Depression - Major Depressive DisorderPhase 4TeenVIBENCT07544966
Teen Vulnerability to Irritability: Brain and Estrogen Changes
A Phase 4 study testing Kurvelo in people with Depression - Major Depressive Disorder and Irritability, run by University of North Carolina, Chapel Hill at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 to 16 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Depression - Major Depressive Disorder, Irritability
- What is being tested?
- Kurvelo
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2026to Apr 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 12 to 16 years
- Women only
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Natalie Deeb contact
United States2 sites
Biomedical Research Imaging Center (BRIC) at UNC
Chapel Hill, North Carolina, 27517
Carolina Crossing
Chapel Hill, North Carolina, 27517
Elizabeth Andersen, PhD, (919) 843-8084, Elizabeth_Andersen@med.unc.edu
Peyton Miyares, peyton_miyares@med.unc.edu
About this study
Official title: Neurobiological Mechanisms of Susceptibility to Estradiol Fluctuation in Female Adolescents at Risk of Suicide: An Experimental Approach
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).
- Being tested
- Kurvelo, Placebo COC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KurveloDrug
Kurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively.
Placebo COCDrug
Placebo pills from the Kurvelo® packages (cut from package to maintain blinding).
| Study group | Role | What they receive |
|---|---|---|
| Kurvelo®, then Placebo COC | Active comparator | 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. Receives: Drug: Kurvelo; Drug: Placebo COC |
| Placebo COC, then Kurvelo® | Placebo comparator | 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). Receives: Drug: Kurvelo; Drug: Placebo COC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Irritability Symptoms (average Brief Irritability Test (BITe) across each 8-week condition)
The Brief Irritability Test (BITe) is a 5-item self-report instrument developed to measure irritability as a distinct emotional construct, defined by increased susceptibility to frustration, annoyance, and anger in response to minimal provocation. Participants rate each item (e.g., feeling grumpy, easily annoyed, on edge) using a 6-point Likert scale ranging from Never (1) to Always (6). Total scores range from 5 to 30, with higher scores indicating greater irritability. BITe total score is calculated as the sum of the five items.
Measured: Average Brief Irritability Test (BITe) will be collected daily across the complete study duration (week 1 -24).
Secondary outcomes (3)
Irritable behavior (point subtraction aggression paradigm (PSAP)
The Point Subtraction Aggression Paradigm (PSAP) is a computerized task measuring reactive aggression in response to provocation. Participants believe they compete with an opponent to earn points. They may earn points, subtract a point from the opponent (aggressive response), or activate protection. Aggression is quantified as the number of point-subtraction responses, with higher values indicating greater aggressive behavior. Scores range from 0 to the total number of opportunities/response trials within the task session, depending on task duration and provocation frequency.
Measured: 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
Scanning will be conducted using a 7 Tesla Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32-channel receive array head coil to obtain high-quality spectra from the medial prefrontal cortex (mPFCpref, 20 × 20 × 20 mm). The MRS voxels processed within the mPFC will be passed to the metabolite quantification process to quantify the level of gamma-aminobutyric acid (GABA).
Measured: 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).
Connectivity strength (-1 to +1) between the amygdala and frontal network (medial, ventrolateral, ventromedial prefrontal cortex).
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study start1 Oct 2026 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression - Major Depressive DisorderStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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 hormone 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 STBs) 3. a neuroimaging session.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Responsible party
- Sponsor
- Investigators
- Elizabeth Andersen, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07544966
- Sponsor's protocol ID
- 25-2243
- Acronym
- TeenVIBE
- Status last verified
- Aug 2026
- First submitted
- 2 Feb 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Mechanisms of Susceptibility to Estradiol Fluctuation in Female Adolescents at Risk of Suicide: An Experimental Approach
- ClinicalTrials.gov ID
- NCT07544966
- Acronym / sponsor ID
- TeenVIBE / 25-2243
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2029 (estimated)
- First posted
- 22 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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 hormone 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 STBs) 3. a neuroimaging session.
| Arm | Type | Receives |
|---|---|---|
| Kurvelo®, then Placebo COC | Active comparator | Drug: Kurvelo, Drug: Placebo COCParticipants 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 COC, then Kurvelo® | Placebo comparator | Drug: Kurvelo, Drug: Placebo COCParticipants 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). |
Who may qualify
- Ages
- 12 to 16 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- Personal history of metabolic or autoimmune disease
- Epilepsy
- Endometriosis
- Cardiovascular, gastrointestinal, hepatic, renal, or pulmonary disease Diabetes mellitus with vascular disease
- Uncontrolled hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KurveloKurvelo®: 30mcg ethinyl estradiol (EE) and 0.15mg levonorgestrel (LNG), a synthetic estrogen and progestin, respectively. | Drug | Kurvelo®, then Placebo COC, Placebo COC, then Kurvelo® |
| Placebo COCPlacebo pills from the Kurvelo® packages (cut from package to maintain blinding). | Drug | Kurvelo®, then Placebo COC, Placebo COC, then Kurvelo® |
Primary outcome
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).
The Brief Irritability Test (BITe) is a 5-item self-report instrument developed to measure irritability as a distinct emotional construct, defined by increased susceptibility to frustration, annoyance, and anger in response to minimal provocation. Participants rate each item (e.g., feeling grumpy, easily annoyed, on edge) using a 6-point Likert scale ranging from Never (1) to Always (6). Total scores range from 5 to 30, with higher scores indicating greater irritability. BITe total score is calculated as the sum of the five items.
3 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Natalie Deeb contact
Elizabeth Andersen, PhD principal investigator
University of North Carolina, Chapel Hill
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Kurvelo in people with Depression - Major Depressive Disorder and Irritability, run by University of North Carolina, Chapel Hill at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elizabeth Andersen, PhD ((919) 843-8084, Elizabeth_Andersen@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.