1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
Condition: Depression; Cognitive Impairment; Gait Impairment
MeSH terms: Depression; Depressive Disorder
Intervention: Carbidopa/levodopa; Placebo
Intervention description: 150-450mg carbidopa/levodopa 3 times daily; Carbidopa/levodopa-matched placebo tablet 3 times daily
Intervention MeSH terms: Levodopa; Carbidopa; Carbidopa, levodopa drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double blind crossover study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor
      functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is
      common, predicts poor outcomes, and manifests as difficulties in motivation and effort along
      with cognitive and gait impairment. While studies of dopamine function in early and midlife
      depression primarily focus on individuals' ability to feel pleasure and respond to rewards,
      they often exclude the cognitive and physical function domains relevant for older adults
      despite a recognized decline in dopamine function with normal aging. The objectives of this
      collaborative R01 proposal between Columbia University/New York State Psychiatric Institute
      and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in
      LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular
      Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral
      / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to
      stimulation with carbidopa/levodopa (L-DOPA).
    

Eligibility criteria:

        Inclusion Criteria:

        Depressed Subjects:

          1. Age 60 years or older (female subjects will be post-menopausal by virtue of their age,
             but last menstrual period month and year will be documented in the study database)

          2. Diagnosis and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD)
             or Persistent Depressive Disorder (PDD)

          3. Montgomery Asberg Depression Rating Scale Score (MADRS) >=15

          4. Decreased processing speed or decreased gait speed

          5. Capable of providing informed consent and complying with study procedures

          6. Alternative standard treatments for MDD or PDD have been discussed and the individual
             agrees to be involved in an experimental treatment

        Psychiatrically Healthy Elders:

          1. Age 60 years or older years old

          2. MADRS < 8

          3. Capable of providing informed consent and complying with study procedures

        Exclusion Criteria:

        Depressed Subjects:

          1. Diagnosis of Substance Use Disorder (excluding Tobacco Use Disorder) in the past 12
             months

          2. History of psychosis (except brief psychosis associated with transient medical
             conditions [e.g., delirium, urinary tract infection, etc], psychotic disorder, mania,
             or bipolar disorder.

          3. Primary neurological disorder, including dementia, stroke, Parkinson's disease, or
             epilepsy.

          4. Mini Mental State Examination (MMSE) < 24

          5. MADRS suicide item >4 or other indication of acute suicidality

          6. Current or recent (within the past 2 weeks) treatment with antidepressants,
             antipsychotics, or mood stabilizers

          7. History of hypersensitivity, allergy, or intolerance to L-DOPA

          8. Any physical or intellectual disability adversely affecting ability to complete
             assessments.

          9. Acute, severe, or unstable medical illness

         10. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar
             spine disease, or history of joint replacement or spine surgery that limits mobility

         11. Contraindication to MRI scanning (Metal implants, pacemaker, metal prostheses, metal
             orthodontic appliances in the body unless there is confirmation that the substance is
             MRI compatible.)

         12. History of significant radioactivity exposure (nuclear medicine studies or
             occupational exposure)

         13. Has a medical condition managed with medication and/or device and the managing
             physician considers the condition and/or its management a contraindication to the
             research use of L-DOPA in this participant

        Psychiatrically Healthy Elders:

          1. Any personal history of DSM-5 disorder

          2. Family history of MDD in first-degree relative

          3. Plus, Exclusion criteria 8-12 above