Investigation of the Neurobiological Mechanisms Underlying Pathological Rumination and the Pharmacological Effects of Aripiprazole
Trial tests if aripiprazole helps reduce repetitive negative thinking in depression.
Plain English Summary
Neurobiological Mechanisms of Pathological Rumination and Effects of Aripiprazole is a Not Applicable clinical trial sponsored by Central South University studying Major Depressive Disorder (MDD), Rumination. This study investigates if adding aripiprazole to a common antidepressant (escitalopram) can help people with major depression who get stuck in negative thought patterns (rumination). It is for adults aged 18-45 who have been diagnosed with major depressive disorder and experience significant rumination. Participants will take either escitalopram alone or escitalopram plus aripiprazole for 8 weeks, and undergo brain scans (PET-MRI) at the start and end of the study. Standard treatment for depression with escitalopram is the alternative if aripiprazole is not chosen or suitable. The trial aims to enroll 108 participants.
Official Summary
This randomized, single-blind (assessor-blind) controlled trial aims to investigate the efficacy of aripiprazole as an augmentation strategy for treating pathological rumination in patients with major depressive disorder (MDD). Pathological rumination-defined as repetitive, intrusive, and uncontrollable negative thinking-has been identified as a major transdiagnostic risk factor for the development, maintenance, and recurrence of depression. Even during clinical remission, ruminative symptoms often persist and strongly predict relapse. Previous clinical observations and experimental studies suggest that aripiprazole, a partial dopamine D2 receptor agonist, can significantly improve cognitive symptoms and reduce rumination in MDD patients when added to selective serotonin reuptake inhibitors (SSRIs). However, rigorous randomized controlled trials (RCTs) directly targeting rumination and validating this effect remain limited. In this study, patients with acute MDD episodes and high levels of rumination will be randomly assigned to receive either escitalopram monotherapy (20 mg/day) or escitalopram (20 mg/day) plus low-dose aripiprazole (2.5-5 mg/day) for 8 weeks. The assignment will remain blinded to outcome assessors and data analysts, while patients and treating clinicians will remain unblinded due to dose titration and safety monitoring requirements. Participants will undergo \[18F\]fallypride-PET-MRI scanning at baseline and post-treatment to measure striatal dopamine D2 receptor binding and explore its association with changes in rumination symptoms and treatment efficacy. The primary outcome is the change in Ruminative Responses Scale (RRS) scores. Secondary outcomes include changes in depressive symptoms and dopamine D2 receptor availability. This trial will provide neurobiological insights into the dopaminergic mechanisms underlying pathological rumination and explore the therapeutic potential of D2 receptor modulation in this cognitive domain.
Who Can Participate
Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 45 years old, have major depression, and experience a lot of repetitive negative thinking. You cannot join if you have other major psychiatric disorders (besides anxiety), severe suicidal thoughts, a history of brain injury, serious medical conditions, or implants that are not MRI/PET compatible. You must not have taken psychiatric medications (except for certain anxiety medications) in the past 6 weeks and cannot have had certain brain treatments in the last 6 months. Participants must be of Han Chinese ethnicity and right-handed, with at least a junior high school education. This trial is studying Major Depressive Disorder (MDD), Rumination, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.
What They're Measuring
The main goal is to see if a specific score measuring how much people get stuck in negative thinking decreases after 8 weeks of treatment. The specific primary outcome measures are: Change in Ruminative Responses Scale (RRS) score from baseline to week 8 (Baseline and week 8). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.
Why This Trial Matters
This trial addresses a significant gap in treating depression by exploring a new way to manage persistent, intrusive negative thoughts that often lead to relapse, even when other depression symptoms i This research targets Major Depressive Disorder (MDD), Rumination, where improved treatment options are needed.
Investor Insight
This trial could signal a new treatment approach for a common and persistent symptom of depression, potentially expanding the market for aripiprazole and offering a new therapeutic option if successfu
Is This Trial Right for Me?
Ask your doctor if this trial is right for you, especially how it differs from standard depression treatment. You will need to attend regular appointments for medication, assessments, and brain scans. The study involves taking prescribed medications daily and potentially experiencing side effects from them. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: PARALLEL
- Masking: SINGLE
- Enrollment: 108 participants
Interventions
- DRUG: Escitalopram — Escitalopram will be administered orally at a fixed dose of 20 mg/day for 8 weeks. This SSRI antidepressant is used as baseline pharmacological treatment for patients with major depressive disorder (MDD), either as monotherapy or in combination with aripiprazole. No other psychotropic medications are allowed during the study period.
- DRUG: Aripiprazole 5mg — Aripiprazole will be administered as an adjunctive treatment to escitalopram at an initial dose of 2.5 mg/day, titrated up to 5 mg/day based on tolerability. Treatment will last 8 weeks, after which aripiprazole will be tapered and discontinued. This intervention aims to evaluate the efficacy of dopaminergic augmentation in reducing pathological rumination symptoms.
Primary Outcomes
- Change in Ruminative Responses Scale (RRS) score from baseline to week 8 (Baseline and week 8)
Secondary Outcomes
- Change in 24-item Hamilton Depression Rating Scale (HAMD-24) score (Baseline and week 8)
Full Eligibility Criteria
Inclusion Criteria: * For Patients with Major Depressive Disorder (MDD): Age 18 to 45 years old, any sex. Han Chinese, right-handed. Education level of junior high school or above, able to understand informed consent and complete self-report instruments. Meets DSM-5 diagnostic criteria for Major Depressive Disorder (MDD) based on the SCID interview. Currently experiencing a depressive episode: HAMD-24 score ≥ 21 YMRS score ≤ 5 No psychotropic medication (except benzodiazepines) in the past 6 weeks. Classified into one of two cognitive subgroups based on rumination: Pathological Rumination Group: Must meet all three of the following: 1. Subjective experience (e.g., "I can't stop thinking about past regrets" or "I can't control painful thoughts...") 2. Interview-confirmed features of pathological rumination (all of the following): Repetitive Intrusive Difficult to disengage Unproductive Capturing mental capacity 3. Ruminative Responses Scale (RRS) score ≥ 61 Low Rumination Group: Does not meet the above criteria. Exclusion Criteria: * Meets DSM-5 criteria for psychiatric disorders other than anxiety disorders. MDD with psychotic features. Severe suicidal ideation or behavior. History of traumatic brain injury or loss of consciousness. Serious neurological or medical illness (e.g., thyroid disorders, lupus, diabetes, infection, trauma). Cardiac pacemaker or any metallic implants incompatible with MRI/PET. History of alcohol or substance dependence. Pregnant or breastfeeding. Personal or family history of epilepsy. Underwent non-pharmacological psychiatric interventions (e.g., ECT, rTMS, psychotherapy) in the past 6 months.
Trial Locations
- The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Frequently Asked Questions
What is clinical trial NCT06937476?
NCT06937476 is a Not Applicable INTERVENTIONAL study titled "Neurobiological Mechanisms of Pathological Rumination and Effects of Aripiprazole." It is currently recruiting and is sponsored by Central South University. The trial targets enrollment of 108 participants.
What conditions does NCT06937476 study?
This trial investigates treatments for Major Depressive Disorder (MDD), Rumination. The primary condition under study is Major Depressive Disorder (MDD).
What treatments are being tested in NCT06937476?
The interventions being studied include: Escitalopram (DRUG), Aripiprazole 5mg (DRUG). Escitalopram will be administered orally at a fixed dose of 20 mg/day for 8 weeks. This SSRI antidepressant is used as baseline pharmacological treatment for patients with major depressive disorder (MDD), either as monotherapy or in combination with aripiprazole. No other psychotropic medications are allowed during the study period.
What does Not Applicable mean for NCT06937476?
This study does not have a defined clinical phase. It may be an observational study, expanded access program, or other non-interventional research.
What is the current status of NCT06937476?
This trial is currently "Recruiting." It started on 2025-05-08. The estimated completion date is 2026-03.
Who is sponsoring NCT06937476?
NCT06937476 is sponsored by Central South University. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT06937476?
The trial aims to enroll 108 participants. The trial is currently recruiting and accepting new participants.
How is NCT06937476 designed?
This is a interventional study, uses randomized allocation, follows a parallel design, employs single masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.
What are the primary outcomes being measured in NCT06937476?
The primary outcome measures are: Change in Ruminative Responses Scale (RRS) score from baseline to week 8 (Baseline and week 8). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT06937476 being conducted?
This trial is being conducted at 1 site, including Changsha, Hunan (China).
Where can I find official information about NCT06937476?
The official record for NCT06937476 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06937476. This government database provides the most up-to-date and detailed information about the trial.
What is NCT06937476 testing in simple terms?
This study investigates if adding aripiprazole to a common antidepressant (escitalopram) can help people with major depression who get stuck in negative thought patterns (rumination). It is for adults aged 18-45 who have been diagnosed with major depressive disorder and experience significant rumination.
Why is this trial significant?
This trial addresses a significant gap in treating depression by exploring a new way to manage persistent, intrusive negative thoughts that often lead to relapse, even when other depression symptoms i
What are the potential risks of participating in NCT06937476?
Common side effects of escitalopram can include nausea, insomnia, and sexual dysfunction. Aripiprazole can cause side effects like restlessness, weight gain, and sometimes movement problems. Brain scans involve radiation exposure, although the dose is carefully controlled. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT06937476?
Ask your doctor if this trial is right for you, especially how it differs from standard depression treatment. You will need to attend regular appointments for medication, assessments, and brain scans. The study involves taking prescribed medications daily and potentially experiencing side effects from them. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT06937476 signal from an investment perspective?
This trial could signal a new treatment approach for a common and persistent symptom of depression, potentially expanding the market for aripiprazole and offering a new therapeutic option if successfu This is a Not Applicable trial, which is in early development stages.
What happens if the treatment in this trial doesn't work?
Participants will take either escitalopram alone or escitalopram plus aripiprazole for 8 weeks, and undergo brain scans (PET-MRI) at the start and end of the study. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
Related Conditions
- Major Depressive Disorder
- Rumination
- Depression Relapse
- Cognitive Symptoms of Depression
- Anxiety Disorders
- Obsessive-Compulsive Disorder (related to repetitive thoughts)
- Bipolar Disorder (as a differential diagnosis)
- Schizophrenia (as a differential diagnosis)
- Dopamine Receptor Agonists
- Selective Serotonin Reuptake Inhibitors (SSRIs)
More Major Depressive Disorder (MDD) Trials
This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.