Chronic Musculoskeletal PainPhase 2PEACENCT07868536
Post-traumatic Estradiol Administration and Care Evaluation (PEACE)
A Phase 2 study testing 17β-estradiol in people with Chronic Musculoskeletal Pain and Sexual Assault, run by University of North Carolina, Chapel Hill.
Trial summary
This pilot randomized, double-blind, placebo-controlled trial evaluates the feasibility, acceptability, and tolerability of administering a single 6 mg oral dose of 17β-estradiol (E2) to individuals assigned female at birth who have experienced a sexual assault (SA) within the previous 120 hours. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Chronic Musculoskeletal Pain, Sexual Assault, Posttraumatic Stress Disorder (PTSD)
- What is being tested?
- 17β-estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 28 Sep 2026to 31 Jul 2028
- Phase
- Phase 2
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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18 to 45 years
- Assigned female at birth
- Experienced a sexual assault within the previous 120 hours and able to complete an in-person study visit within 120 hours of the assault
- Able to read and speak English
- Able to provide informed consent
Who cannot join
- Pregnant or currently breastfeeding
- Currently taking an estrogen-containing medication
- Current or prior diagnosis of hypertension
- Use of anticoagulant medications (e.g. aspirin, heparin, warfarin, enoxaparin, dalteparin, tinzaparin, apixaban, rivaroxaban, dabigatran, edoxaban)
- Current or prior cardiomyopathy; history of heart attack or heart valve disease
- History of deep venous thrombosis or pulmonary embolism, or genetic predisposition to clots (thrombophilia)
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- Sickle cell disease
- History of stroke
- Migraines with aura
- Vascular disease due to diabetes, or diabetes of more than 20 years duration
- Chronic kidney disease (including nephrotic syndrome or dialysis)
- Acute hepatitis; history of liver tumors
- History of cholestasis (unless pregnancy-related only)
- Gallbladder disease (unless treated by cholecystectomy)
- History of systemic lupus erythematosus
- History of breast or endometrial cancer
- Opioid use exceeding 30 mg daily oral morphine equivalents per day
- Smokes more than 15 cigarettes per day
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial of Single-Dose Oral 17β-Estradiol Administered Within 120 Hours of Sexual Assault to Evaluate Feasibility, Acceptability, and Preliminary Effects on Chronic Musculoskeletal Pain and PTSD Over the Following Three Months
This pilot randomized, double-blind, placebo-controlled trial evaluates the feasibility, acceptability, and tolerability of administering a single 6 mg oral dose of 17β-estradiol (E2) to individuals assigned female at birth who have experienced a sexual assault (SA) within the previous 120 hours. Thirty participants aged 18 to 45 years will be randomized 1:1 to receive either E2 or an identical-appearing placebo and followed for three months with blood collection and standardized assessments. The study will evaluate recruitment, enrollment, retention, biological responses, and preliminary clinical outcomes, including chronic musculoskeletal pain (CMSP) and posttraumatic stress disorder (PTSD), to inform the design of a future fully powered efficacy trial.
Read the detailed description
One in five U.S. females experience sexual assault in their lifetime, and CMSP and PTSD are common, costly, and difficult-to-treat outcomes. Despite the substantial public health burden of these conditions, few therapeutics exist to prevent CMSP or PTSD after SA. Preclinical and observational studies suggest that early administration of 17β-estradiol (E2) following traumatic stress may reduce the risk of developing CMSP and PTSD, with evidence indicating that the timing of E2 exposure relative to the traumatic event is critical. However, no randomized clinical trial has yet evaluated whether early E2 administration can prevent these outcomes following SA.
To address this gap, this pilot, randomized, double-blind, placebo-controlled trial will enroll 30 individuals assigned female at birth, aged 18 to 45 years, who experienced SA within the prior 120 hours. After screening and confirmation of eligibility, participants will be randomized 1:1 to receive either a single oral 6 mg dose of encapsulated E2 (three 2 mg tablets) or an identical placebo within 120 hours of the SA.
Blood samples will be collected immediately before study drug administration and again 90 to 120 minutes afterward to assess circulating E2, cortisol, inflammatory mediators (including IL-6, IL-8, IFN-γ, IL-10, and TNF-α), and RNA expression. Participants will complete standardized assessments of pain, PTSD symptoms, and related clinical outcomes at baseline and at Week 2, Week 6, and Month 3 following enrollment. The Month 3 visit will include a final blood collection.
The primary objectives of this pilot study are to evaluate the feasibility, acceptability, and tolerability of administering early E2 following SA. Secondary and exploratory objectives include characterizing the biological response to E2 administration and obtaining preliminary estimates of its effects on CMSP and PTSD symptoms. Findings from this study will inform the design and implementation of a future fully powered efficacy trial.
The selected E2 dose is based on observational findings demonstrating that peritraumatic circulating E2 concentrations above approximately 100 pg/mL are associated with a lower risk of CMSP and PTSD, together with the established safety profile of comparable oral E2 doses in other clinical settings.
- Being tested
- 17β-estradiol, Placebo
- Keywords
- 17β-estradiol, estradiol, estrogen, sexual assault, chronic musculoskeletal pain, chronic pain, trauma, traumatic stress, PTSD, posttraumatic stress disorder, secondary prevention, pain prevention, women's health
- Medical subject headings
- Stress Disorders, Post-Traumatic, Chronic Pain, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
17β-estradiolDrug
Single oral 6 mg dose micronized 17β-estradiol administered once.
PlaceboDrug
Single oral dose of matching placebo administered once.
| Study group | Role | What they receive |
|---|---|---|
| 17β-Estradiol (E2) | Experimental | Participants receive a single oral 6 mg dose of micronized 17β-estradiol (three encapsulated 2 mg tablets) administered within 120 hours of sexual assault. Receives: Drug: 17β-estradiol |
| Placebo | Placebo comparator | Participants receive a single oral dose of matching placebo administered within 120 hours of sexual assault. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Enrollment feasibility
Number and proportion of eligible individuals who complete the Screening Consent and are enrolled in the study.
Measured: Throughout the recruitment period, up to 18 months
Participant retention at Month 3
Proportion of enrolled participants who complete the Month 3 in-person visit, including final blood collection and study questionnaires. The prespecified retention target is at least 80%.
Measured: 3 months after study-drug administration
Acceptability of the study intervention
Participant-reported acceptability of the study intervention, assessed using items from the Medication Acceptability Questionnaire, including overall acceptability and willingness to recommend the intervention to others.
Measured: Enrollment Visit, following study drug administration, through Month 3
Tolerability of the study intervention
Number and proportion of participants reporting side effects or adverse events following study drug administration.
Measured: Study drug administration through Month 3
Secondary outcomes (6)
Plasma 17β-estradiol concentration
Change in plasma 17β-estradiol concentration from pre-dose to 90-120 minutes after study-drug administration, compared between treatment groups.
Measured: Pre-dose and 90-120 minutes post-dose
Plasma cortisol concentration
Change in plasma cortisol concentration from pre-dose to 90-120 minutes after study-drug administration and differences between treatment groups at Month 3.
Measured: Pre-dose, 90 to 120 minutes post-dose, and Month 3
Plasma inflammatory mediator concentrations
Changes in plasma concentrations of IL-6, IL-8, IFN-γ, IL-10 and TNF-α from pre-dose to 90-120 minutes after study-drug administration and differences between treatment groups at Month 3.
Measured: Pre-dose, 90 to 120 minutes post-dose, and Month 3
RNA expression
Changes in peripheral-blood RNA expression following study-drug administration, including differences in RNA expression profiles between treatment groups 90-120 minutes after study-drug administration and longitudinal changes from enrollment to Month-3.
Measured: Pre-dose, 90 to 120 minutes post-dose, and Month 3
Musculoskeletal pain severity
Pain severity measured using a 0 to 10 numeric rating scale, with higher scores indicating greater pain severity. Scores and changes from baseline will be compared between treatment groups.
Measured: Baseline, Week 2, Week 6, and Month 3
Posttraumatic stress disorder symptom severity (PCL-5)
Posttraumatic stress symptoms measured using the 20-item PTSD Checklist for DSM-5 (PCL-5). Total scores range from 0-80, with higher scores indicating greater symptom severity. Scores and changes from baseline will be compared between treatment groups.
Measured: Baseline, Week 2, Week 6, and Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2026
- Study start28 Sep 2026 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Musculoskeletal PainStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm 1: Single oral 6 mg dose of 17β-estradiol (E2) administered within 120 hours of sexual assault Arm 2: Single oral dose of matching placebo administration within 120 hours of sexual assault
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sarah Linnstaedt, PhD, University of North Carolina, Chapel Hill
- Investigators
- Sarah Linnstaedt, PhD, Principal investigator, University of North Carolina, Chapel HillJennifer Tang, MD, MSCR, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07868536
- Sponsor's protocol ID
- 24-2724
- Acronym
- PEACE
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2026
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) underlying the results reported in published manuscripts may be shared after publication of the primary study findings. All shared data will be de-identified in accordance with applicable federal regulations and institutional policies.
Publications
Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239.
PubMed 27777223Ferree NK, Wheeler M, Cahill L. The influence of emergency contraception on post-traumatic stress symptoms following sexual assault. J Forensic Nurs. 2012 Sep;8(3):122-30. doi: 10.1111/j.1939-3938.2012.01134.x. Epub 2012 Mar 5.
PubMed 22925127Linnstaedt SD, Mauck MC, Son EY, Tungate AS, Pan Y, Rueckeis C, Yu S, Lechner M, Datner E, Cairns BA, Danza T, Velilla MA, Pearson C, Shupp JW, Smith DJ, McLean SA. Peritraumatic 17beta-estradiol levels influence chronic posttraumatic pain outcomes. Pain. 2021 Dec 1;162(12):2909-2916. doi: 10.1097/j.pain.0000000000002282.
PubMed 34028234Son E, Gaither R, Lobo J, Zhao Y, McKibben LA, Arora R, Albertorio-Saez L, Mickelson J, Wanstrath BJ, Bhatia S, Stevens JS, Jovanovic T, Koenen K, Kessler R, Ressler K, Beaudoin FL, McLean SA, Linnstaedt SD. Further evidence that peritraumatic 17beta-estradiol levels influence chronic posttraumatic pain outcomes in women, data from both humans and animals. Pain. 2025 Apr 1;166(4):812-823. doi: 10.1097/j.pain.0000000000003408. Epub 2024 Sep 13.
PubMed 39287098