Dopaminergic Dysfunction in Late-Life Depression (NCT04469959) | Clinical Trial Compass
CompletedPhase 2
Dopaminergic Dysfunction in Late-Life Depression
United States79 participantsStarted 2021-02-15
Plain-language summary
Late-Life Depression (LLD), or depression in older adults, often presents with motivational deficits, deficits in performance in cognitive domains including processing speed and executive dysfunction, and mobility impairments. This triad of findings implicate dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute to cognitive decline and motor disability. Normal aging results in brain-wide dopamine declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain changes associated with depression and aging converge on dopamine circuits, the specific disturbances in LLD and how responsive the system is to modulation remain unclear. In this study, investigators are testing integrative model that aging, in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes affects behaviors supported by these circuits, in the context of age-associated cortical atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes. Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders contributes to slowed processing speed and mobility impairments that increase the effort cost associated with voluntary behavior. The central hypothesis of this study is that late-life depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine functioning in the brain. By improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms.
Who can participate
Age range
60 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
. Age ≥ 60 years
. Diagnostic and Statistical Manual-5 (DSM5) diagnosis of Major Depressive Disorder, Persistent Depressive Disorder, or Depression Not Otherwise Specified (NOS)
. MADRS score ≥ 15
. Decreased processing speed (0.5 SD below age-adjusted norms on the WAIS-IV Coding task or Trail Making Test, Part A) or decreased motor speed (gait speed/average walking speed on 15' course ≤ 1m/s, or 0.5 SD below age-, gender- and education-adjusted norms on the grooved pegboard test)
. Capable of providing informed consent and adhering to study procedures
Exclusion criteria
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 looked at how levodopa — a Parkinson's drug — might affect depression, thinking speed, and gait in older adults; given that it's now completed, has any data been published yet, and could the results change how you might approach my treatment?
2The trial measured things like processing speed tests and a 'willingness to work for rewards' task, which suggests dopamine problems may be driving both my mood and my motivation — do you think that kind of dopaminergic dysfunction could be part of what's happening with me specifically?
3Since this was a Phase 2 trial that's now finished, what does that mean for how confident we should be in the safety and effectiveness of using something like levodopa for late-life depression, versus sticking with standard antidepressants?
4The study included people with treatment-resistant depression alongside gait impairment and cognitive decline — if I have some of those features too, does that make me a candidate to discuss dopamine-focused treatments with you, or is that still too experimental?
5Are there any follow-up trials or approved treatment pathways being developed based on what this study was exploring, so we could consider those options if standard treatments aren't working well enough for me?
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 WAIS-R Digit Symbol Task Score
Timeframe: Baseline, after week 3, and after week 6
2
Change in Pattern Comparison Test Score
Timeframe: Baseline, after week 3, and after week 6
3
Change in Letter Comparison Test Score
Timeframe: Baseline, after week 3, and after week 6
4
Change in NIH EXAMINER Test Score
Timeframe: Baseline, after week 3, and after week 6
5
Change in Gait pattern
Timeframe: Baseline, after week 3, and after week 6
6
Change in Effort Expenditure for Rewards Task (EEfRT)
. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) in the past 12 months
. Other psychiatric disorders including a history of psychosis, psychotic disorder, mania, or bipolar disorder. Other comorbid psychiatric disorders are allowable if the depressive disorder diagnosis is considered to be the primary problem
. MADRS suicide item \> 4 or other indication of acute suicidality
. History of inpatient psychiatric hospitalization in the last year;
. History of suicidal ideation in the last 6 months, operationalized as a 'yes' response to item 4 or 5 in the "Suicidal Ideation" section of the Columbia-Suicide Severity Rating Scale (CSSRS)
. Any suicidal behavior in the last year (operationalized as a 'yes' response to any item in the "Suicidal Behavior" section of the CSSRS, including actual interrupted, aborted, or preparatory acts)