Teen Vulnerability to Irritability: Brain and Estrogen Changes
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Kurvelo, Placebo COC.
- Who it may be relevant to
- Registry conditions: Depression - Major Depressive Disorder, Irritability. Basic parameters: 12 years — 16 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Neurobiological Mechanisms of Susceptibility to Estradiol Fluctuation in Female Adolescents at Risk of Suicide: An Experimental Approach.
Overview
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).
Interventions
- Drug Kurvelo
Kurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively. - Drug Placebo COC
Placebo pills from the Kurvelo® packages (cut from package to maintain blinding).
Primary outcome measures
- 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).]
Secondary outcome measures (3)
- Irritable behavior (point subtraction aggression paradigm (PSAP) [Time frame: During the neuroimaging session (inside the scanner) at week 8 (1 time point during the last week of condition 1) and week 20 (1 time point during the last week of condition 2)]
- medial prefrontal cortex GABAergic activity [Time frame: During the neuroimaging session (inside the scanner) at week 8 (1 time point during the last week of condition 1) and week 20 (1 time point during the last week of condition 2)]
- Functional connectivity between amygdala and frontal network (medial, ventrolateral, ventromedial prefrontal cortex). [Time frame: During the neuroimaging session (inside the scanner) at week 8 (1 time point during the last week of condition 1) and week 20 (1 time point during the last week of condition 2)]
Eligibility criteria
Inclusion criteria
- Assigned female sex at birth
- Between the ages of 12 and 16
- Be eligible to receive a low-dose oral contraceptive (COC)
- Post-menarche. Participants will be post-menarche to avoid potential OC-related effects on bone growth prior to menarche
- At risk of suicide. To be considered "at suicide risk" participants must meet the following-Mood and Feelings Questionnaire score of ≥ 27
Exclusion criteria
- Personal history of metabolic or autoimmune disease
- Epilepsy
- Endometriosis
- Cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease Diabetes mellitus with vascular disease
- Uncontrolled hypertension
- Liver tumors (benign or malignant) or liver disease
- Undiagnosed abnormal uterine bleeding
- Headaches with focal neurological symptoms or migraine with aura
- Known or suspected pregnancy
- Current or past deep vein thrombosis or pulmonary embolism
- Cerebrovascular disease Coronary artery disease
- Thrombogenic valvular or rhythm disease (e.g., subacute bacterial endocarditis with valvular disease, atrial fibrillation)
- Inherited or acquired hypercoagulopathies
- Current or history of breast cancer or other hormone-sensitive malignancy
- Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
- Personal or first-degree relative with breast cancer or thromboembolic events
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Double blind
- Primary purpose
- Basic science
Study locations
United States · 2 centers
- Biomedical Research Imaging Center (BRIC) at UNC — Chapel Hill
- Carolina Crossing — Chapel Hill
Identifiers
NCT: NCT07544966 · 25-2243