Teen Vulnerability to Irritability: Brain and Estrogen Changes

Part of paid clinical trials in Chapel Hill, North Carolina.

Sponsor
University of North Carolina, Chapel Hill
Study ID
NCT07544966
Phase
PHASE4
Status
Not Yet Recruiting

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Conditions

  • Depression - Major Depressive Disorder
  • Irritability

Eligibility Criteria

Sex
FEMALE
Age
12 Years - 16 Years
Healthy Volunteers
Accepted

Interventions

  • Kurvelo — DRUG
    Kurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively.
  • Placebo COC — DRUG
    Placebo pills from the Kurvelo® packages (cut from package to maintain blinding).

Study Details

Purpose: Risk of severe psychopathology increases dramatically during adolescence, especially for females. Changes in ovarian steroids across the menstrual cycle produce windows of vulnerability to mood disturbances, particularly during the abrupt withdrawal of estradiol (E2) and progesterone (P4) prior to menses onset. Irrefutable evidence links stress with affective symptoms, potentially mediated by E2-related modifications of frontolimbic connectivity and prefrontal gamma-aminobutyric acid (GABA) inhibitory signaling. The primary objective of this project is to empirically test the impact of E2 and P4 change on vulnerable brain networks associated with irritability and other depressive symptoms in female adolescents at risk of suicide. Participants: The investigators will enroll 50 female adolescents ages 12-16 who are at risk of suicide (i.e., moderate depressive symptoms), and are eligible to receive oral contraceptives and undergo MRI imaging. Procedure: Using a randomized, placebo-controlled, cross-over design, participants will be studied under two conditions: 8 weeks of E2 and P4 stabilization (continuous combined oral contraceptive (COC) to prevent perimenstrual withdrawal) and 8 weeks of placebo, with a 1-month washout after each condition. Each condition will include: 1) daily samples of E2 and P4 urinary metabolites, 2) daily symptom ratings(e.g., irritability, negative affect and suicidal thoughts and behaviors (STBs)), and 3) a neuroimaging session with MRI and magnetic resonance spectroscopy (MRS).

Key Dates

Start date
Jun 1, 2026
Status verified
Apr 2026
Primary completion
Apr 30, 2028
Completion
Apr 30, 2029

Study Design

Enrollment
50 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Active Comparator: Kurvelo®, then Placebo COC
    Participants will receive 8-weeks of continuous combined oral contraceptive (COC; Kurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively). A 4-week washout period will then occur after which participants will receive 8-weeks of continuous placebo combined oral contraceptive (COC) pills.
  • Placebo Comparator: Placebo COC, then Kurvelo®
    Participants will receive 8-weeks of continuous placebo combined oral contraceptive (COC) pills. A 4-week washout period will then occur after which participants will receive 8-weeks of continuous combined oral contraceptive (COC; Kurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively).

Primary Outcome Measure

Irritability Symptoms (average Brief Irritability Test (BITe) across each 8-week condition) [ Time Frame: Average Brief Irritability Test (BITe) will be collected daily across the complete study duration (week 1 -24). ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Biomedical Research Imaging Center (BRIC) at UNCChapel HillNorth Carolina27517-
Carolina CrossingChapel HillNorth Carolina27517
Elizabeth Andersen, PhD
[email protected]
919-843-8084
Peyton Miyares
[email protected]

Find similar trials in Chapel Hill, NC

By research site
Biomedical Research Imaging Center (BRIC) at UNC· Chapel Hill, NCCarolina Crossing· Chapel Hill, NC

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