Vaginal Sildenafil for Primary Dysmenorrhea

NCT07508358 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SILDYS-RCT-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dysmenorrhea; Menstrual Pain

Keywords

sildenafil; vaginal sildenafil; uterine contractility; cine MRI; dysmenorrhea; pelvic pain

Outcome Measures

Primary Outcomes (1)

• Change from baseline in uterine contractions measured by cine MRI

  Uterine contractility will be quantified as the number of uterine contractions observed during a standardized 10-minute cine MRI acquisition. The primary analysis will compare the within-participant change from baseline after vaginal sildenafil versus placebo in the 2-period crossover design.

  Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit

Secondary Outcomes (4)

• Menstrual pain intensity AUC from 0 to 4 hours measured by 100-mm visual analog scale

  Baseline through approximately 4 hours after dosing during each treatment visit

• Plasma sildenafil concentration

  Approximately 4 hours after dosing during each treatment visit

• Change from baseline in systolic blood pressure

  Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit

• Change from baseline in diastolic blood pressure

  Baseline, approximately 2 hours after dosing, and approximately 4 hours after dosing during each treatment visit

Other Outcomes (2)

• Treatment-emergent adverse events and local vaginal tolerability

  From study drug administration through 24 hours after each treatment visit

• Association between change in uterine contractility and change in menstrual pain intensity

  Baseline through 4 hours after study drug administration during each menstrual treatment visit

Study Arms (2)

Vaginal sildenafil

EXPERIMENTAL

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.

Drug: Sildenafil citrate vaginal suppository

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo vaginal suppository

Interventions

Sildenafil citrate vaginal suppository DRUG

A single 100 mg vaginal sildenafil citrate suppository compounded in an emulsifying MBK base is administered during one treatment period of the crossover study.

Also known as: Vaginal sildenafil 100 mg

Vaginal sildenafil

Placebo vaginal suppository DRUG

A single matched placebo vaginal suppository without active sildenafil is administered during one treatment period of the crossover study.

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kevin Hellman: lead

Study Sites (1)

Evanston Hospital

Evanston, Illinois, 60201, United States

Location

MeSH Terms

Conditions

Dysmenorrhea; Pelvic Pain

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Frank Tu, MD, MPH

  EndeavorHealth, Department of Obstetrics & Gynecology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Hellman, PhD

CONTACT

847-570-2622; kevin.hellman@endeavorhealth.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, MRI staff, and outcome assessors will remain blinded to treatment assignment. Study drug and placebo will be prepared in identical-appearing blinded containers with codes known only to the statistician and research pharmacy.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Research Scientist

Model Details: Participants will receive sildenafil during one menstrual treatment visit and matching placebo during a second treatment visit in the subsequent menstrual cycle, or the reverse sequence, according to randomized treatment order.

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 2, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be available beginning approximately 6 months after publication of the primary results and will remain available indefinitely.
• Access Criteria: Access to de-identified individual participant data and supporting documents will be provided to qualified researchers upon reasonable request and approval of a research proposal by the study investigators. A data use agreement will be required. Data will be shared via a secure, controlled-access mechanism.

Locations

US (1)