DysmenorrheaPhase 1SILDYSNCT07508358
Vaginal Sildenafil for Primary Dysmenorrhea
A Phase 1 study testing Sildenafil citrate vaginal suppository in people with Dysmenorrhea and Menstrual Pain, run by Kevin Hellman at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Dysmenorrhea, Menstrual Pain, Endometriosis
- What is being tested?
- Sildenafil citrate vaginal suppository
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to Jul 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Peptic ulcer disease
- History of non-arteritic anterior ischemic optic neuropathy, risk factors for non-arteritic anterior ischemic optic neuropathy, or other retinal disorders
- Sickle cell disease
- Active pelvic infection
- Presence of an intrauterine device, because of MRI artifact affecting interpretability
- Other contraindication to MRI or factors that would impair MRI safety or interpretability, including certain metallic implants, metallic injury, or claustrophobia
- Pregnant or breastfeeding
- Any condition that, in the opinion of the investigator, would increase risk or interfere with study participation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Evanston Hospital
Evanston, Illinois, 60201
Frank Tu, MD, MPH, 847-644-0494, frank.tu@endeavorhealth.org
Kevin Hellman, PhD, 847-570-2622, kevin.hellman@endeavorhealth.org
About this study
Official title: Vaginal Sildenafil for Primary Dysmenorrhea: An Open-Label Mechanistic Study
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.
Read the 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 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.
- Conditions
- Dysmenorrhea, Menstrual Pain, Endometriosis, Uterine Fibroid
- Being tested
- Sildenafil citrate vaginal suppository
- Keywords
- sildenafil, vaginal sildenafil, uterine contractility, cine MRI, dysmenorrhea, pelvic pain
- Medical subject headings
- Dysmenorrhea, Endometriosis, Leiomyoma, Pelvic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil citrate vaginal suppositoryDrug
Also called Vaginal sildenafil 100 mg
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Sildenafil citrate vaginal suppository |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From study drug administration through the post-treatment gynecologic examination, up to approximately 1 month after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2026
- Study start1 Oct 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DysmenorrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kevin Hellman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kevin Hellman, Endeavor Health
- Investigators
- Frank Tu, MD, MPH, Principal investigator, EndeavorHealth, Department of Obstetrics & Gynecology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07508358
- Sponsor's protocol ID
- SILDYS-OL-02
- Other IDs
- IRB2026-0078
- Acronym
- SILDYS
- Status last verified
- Sep 2026
- First submitted
- 26 Mar 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.