Unipolar DepressionPhase 4NCT07266545
RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)
A Phase 4 study testing Vortioxetine and Cariprazine (Augmentation Phase) in people with Unipolar Depression and Bipolar Depression, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Unipolar Depression, Bipolar Depression
- What is being tested?
- Vortioxetine and Cariprazine (Augmentation Phase)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2026to 31 Dec 2030
- Phase
- Phase 4
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all the following criteria to be eligible for the study:
- Adult females and males, aged 18-65 years
- Must have the capacity to understand study procedures, to comply with them for the entire length of the study, and to provide informed consent.
- Current major depressive episodes associated with MDD, BD-I, or BD-II, confirmed using the SCID-IV-CV. If a participant has already completed a structured diagnostic interview within the last 2 years or participated in any of the following studies and provided consent to use their information in future studies: (IRB 19-001722, IRB: 23-004500, IRB: 24-013228, IRB: 25-005856, IRB: 25-007244), those SCID results can be used for the EDIT-ANDRE study.
- Symptom severity score on the Quick Inventory for Depressive Symptomatology - Clinician (QIDS-C16) > 10.
- Ability to travel for assessment visits.
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- Negative urine pregnancy test for people of childbearing potential
- People of childbearing potential must be using an acceptable method of birth control during the study, such as hormonal contraception, intrauterine device, bilateral tubal ligation, partner's documented vasectomy, or complete abstinence from intercourse with childbearing potential, with barrier methods permitted only when used in combination with one of these primary methods.
- BD-I patients must be on stable dose of at least one mood stabilizer (i.e., lithium, valproate, or a mood-stabilizing atypical antipsychotic at least for one month) at the time of enrollment.
- Patients with BD-II who enroll in the study while currently taking a mood stabilizer (including lithium, valproate, or lamotrigine) must have been on a stable dose of that medication for a minimum of one month before enrollment.
Who cannot join
- All candidates meeting any of the following criteria at baseline will be excluded from study participation:
- Individuals who cannot understand English will not be enrolled because informed consent, study procedures, and interviews require comprehension of English.
- Inability to provide written, voluntary informed consent due to but not limited to being under conservatorship, guardianship, commitment, or currently undergoing involuntary psychiatric hospitalization.
- Failure to score at least 75% on a 4-item comprehension assessment related to study goals, risks, and benefits
- For BD-I: not having used at least one mood stabilizer (e.g., lithium, valproate, or mood-stabilizing antipsychotics) at a stable dose and within a therapeutically effective antimanic range for a minimum of one month.
- History of treatment-refractory depression, defined as non-response to two or more antidepressant or mood-stabilizing regimens despite adequate dose, duration, and adherence during the current episode.
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- Participants with active suicidal ideation, defined as a MADRS item #10 score greater than 4 or a "yes" response to item #4 (ideation with intent) or item #5 (ideation with plan) on the C-SSRS, will be excluded
- A medically serious suicide attempt within the past 6 months, defined as requiring emergency department evaluation, a medical procedure, or admission to a hospital (e.g., internal medicine, cardiology, or ICU)
- Current use of monoamine oxidase inhibitors or use within 14 days following discontinuation of a monoamine oxidase inhibitor
- Presence of mixed symptoms of depression, defined as a YMRS score ≥12
- Current use of any of the study medications (e.g., vortioxetine, or cariprazine) at the time of enrollment (previous use of these medications is acceptable)
- Prior hypersensitivity reaction to any of the study medications or documented non-response to any of the study medications at the maximum therapeutic dose
- A history of seizure disorder
- Recent use of long half-life psychotropic medications, including fluoxetine (in patients with BD and MDD) and long acting injectable forms of antipsychotics (mainly in BD II and MDD) within the past 4 weeks.
- Active psychosis, defined as a YMRS item #8 score >4 or diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or schizophreniform disorder as determined by structured clinical interview
- Current drug or alcohol use disorder (excluding nicotine); full remission for at least 3 months is required for eligibility
- Positive toxicology screen for illicit substances (e.g., cocaine, methamphetamine, illegal opiates). Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included in the study only if they take the CUDIT-R and score a 12 or less.
- Individuals who are pregnant, lactating, trying to conceive, or not using adequate contraception (e.g., hormonal contraception, intrauterine device, tubal ligation, or condoms)
- Any active or unstable medical condition judged by the principal investigator to confer excessive risk
- Clinically significant laboratory abnormality, uncontrolled hypertension (blood pressure >160/100 mmHg), or tachycardia (heart rate >110 bpm)
- Significant renal, hepatic, or cardiac disease; malignancy; autoimmune disease; or chronic kidney disease > stage IIIa (estimated GFR < 60 mL/min/1.73 m²)
- History of traumatic brain injury defined as loss of consciousness for 5 minutes and related to a trauma event
- Gastric bypass, specifically Roux-en-Y
- Clinical current diagnosis of delirium, encephalopathy, intellectual disability or cognitive disorder (mild or major neurocognitive disorder)
- Currently receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), or deep brain stimulation (DBS) as acute or maintenance treatment
- Current use of systemic steroids, chemotherapy, and radiotherapy
- Daily use of lorazepam (Ativan) >4 mg/day, or equivalent doses of other benzodiazepines (e.g., clonazepam >1 mg, alprazolam >2 mg, diazepam >20 mg)
- No access to smartphones, internet
- Other Axis I or II diagnoses, by clinical judgments that are the current reason for treatment evaluation or play a large part of the current symptom presentation
- Ongoing treatment with opioid agonists will constitute an exclusion criterion. In contrast, other ongoing treatments, such as alcohol relapse prevention agents or ADHD pharmacotherapy, will not be considered exclusion criteria, provided that no treatment initiation or significant dose adjustment has occurred within the past 4 weeks.
- All candidates meeting any of the following criteria at baseline will be excluded from the Phase 2 (cariprazine add-on) of the study:
- Meeting symptomatic remission criteria based on MADRS (≤ 10).
- Current use of a strong or moderate CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, fluconazole, or verapamil) strong or moderate CYP3A4 inducer (e.g., carbamazepine, rifampin, phenytoin, or St. John's Wort), due to potential pharmacokinetic interactions with cariprazine.
- Diagnosis of BD-I with concurrent use of an antipsychotic agent as a mood stabilizer.
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, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Scott E. Feeder, 507-255-1975
Aysegul Ozerdem, MD, PhD
About this study
The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.
- Conditions
- Unipolar Depression, Bipolar Depression
- Being tested
- Vortioxetine, Cariprazine (Augmentation Phase)
- Medical subject headings
- Depressive Disorder, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VortioxetineDrug
Vortioxetine, once daily, for 8 weeks
Cariprazine (Augmentation Phase)Drug
Participants who do not meet remission criteria will enter a second 8-week augmentation phase (Weeks 9-16).
During this phase, cariprazine will be added to the existing regimen, administered orally once daily in the morning, starting at 1.5 mg/day and titrated up to 3.0 mg/day in one week.
| Study group | Role | What they receive |
|---|---|---|
| Vortioxetine | Experimental | Subjects will be started on vortioxetine for 8 weeks of treatment with vortioxetine at 10 mg/day, titrated to 20 mg/day (after 7 days).
Subjects who do not meet remission criteria will enter a second 8 week augmentation phase. Receives: Drug: Vortioxetine; Drug: Cariprazine (Augmentation Phase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score
The Montgomery-Åsberg Depression Rating Scale (MADRS) is scored on a scale of 0 to 60, with each of the 10 items rated from 0 to 6 by a trained clinician during an interview. A higher score indicates a more severe level of depression, with common severity ranges being: 0-6 (normal), 7-19 (mild), 20-34 (moderate), and 35-60 (severe).
Measured: Baseline, Week 2, Week 8, Week 10, Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
17 Feb 202631 Dec 2030
- First posted5 Dec 2025
- Study start17 Feb 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unipolar DepressionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aysegul Ozerdem, Mayo Clinic
- Investigators
- Aysegul Ozerdem, MD, PhD, Principal investigator, Mayo ClinicDeniz Ceylan, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07266545
- Sponsor's protocol ID
- 25-006875
- Status last verified
- Feb 2026
- First submitted
- 25 Nov 2025
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No