
model with main effects of treatments and adjusting for age. Since there are two treatments
under investigation, the primary analysis will use the Bonferroni correction, i.e. will set
alpha level of 0.025 (two-sided) to determine statistical significance. The significance of
the main effect of each treatment will be assessed by t-tests in the ANCOVA model. The aim
of the primary analysis is to determine whether each treatment is superior to placebo, and
if both hypotheses hold, the double treatment therapy will be most effective under the
additive effect assumption of the ANCOVA model. The ANCOVA model compares all subjects who
receive that treatment with all subjects who do not, irrespective of whether they receive
the other treatment, after adjusting for the other treatment and age of subject, and is more
powerful in finding individual treatment effects in the study.
If interaction between treatments is significant, the ANCOVA model with interaction will
estimate the treatment effects for each of the four groups. This model is able to test all 6
contrasts between the four combinations. A hierarchical (gatekeeping) testing strategy to
maintain a family-wise error rate will be adopted as the following: the first stage will
compare desipramine or lidocaine individually to placebo with multiplicity-adjusted
p-values. If a significant difference (one or both null hypotheses rejected) is found for
either or both individual agents, then the analysis will proceed to the second-stage of
hypothesis which will compare the effects of the active desipramine/active lidocaine
treatment to the double placebo. If a significant difference (null hypothesis rejected) is
found for combined therapy over placebo based on the multiplicity-adjusted p-value, then the
final (tertiary) stage of comparison will be performed comparing combined therapy to
individual therapy. In the hierarchical (gatekeeping) testing procedures, inferences in each
stage depend on the acceptance or rejection of null hypotheses in all previously stages, and
each stage serves as a gatekeeper for the stages later in the sequence. In our strategy for
the model with significant interaction effect, if at least one hypothesis has been rejected,
then the next stage of hypotheses will be tested, and the family-wise error rate is
controlled at the .05 level.
Secondary analyses will include subset analysis, comparison of the double-active treatment
group against the others (placebo and the single-treatment groups) on percent change of mean
"Tampon test" as well as standardized pain measures such as the Brief Pain Inventory and the
McGill Pain Questionnaire. This is to explore if the active desipramine/active lidocaine
treatment has more advantages that may not be shown in the ANCOVA model. The secondary
analysis is to explore supportive evidence to the primary objective of this trial, and no
confirmatory conclusions are needed. In the secondary analysis, confidence intervals and
statistical tests are of exploratory nature and no claims are intended.
Primary and secondary outcome variables will be analyzed according to a modified "intention
to treat" with "last observation carried forward". The sample analyzed for the primary
outcome will include the first three or fewer pre-randomization Tampon Test measures and the
last three or fewer post-randomization Tampon Test measures, up to and including study Week
12. The subject sample analyzed for drug safety/side effects will include all subjects who
have taken at least one dose of study drug.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT02881229 -
Vulvar Mucosal Specialty Clinic Chart Review
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