Inflammation-related Alterations in Neurocircuitry: Reversal With Levodopa
Condition: Depression
MeSH terms: Inflammation
Intervention: Levodopa+carbidopa; Placebo
Intervention description: Sinemet is a combination of 250 mg levodopa and 50 mg carbidopa. Sinemet will be administered orally at Visit 1 or Visit 2.; A placebo is a sugar pill that has no therapeutic effect and will be administered orally at Visit 1 or Visit 2.
Intervention MeSH terms: Levodopa; Carbidopa
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Inflammation; Anhedonia; Psychomotor retardation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects have signed a current version of the Informed Consent and HIPAA documents
             prior to initiation of study procedures

          -  Able to comprehend English

          -  Diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM)-V major
             depression and currently off antidepressant medication, unless otherwise approved by
             the PI or PI's designee

          -  Depression as the primary axis I disorder

          -  Negative pregnancy test for women of childbearing potential

          -  Not breast feeding

          -  At least two CRP tests conducted to establish reliability

        Exclusion Criteria:

          -  Evidence of untreated or poorly controlled endocrine, cardiovascular, pulmonary,
             hematological, renal, or neurological disease

          -  History of central nervous system (CNS) trauma or active seizure disorder requiring
             medication unless otherwise approved by principal investigator, or PI's designee

          -  Current or history of migraines, glaucoma, melanoma, or bleeding disorder of any kind

          -  Autoimmune or inflammatory disorder of any kind

          -  Embedded metallic objects, prosthetics made of paramagnetic metals, aneurysmal clips
             and/or a history of claustrophobia

          -  Chronic infection (e.g. hepatitis B or C or Human Immunodeficiency Virus infection)

          -  Chronic use of agents known to affect the immune system including glucocorticoid
             therapy within the past 6 months, methotrexate within the past 1 year, chemotherapy of
             any kind (past or present), immunotherapy of any kind (past or present), aspirin or
             non-steroidal anti-inflammatory drugs (NSAIDs; within the past 2 weeks), statins
             (within the past 1 month), vaccinations (within the past 2 weeks), topical steroids
             (within the past 2 weeks), and antibiotics (within the past two weeks) unless
             otherwise approved by principal investigator or PI's designee.

          -  Suicide attempt within six months of screening, or active suicidal intent or plan, or
             score >2 on Hamilton Depression Rating Scale (HDRS), or Quick Inventory of Depressive
             Symptomatology Self-Report (QIDS) or Patient Health Questionnaire (PHQ-9) Suicide
             Item, unless otherwise approved by the PI or PI's designee

          -  A positive pregnancy test

          -  Organ transplants

          -  Current or history of cancer within the past five years besides basal cell carcinoma,
             unless otherwise approved by the PI or PI's designee

          -  A score of <28 on the Mini Mental Status Exam (MMSE), unless otherwise approved by the
             PI or PI's designee

          -  Wide Range Achievement Test (WRAT-3) score indicating less than 8th grade reading
             level, unless otherwise approved by the PI or PI's designee

          -  Either QIDS <14 or PHQ-9 <15, or HDRS <18, unless otherwise approved by the principal
             investigator or PI's designee

          -  History of the following: schizophrenia, schizoaffective disorder, other (non mood
             disorder) psychosis, depression secondary to a medical condition, mental retardation,
             dementia, or delirium

          -  Substance dependence [or abuse within the past year (except nicotine)], unless
             otherwise approved by the PI or PI's designee

          -  Body Mass Index >40 to limit the impact of morbid obesity on the results, unless
             otherwise approved by the principal investigator or PI's designee

          -  Antisocial personality disorder diagnosis as assessed during clinical interview, as
             well as a history of hospitalization and/or recurrent suicidal behavior judged to be
             directly due to the personality disorder

          -  Current eating disorder (except binge eating related to depression) unless approved by
             PI or PI's designee

          -  Current obsessive-compulsive disorder (OCD), exclusionary only if impacting daily
             functioning, as assessed by clinical interview

          -  Any other condition which in the opinion of the investigator would make the patient
             unsuitable for enrollment, or could interfere with participating in or completing the
             protocol

          -  Smoking more than 1/2 pack a day or e-cigarette equivalent, unless approved by the PI
             or PI's designee

          -  Initiation of any of the following medications, unless otherwise approved by the PI or
             PI's designee: Aspirin or Aspirin-like compounds, Ibuprofen or Naproxen Sodium,
             Cholesterol medications, Antibiotics, Herbal Medications, Psychiatric or Psychotropic
             Medications, Omega-3 supplements, Topical Steroids, Vaccinations

          -  Currently on antidepressant medication, unless otherwise approved by the PI or PI's
             designee