Vaginal Sildenafil for Primary Dysmenorrhea
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexFemale
Age18-35
SponsorKevin Hellman
About this trial
This open-label, non-randomized mechanistic study will evaluate whether a single 100 mg vaginal sildenafil citrate suppository reduces uterine hypercontractility during menstruation in adults with moderate-to-severe dysmenorrhea. Ten participants will each receive one open-label dose during a single menstrual treatment visit and will serve as their own control: 6 participants with primary dysmenorrhea and no evidence of pelvic pathology, plus a separately analyzed exploratory subset of 4 participants, 2 with known endometriosis and 2 with known uterine fibroids. Uterine contractility will be measured with cine magnetic resonance imaging (MRI) before dosing and approximately 4 hours after dosing. Additional objectives are to evaluate acute menstrual pain over the 4-hour observation window, to document systemic exposure using sparse plasma sampling at approximately 2 and 4 hours after dosing, and to assess short-term safety and local tolerability.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female sex assigned at birth
Age 18 to 35 years
History of moderate-to-severe dysmenorrhea
Regular menstrual cycles of approximately 21 to 35 days
Disqualifiers
Gross pelvic pathology identified by clinical history or by the prespecified review of the baseline research MRI. This criterion does not apply to participants enrolled in the prespecified exploratory cohort with known endometriosis or known uterine fibroids, who are analyzed separately.
Known hypersensitivity to sildenafil or any formulation component
Use of nitrates or nitric oxide donors
Use of any CYP3A4 inhibitor or inducer, including dietary sources such as grapefruit
Trial design
Design model
Single group
Treatments tested in this trial
Sildenafil citrate vaginal suppository
DrugA single 100 mg vaginal sildenafil citrate suppository, compounded in an emulsifying MBK base, is self-administered once during the menstrual treatment visit. Treatment is open-label and known to participants and study staff.
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Open-label vaginal sildenafilExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change from baseline in number of uterine contractions during a 10-minute cine MRI acquisition
Uterine contractility will be quantified as the number of uterine contractions observed during a standardized 10-minute cine MRI acquisition. The primary analysis is the within-participant change from pre-dose baseline after a single open-label 100 mg vaginal dose of sildenafil citrate. A decrease indicates reduced uterine contractility.
Time frame
Baseline (pre-dose) and approximately 4 hours after dosingSecondary outcomes
1
Menstrual pain intensity AUC from 0 to 4 hours measured by 100-mm visual analog scale
Menstrual pain intensity will be recorded using a 100-mm visual analog scale, where 0 indicates no pain and 100 indicates worst imaginable pain. Ratings are obtained pre-dose and at approximately 2 and 4 hours after dosing. Area under the curve from 0 to 4 hours will be calculated using the trapezoidal method; lower values indicate lower overall pain burden.
Time frame
Baseline (pre-dose) through approximately 4 hours after dosing2
Plasma sildenafil concentration
Venous plasma sildenafil concentration will be measured to document whether measurable systemic exposure occurs after vaginal administration. Sampling is sparse by design; formal pharmacokinetic parameters such as Cmax, Tmax, AUC, and terminal half-life will not be derived in this study.
Time frame
Approximately 2 and 4 hours after dosing in all participants; additionally approximately 24 hours after dosing in an exploratory subset of 2 participants3
Plasma N-desmethyl sildenafil concentration
Venous plasma concentration of the active N-desmethyl metabolite of sildenafil will be measured to document whether measurable systemic exposure occurs after vaginal administration. Sampling is sparse by design; formal pharmacokinetic parameters such as Cmax, Tmax, AUC, and terminal half-life will not be derived in this study.
Time frame
Approximately 2 and 4 hours after dosing in all participants; additionally approximately 24 hours after dosing in an exploratory subset of 2 participants4
Change from baseline in systolic blood pressure
Hemodynamic tolerability will be assessed by change from pre-dose baseline in systolic blood pressure measured during the treatment visit.
Time frame
Baseline (pre-dose), approximately 2 hours after dosing, and approximately 4 hours after dosingOther outcomes
1
Correlation between change in uterine contraction count and change in menstrual pain intensity
An exploratory mechanistic analysis will evaluate whether attenuation of uterine hypercontractility is associated with reduction in menstrual pain intensity during the acute observation window. The measure is the Spearman rank correlation coefficient between the within-participant change from pre-dose baseline in uterine contraction count on cine MRI and the within-participant change from pre-dose baseline in menstrual pain intensity on a 100-mm visual analog scale, both assessed at approximately 4 hours after dosing. Both changes are calculated as the post-dose value minus the pre-dose value, so a reduction is a negative change. The coefficient ranges from -1 to 1; a positive value indicates that larger reductions in contraction count accompany larger reductions in pain.
Time frame
Baseline (pre-dose) and approximately 4 hours after dosingSponsors and contacts
Click on the lead sponsor to view all of their trials.
Kevin Hellman
Lead sponsor
Endeavor Health
Sponsor institution
Source ClinicalTrials.gov
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