RECRUITING

Dopaminergic Dysfunction in Late-Life Depression

Conditions

Late Life Depression Cognitive Decline Depressive Disorder, Treatment-Resistant Levodopa Gait Impairment Antiparkinson agent Elderly Depressive Disorder, major

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Dopaminergic Dysfunction in Late-Life Depression

Quick Facts

Study Start:2021-02-15

Study Completion:2026-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04469959

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:60 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 60 years 2. Diagnostic and Statistical Manual-5 (DSM5) diagnosis of Major Depressive Disorder, Persistent Depressive Disorder, or Depression Not Otherwise Specified (NOS) 3. MADRS score ≥ 15 4. 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) 5. Capable of providing informed consent and adhering to study procedures	1. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) in the past 12 months 2. 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 3. Primary neurological disorder, including dementia, stroke, Parkinson's disease, epilepsy, etc 4. SBT \> 10 5. MADRS suicide item \> 4 or other indication of acute suicidality 6. History of inpatient psychiatric hospitalization in the last year; 7. 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) 8. 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) 9. Current or recent (within the past 2 weeks) treatment with antipsychotics or mood stabilizers, or use of antidepressants where washout is not advisable 10. History of hypersensitivity, allergy, or intolerance to Carbidopa/levodopa 11. Any physical or intellectual disability adversely affecting ability to complete assessments 12. Unstable medical illness 13. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, or history of joint replacement / spine surgery that limits mobility 14. Diagnosis of HIV 15. History of significant radioactivity exposure (nuclear medicine studies or occupational exposure).

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 60 years
2. Diagnostic and Statistical Manual-5 (DSM5) diagnosis of Major Depressive Disorder, Persistent Depressive Disorder, or Depression Not Otherwise Specified (NOS)
3. MADRS score ≥ 15
4. 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)
5. Capable of providing informed consent and adhering to study procedures

1. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) in the past 12 months
2. 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
3. Primary neurological disorder, including dementia, stroke, Parkinson's disease, epilepsy, etc
4. SBT \> 10
5. MADRS suicide item \> 4 or other indication of acute suicidality
6. History of inpatient psychiatric hospitalization in the last year;
7. 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)
8. 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)
9. Current or recent (within the past 2 weeks) treatment with antipsychotics or mood stabilizers, or use of antidepressants where washout is not advisable
10. History of hypersensitivity, allergy, or intolerance to Carbidopa/levodopa
11. Any physical or intellectual disability adversely affecting ability to complete assessments
12. Unstable medical illness
13. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, or history of joint replacement / spine surgery that limits mobility
14. Diagnosis of HIV
15. History of significant radioactivity exposure (nuclear medicine studies or occupational exposure).

Contacts and Locations

Study Contact

Warren Taylor, MD,MHSc

CONTACT

615-322-1073

warren.d.taylor@vumc.org

Carrie Williams

CONTACT

(615) 936-2162

carrie.e.williams@vumc.org

Principal Investigator

Warren Taylor, MD,MHSc

PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Study Locations (Sites)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213

United States

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212

United States

Collaborators and Investigators

Sponsor: Vanderbilt University Medical Center

Warren Taylor, MD,MHSc, PRINCIPAL_INVESTIGATOR, Vanderbilt University Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-15

Study Completion Date2026-06-30

Study Record Updates

Study Start Date2021-02-15

Study Completion Date2026-06-30

Terms related to this study

Keywords Provided by Researchers

Antiparkinson agent
Levodopa
Elderly
Depressive Disorder, major

Additional Relevant MeSH Terms

Late Life Depression
Cognitive Decline
Depressive Disorder, Treatment-Resistant
Levodopa
Gait Impairment