A Phase 1 interventional study of Sildenafil citrate vaginal suppository in Dysmenorrhea, Menstrual Pain and Endometriosis, sponsored by Kevin Hellman. Not yet recruiting at 1 site in United States. Open to female participants aged 18 Years to 35 Years. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Kevin Hellman · Phase 1, Interventional, and Basic science
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.
Dysmenorrhea is believed to be driven in part by excessive uterine contractility. Sildenafil, a phosphodiesterase-5 inhibitor, may reduce myometrial hypercontractility through enhanced nitric oxide-cGMP signaling. Prior vaginal sildenafil data suggested acute pain relief, but mechanism and systemic exposure were not well characterized.
This study is a mechanistic biomarker investigation in which uterine contractility measured by cine MRI serves as a functional pharmacodynamic marker of PDE5 inhibition. Participants complete a screening visit (medical history, vital signs, 12-lead ECG, screening laboratory tests, MRI safety screening, questionnaires) and a gynecologic examination visit before dosing. When a participant is menstruating and reporting cramping pain of at least 5 on a 0 to 10 scale, she attends a single treatment visit of approximately 6 hours. At that visit she undergoes a pre-dose cine MRI, self-administers a single 100 mg vaginal sildenafil citrate suppository, and undergoes a repeat MRI at approximately 4 hours after dosing. No MRI is obtained at the 2-hour timepoint. Pain ratings on a 100-mm visual analog scale, vital signs, adverse event assessment, and venous blood samples for plasma sildenafil and its N-desmethyl metabolite are obtained at approximately 2 and 4 hours after dosing. In a prespecified exploratory subset of 2 participants, an additional plasma sample is obtained at approximately 24 hours after dosing at a brief return blood-draw visit. Menstrual effluent is collected during the visit. Electronic side-effect questionnaires are sent at 6 and 24 hours after dosing, and a second gynecologic examination visit occurs within approximately one month after the treatment visit.
There is no placebo and no comparator group. The primary analysis is the within-participant change from pre-dose baseline in the number of uterine contractions during a standardized 10-minute cine MRI acquisition. The planned population of 10 participants comprises 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).
Plasma sampling in this study is deliberately sparse because participants are in acute menstrual pain. Formal pharmacokinetic parameters such as Cmax, Tmax, area under the concentration-time curve, and terminal half-life will not be derived from this study; the samples are intended to document whether measurable systemic exposure occurs after vaginal administration and to relate exposure to hemodynamic and adverse event outcomes.
Exclusion Criteria:
All participants receive a single open-label 100 mg vaginal sildenafil citrate suppository during one menstrual treatment visit, self-administered after the pre-dose MRI. Uterine contractility, pain ratings, vital signs, and plasma concentrations are assessed before and after dosing within the same visit.
Drug: Sildenafil citrate vaginal suppository
A 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.
Also known as: Vaginal sildenafil 100 mg
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 dosing
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 dosing
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 participants
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 participants
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 dosing
Change from baseline in diastolic blood pressure
Hemodynamic tolerability will be assessed by change from pre-dose baseline in diastolic blood pressure measured during the treatment visit.
Time frame: Baseline (pre-dose), approximately 2 hours after dosing, and approximately 4 hours after dosing
Change from baseline in heart rate
Hemodynamic tolerability will be assessed by change from pre-dose baseline in heart rate measured during the treatment visit.
Time frame: Baseline (pre-dose), approximately 2 hours after dosing, and approximately 4 hours after dosing
Number of participants with treatment-emergent adverse events, including local vaginal tolerability findings
Adverse events and symptoms potentially related to PDE5 inhibition or vaginal administration, including headache, flushing, dizziness or lightheadedness, visual disturbances, palpitations, syncope, vaginal irritation, local discomfort, abnormal discharge, and acute changes in bleeding, will be collected during the treatment visit, by electronic side-effect questionnaires at 6 and 24 hours after dosing, and at the post-treatment gynecologic examination visit.
Time frame: From study drug administration through the post-treatment gynecologic examination, up to approximately 1 month after dosing
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 dosing
Plan to share: Yes — De-identified individual participant data underlying the results reported in this study will be shared. This includes: * Participant-level demographic and baseline characteristics (e.g., age, menstrual history, eligibility variables) * Visit-level and timepoint-level indicators for the open-label dosing visit * Primary outcome data: number of uterine contractions during the standardized 10-minute cine MRI acquisition at baseline and approximately 4 hours after dosing * Plasma sildenafil and N-desmethyl sildenafil concentrations * Adverse event and safety monitoring data * Derived variables and analysis datasets used to generate reported results Data will be shared in a de-identified format consistent with applicable privacy regulations.
Supporting information: Study protocol, Sap, Icf, Analytic code
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