Vaginal Sildenafil for Primary Dysmenorrhea

NCT07508358 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: SILDYS-OL-02IRB2026-0078
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dysmenorrhea; Menstrual Pain; Endometriosis; Uterine Fibroid

Keywords

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

Outcome Measures

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.

  Baseline (pre-dose) and approximately 4 hours after dosing

Secondary Outcomes (7)

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

  Baseline (pre-dose) through approximately 4 hours after dosing

• Plasma sildenafil concentration

  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

  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

  Baseline (pre-dose), approximately 2 hours after dosing, and approximately 4 hours after dosing

• Change from baseline in diastolic blood pressure

  Baseline (pre-dose), approximately 2 hours after dosing, and approximately 4 hours after dosing

Other Outcomes (1)

• Correlation between change in uterine contraction count and change in menstrual pain intensity

  Baseline (pre-dose) and approximately 4 hours after dosing

Study Arms (1)

Open-label vaginal sildenafil

EXPERIMENTAL

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

Interventions

Sildenafil citrate vaginal suppository DRUG

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

Open-label vaginal sildenafil

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 dysmenorrhea
• Regular menstrual cycles of approximately 21 to 35 days
• Willing and able to complete a single menstrual treatment visit
• Able to comply with study procedures, including MRI procedures and vaginal self-administration of study product
• Able to provide informed consent

You may not qualify if:

• 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
• Use of another phosphodiesterase type 5 inhibitor
• Use of any alpha-adrenergic blocker or any antihypertensive medication
• Uncontrolled hypertension, defined as systolic blood pressure at or above 140 mmHg or diastolic blood pressure at or above 90 mmHg
• Near-hypotension, defined as systolic blood pressure at or below 95 mmHg or diastolic blood pressure at or below 65 mmHg
• Cardiovascular disease
• Clinically significant electrocardiographic abnormality, as judged by the investigator
• Clinically significant laboratory abnormality, as judged by the investigator
• Hepatic impairment of any severity, assessed by screening hepatic laboratory testing and clinical history
• Severe renal impairment
• Platelet count below 100,000 per microliter or hemoglobin below 10 g/dL on screening complete blood count
• Bleeding disorder

Sponsors & Collaborators

• Kevin Hellman: lead

Study Sites (1)

Evanston Hospital

Evanston, Illinois, 60201, United States

Location

MeSH Terms

Conditions

Dysmenorrhea; Endometriosis; Leiomyoma; Pelvic Pain

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

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: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Research Scientist

Model Details: All participants receive a single open-label 100 mg vaginal dose of sildenafil citrate during one menstrual treatment visit. There is no placebo, no comparator group, and no randomization. Each participant serves as her own control, and the primary comparison is the within-participant change from pre-dose baseline.

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 25, 2026

Record last verified: 2026-09

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)