Neurobiological Mechanisms of Pathological Rumination and Effects of Aripiprazole (NCT06937476) | Clinical Trial Compass
Active — Not RecruitingNot Applicable
Neurobiological Mechanisms of Pathological Rumination and Effects of Aripiprazole
China108 participantsStarted 2025-05-08
Plain-language 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. Clinical assessments will be repeated during the 8-week treatment phase, including interim monitoring visits for efficacy and safety. The primary clinical endpoint is the change in Ruminative Responses Scale (RRS) scores from baseline to week 8.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 and again at week 10, after tapering and discontinuation of aripiprazole during weeks 9-10, 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
Age range
18 Years – 45 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
For Patients With Major Depressive Disorder (MDD):
* Age 18 to 45 years
* Any sex
* Self-identified Han Chinese
* Right-handed
* Education level of junior high school or above
* Able to understand the informed consent form and complete self-report assessments
* Meets DSM-5 diagnostic criteria for Major Depressive Disorder (MDD) based on the Structured Clinical Interview for DSM-5 (SCID)
* Currently experiencing a major depressive episode
* 24-item Hamilton Depression Rating Scale (HAMD-24) score \>= 21 at screening/baseline
* Young Mania Rating Scale (YMRS) score \<= 5 at screening/baseline
* No psychotropic medication use, other than benzodiazepines, within 6 weeks before baseline
Pathological Rumination Group:
* Must meet all of the following criteria:
* Subjective experience of persistent and difficult-to-control ruminative thinking
* Interview-confirmed pathological rumination characterized by all of the following features:
* Repetitive
* Intrusive
* Difficult to disengage from
* Unproductive
* Occupying substantial mental resources
* Ruminative Responses Scale (RRS) score \>= 61
Low Rumination Group:
* Does not meet criteria for the Pathological Rumination Group
* Ruminative Responses Scale (RRS) score \< 61
For Healthy Controls:
* Age 18 to 45 years
* Any sex
* Self-identified Han Chinese
* Right-handed
* Education level of junior high school or above
* Able to understand the informed consent form and complete self-report assessments
* Does n…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is specifically studying rumination as a feature of depression, and I do struggle a lot with repetitive negative thinking — is rumination actually a significant part of my depression diagnosis, and does that make this trial more relevant to my situation?
2The trial uses aripiprazole, which I know is sometimes used as an add-on medication for depression — can you explain what role aripiprazole is playing in this study, and whether it would be used alongside any antidepressant I'm already taking or might start?
3The trial is no longer actively recruiting new participants — does that mean there's no chance of enrolling, or is it worth asking the research team directly whether any spots have opened up?
4Since this is listed as Phase NA rather than a standard Phase 1, 2, or 3 trial, what does that mean for how much is already known about the safety and effectiveness of this approach, and how does that uncertainty compare to standard depression treatments I could try instead?
5The main thing being measured is change in rumination scores over 8 weeks — if I were to discuss this with the research team, what would the commitment look like in terms of visits, tests, or time away from work or home?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Change in Ruminative Responses Scale (RRS) score from baseline to week 8