Clinical Trial: Inflammation-related Alterations in Neurocircuitry: Reversal With Levodopa

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: "Inflammation-related Alterations in Neurocircuitry: Reversal With Levodopa"; "Inflammation Effects on Corticostriatal Connectivity and Reward: Role of Dopamine"

Brief Summary: The purpose of this study is to learn more about the changes that happen in the brain and the body when a person is depressed. This study will determine if the level of inflammation in the body is related to symptoms of depression, how well the person thinks, and how certain brain regions communicate.

Detailed Summary: Cytokines released by an activated immune system have been associated with decreased brain dopamine and the development of depression. Biomarkers of inflammation, such as inflammatory cytokines and acute-phase proteins like C-reactive protein (CRP), are elevated in a significant proportion of patients with mood and psychiatric disorders. The investigators will study if administration of Levodopa (L- 3,4-dihydroxyphenylalanine [DOPA]-carbidopa, 250/25mg) to depressed patients with high inflammation will 1) increase corticostriatal functional connectivity, and 2) improve objective measures of motivation compared to placebo.
Sponsor: Emory University

Current Primary Outcome:

  • Change in functional corticostriatal connectivity [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    Corticostriatal connectivity will be assessed by functional magnetic resonance imaging (fMRI). Resting-state fMRI scans will be conducted on a 3 Tesla Siemens Trio MRI scanner.
  • Correlation coefficient between change in corticostriatal connectivity and levels of immune markers [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    Peripheral blood samples will be analyzed for levels of immune markers like plasma C-reactive protein (CRP), interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), tumor necrosis factor (TNF) -alpha, soluble cytokine receptor2 (TNFR 2), interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1).
  • Change in cerebral blood flow (CBF) [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The cerebral blood flow (CBF) before and after Sinemet (100mg levodopa/ 25mg carbidopa) or placebo administration will be assessed by arterial spin labeling (ASL) fMRI.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effort-Expenditure for Rewards Task (EEfRT) neurocognitive test [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Effort-Expenditure for Rewards Task (EEfRT) is a computer-based multi-trial task that will be used to objectively assess motivation.
  • The Trail Making Test (TMT) neurocognitive assessment [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Trail Making Test (TMT) will be used to measure basic attention and psychomotor processing speed.
  • Digit Symbol Task neurocognitive test [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Digit Symbol Task will be used to assess graphomotor speed, visual scanning and memory.
  • Finger Tapping Task (FTT) neurocognitive test [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Finger Tapping Task (FTT) assesses motor speed and can detect subtle motor impairment.
  • Reaction Time Task (CANTAB) neurocognitive test [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The CANTAB reaction time tests, including simple and choice reaction time tasks, will be used.
  • Multidimensional Fatigue Inventory (MFI) self-report questionnaire [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Multidimensional Fatigue Inventory (MFI) is a self-report, 20-item questionnaire that evaluates the presence and severity of fatigue.
  • Snaith-Hamilton Pleasure Scale (SHAPS) self-report questionnaire [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item scale used to assess present-state hedonic tone.
  • Inventory of Depressive Symptoms-Self Report (IDS-SR) questionnaire [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Inventory of Depressive Symptoms-Self Report (IDS-SR) questionnaire is a 30-item self-report questionnaire to measure depressive symptom severity.
  • Beck Depression Inventory (BDI-II), Anhedonia Subscale questionnaire [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Beck Depression Inventory (BDI-II), Anhedonia Subscale questionnaire is a subscale of the 21-item self-report measure of depressive symptoms.
  • Profile of Mood States (POMS) scale [ Time Frame: Visit 2 (1-2 weeks from Screening), Visit 3 (2-4 weeks from Screening) ]
    The Profile of Mood States (POMS) scale is a psychological rating scale used to assess transient, distinct mood states.


Original Secondary Outcome: Same as current

Information By: Emory University

Dates:
Date Received: July 29, 2015
Date Started: July 2015
Date Completion: June 2020
Last Updated: November 1, 2016
Last Verified: November 2016