Vaginal Sildenafil for Primary Dysmenorrhea

Official title

Vaginal Sildenafil for Primary Dysmenorrhea: A Randomized, Double-Blind, Placebo-Controlled, Two-Period Crossover Mechanistic Study

Overview

This phase 1 randomized, double-blind, placebo-controlled, two-period crossover trial will evaluate whether a single 100 mg vaginal sildenafil citrate suppository reduces uterine hypercontractility during menstruation in adults with moderate-to-severe dysmenorrhea. Uterine contractility will be measured using cine magnetic resonance imaging (MRI). Key secondary objectives are to evaluate acute menstrual pain reduction over 4 hours, characterize limited systemic exposure using a single 4-hour plasma sildenafil concentration, and assess short-term safety and tolerability.

Detailed description

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 mechanistic target-engagement study uses a randomized, double-blind, placebo-controlled, two-period crossover design. Participants will complete a screening visit and two menstrual treatment visits during separate cycles. At each treatment visit, participants with active menstrual pain will undergo baseline MRI, self-administer either vaginal sildenafil citrate 100 mg or matching placebo, and then complete repeat MRI assessments approximately 2 and 4 hours after dosing. Pain ratings, vital signs, adverse event assessments, pregnancy testing, and a single 4-hour blood draw for plasma sildenafil concentration will be obtained. Menstrual effluent samples will also be collected.

The primary objective is to determine whether vaginal sildenafil produces measurable reductions in uterine hypercontractility during menstruation. Secondary objectives are to evaluate the effect of treatment on menstrual pain intensity over the 4-hour observation window, assess systemic exposure after vaginal administration, and characterize short-term hemodynamic and clinical tolerability.

Interventions

• Drug Sildenafil citrate vaginal suppository
  A single 100 mg vaginal sildenafil citrate suppository compounded in an emulsifying MBK base is administered during one treatment period of the crossover study.
• Drug Placebo vaginal suppository
  A single matched placebo vaginal suppository without active sildenafil is administered during one treatment period of the crossover study.

Primary outcome measures

• Change from baseline in uterine contractions measured by cine MRI [Time frame: Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit]

Secondary outcome measures (4)

• Menstrual pain intensity AUC from 0 to 4 hours measured by 100-mm visual analog scale [Time frame: Baseline through approximately 4 hours after dosing during each treatment visit]
• Plasma sildenafil concentration [Time frame: Approximately 4 hours after dosing during each treatment visit]
• Change from baseline in systolic blood pressure [Time frame: Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit]
• Change from baseline in diastolic blood pressure [Time frame: Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit]

Eligibility criteria

Inclusion criteria

• Female sex assigned at birth
• Age 18 to 35 years
• History of moderate-to-severe primary dysmenorrhea
• Regular menstrual cycles of approximately 21 to 35 days
• Willing and able to complete 2 menstrual treatment visits in separate menstrual cycles
• Able to provide informed consent
• Able to comply with study procedures, including MRI procedures and vaginal self-administration of study product

Exclusion criteria

• Known hypersensitivity to sildenafil or any formulation component
• Current use of nitrates or nitric oxide donors
• Current use of potent CYP3A4 inhibitors or potent CYP3A4 inducers
• Current use of another phosphodiesterase type 5 inhibitor
• Uncontrolled hypertension, near-hypotension, or other clinically significant hemodynamic instability
• Clinically significant cardiovascular disease
• Clinically significant electrocardiographic abnormality, as judged by the investigator
• Clinically significant laboratory abnormality, as judged by the investigator
• Severe hepatic impairment or severe renal impairment
• Active pelvic infection
• Contraindication to MRI or factors that would impair MRI safety or interpretability, including certain metallic implants, metallic injury, claustrophobia, or intrauterine device-related artifact
• Pregnant or breastfeeding
• Any condition that, in the opinion of the investigator, would increase risk or interfere with study participation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Evanston Hospital — Evanston

Identifiers

NCT: NCT07508358 · SILDYS-RCT-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗