Vaginal Sildenafil for Primary Dysmenorrhea (SILDYS)

Kevin Hellman

Status and phase: Not yet enrolling; Phase 1

Conditions: Menstrual Pain; Dysmenorrhea

Treatments: Drug: Sildenafil citrate vaginal suppository; Drug: Placebo vaginal suppository

Study type: Interventional

Funder types: Other

Identifiers

NCT07508358

SILDYS-RCT-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

Vaginal sildenafil

Experimental group

Description:

Participants receive a single 100 mg vaginal sildenafil citrate suppository during one menstrual treatment visit. In the crossover design, the same participants receive matching placebo during the other menstrual treatment visit.

Treatment:

Drug: Sildenafil citrate vaginal suppository

Placebo

Placebo Comparator group

Description:

Participants receive a single matched placebo vaginal suppository during one menstrual treatment visit. In the crossover design, the same participants receive vaginal sildenafil during the other menstrual treatment visit.

Treatment:

Drug: Placebo vaginal suppository