Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing
Condition: Depressive Disorder
MeSH terms: Depressive Disorder
Intervention: Carbidopa/levodopa; Placebo; Exercise training; Control
Intervention description: L-DOPA is the immediate precursor of dopamine, is converted to dopamine in presynaptic dopaminergic nerve terminals, and enhances dopaminergic transmission in multiple brain regions. Subjects assigned to L-DOPA will begin with a Week 1 L-DOPA daily dosage of 150mg, or 1.5 25mg carbidopa/100mg levodopa tablets at 9am and placebo tablets at
1pm and 5pm. In Week 2 the L-DOPA daily dose will increase to 300mg (1.5 25mg carbidopa/100mg levodopa tablets at 9am and 5pm, with placebo at 1pm), followed by a Week 3 to 8 L-DOPA daily dose of 450mg (1.5 25mg carbidopa/100mg levodopa tablets three times daily). Subjects assigned to placebo will take 1.5 placebo tablets three times daily for three weeks. Individuals will be instructed to maintain the same timing of doses throughout the study. Individuals unable to tolerate an increased dose will have their dosage reduced to the maximum previously tolerated dose.; Carbidopa/levodopa matched placebo; Subjects assigned t Exercise will exercise individually at their home on a program set each week by Dr. Sloan and the research assistant (RA) coach, who will work with the patient to ensure they train according to the program at the appropriate level of intensity. Subjects will select from a series of aerobic activities and for Weeks 1-2 will train at 55-65 percent of maximum HR as established during their qualifying CPET. In Weeks 3-4, they will increase exercise intensity to 65-75 percent of maximum HR, and in Weeks 5-12 they will train at 75 percent of maximum HR.; Control will engage in a series of stretches and toning exercises designed to promote flexibility and improve core strength.
Intervention MeSH terms: Levodopa; Carbidopa; Carbidopa, levodopa drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-Blind
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1.0
Sex: All
Minimum age: 60 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: slowed Information processing speed; slowed gait speed

Summary:

      In this new research study, 80 adults aged > 60 years with a significant depressive disorder
      and slowed processing and/or gait speed will be randomized to receive levodopa (L-DOPA; which
      the Candidate has previously shown to increase psychomotor speed and decrease depressive
      symptoms in older adults), aerobic exercise (itself an effective antidepressant treatment as
      monotherapy), or their combination in a 2x2 design incorporating placebo and a
      stretching/toning control. Participants will be evaluated before and after this 12-week
      duration study across cognitive domains, psychiatric symptoms, gait kinematics and mobility,
      and task-based magnetic resonance imaging (MRI) focused on effort-based decision making and
      reward processing. Data from this study will contribute toward the development of improved
      treatment and prevention strategies to maximize the functioning and active healthspan of
      older adults with neuropsychiatric disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged greater than or equal to 60 years

          2. Diagnostic and Statistical Manual (DSM) 5 MDD, Dysthymia, or Depression Not Otherwise
             Specified (NOS)

          3. Hamilton Rating Scale for Depression (HRSD) greater than or equal to 18

          4. Decreased processing speed (defined as 1 SD below age-adjusted norms on the Digit
             Symbol Test) or decreased gait speed (defined as average walking speed over 15' course
             less than 1m/s)

          5. Willing to and capable of providing informed consent and complying with study
             procedures

        Exclusion Criteria:

          1. Substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12
             months

          2. History of psychosis, psychotic disorder, mania, or bipolar disorder

          3. Probable Alzheimer's Disease, Vascular Dementia, or Parkinson's disease

          4. Mini Mental Status Examination (MMSE) less than or equal to 24

          5. HRSD suicide item greater than 2 or Clinical Global Impressions (CGI) Severity score
             of 7 at baseline

          6. Current or recent (within the past 4 weeks) treatment with antidepressants,
             antipsychotics, or mood stabilizers

          7. History of allergy, hypersensitivity reaction, or severe intolerance to
             levodopa/carbidopa

          8. Any physical or intellectual disability adversely affecting ability to complete
             assessments, including physical inability to perform treadmill testing and exercise
             protocol

          9. Acute, severe, or unstable medical or neurological illness

         10. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar
             spine disease, history of joint replacement surgery, or history of spine surgery

         11. Contraindication to magnetic resonance imaging