Dopaminergic Therapy for Anhedonia - 2

Last updated: January 16, 2025
Sponsor: Emory University
Overall Status: Active - Recruiting

Phase

4

Condition

Depression

Treatment

Placebo

Carbidopa Levodopa

Clinical Study ID

NCT06075771
STUDY00006669
R33MH121625-02
  • Ages 25-55
  • All Genders

Study Summary

The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Seventy male and female participants with depression, between 25-55 years of age, with higher levels of inflammation and anhedonia will be randomized to receive L-DOPA or matched placebo over 8 weeks. Participants will complete lab tests, medical and psychiatric assessments, motivation and motor tasks, and MRI scans as part of the study. The total length of participation is approximately 10 to 12 weeks.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • a. willing and able to give written informed consent

  • b. men or women, 25-55 years of age

  • c. a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition (DSM-5), current, as diagnosed by the Structured Clinical Interviewfor DSM-5

  • d. score of >10 on the Patient Health Questionnaire-9 (PHQ-9) or HAM-D score ≥18

  • e. off all antidepressant or other psychotropic therapy (e.g. mood stabilizers,antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks prior tobaseline visit (8 weeks for fluoxetine)

  • f. c-reactive protein (CRP) ≥2 mg/L

  • g. PHQ-9 anhedonia score ≥2

Exclusion

Exclusion Criteria:

  • a. history or evidence (clinical or laboratory) of an autoimmune disorder

  • b. history or evidence (clinical or laboratory) of hepatitis B or C infection orhuman immunodeficiency virus infection

  • c. history of any type of cancer requiring treatment with more than minor surgery

  • d. unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, orneurologic disease (as determined by physical examination, EKG and laboratorytesting)

  • e. history of any (non-mood-related) psychotic disorder; active psychotic symptomsof any type; history or current bipolar disorder; history or current gamblingdisorder; substance abuse/dependence within 6 months of study entry (as determinedby standardized clinician interview)

  • f. active suicidal plan as determined by a score >3 on item #3 on the HAM-D

  • g. an active eating disorder (except for patients with binge eating disorder in whombinging is clearly associated with worsening of mood symptoms)

  • h. a history of a cognitive disorder or traumatic head injury involving loss ofconsciousness

  • i. pregnancy or lactation

  • j. use of gender affirming hormone therapy

  • k. chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg ofaspirin), glucocorticoid containing medications or statins

  • l. use of NSAIDS, glucocorticoids, or statins at any time during the study

  • m. urine toxicology screen is positive for drugs of abuse, n. any contraindicationfor MRI scanning

  • o. intolerance, sensitivity or contraindication to carbidopa-levodopa (includinghistory of narrow-angle glaucoma, melanoma, gastric and/or duodenal ulcers, bleedingdisorders, or frequent migraines)

Study Design

Total Participants: 70
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 4
Study Start date:
November 21, 2023
Estimated Completion Date:
January 31, 2027

Study Description

Depression is a widespread disorder (lifetime prevalence >20%). Current antidepressant medications are effective for many patients; however, more than 30% fail to respond. Of the patients that do respond to treatment, some continue to suffer with primary symptoms of depression like an inability to experience pleasure, called anhedonia. In this regard, one biological pathway that may contribute to symptoms of depression and particularly anhedonia is inflammation.

The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Despite evidence of low dopamine function in patients with depression, the ability of existing dopaminergic therapies, like L-DOPA, to affect brain circuits in depression has yet to be explored. This study will help determine whether an FDA-approved medication, Sinemet (L-DOPA), might be used in the future to treat sub-groups of depressed individuals.

Seventy male and female participants with depression, between 25-55 years of age, with higher levels of inflammation and anhedonia will be randomized to receive L-DOPA or matched placebo over 8 weeks. Participants will complete lab tests, medical and psychiatric assessments, motivation and motor tasks, and MRI scans as part of the study. The total length of participation is approximately 10 to 12 weeks.

Connect with a study center

  • Emory University Hospital

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.