Dopaminergic Therapy for Anhedonia - 2

NCT ID: NCT06075771

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-21
• Study Completion Date: 2027-01-31

Brief 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.

Detailed 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.

Conditions

Anhedonia; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Carbidopa Levodopa Group

Patients randomized to the Carbidopa Levodopa Group will receive one tablet per day of L-DOPA (150 mg levodopa administered with 37.5 mg carbidopa) for 4 weeks.

Patients that respond after the initial 4 weeks will continue on the same dose for an additional 4 weeks to determine whether clinical response at the 150 mg dose is sustained over time compared to placebo.

Patients that do not exhibit a clinical response (50% reduction in HAM-D scores from baseline) after 4-weeks on the 150 mg dose will escalate to 450 mg L-DOPA (three tablets per day of 150 mg levodopa administered with 37.5 mg carbidopa) and studied over an additional 4 weeks (8 weeks total in the study).

Group Type: EXPERIMENTAL

Carbidopa Levodopa

Intervention Type: DRUG

Patients will receive between one and three tablets per day of 150 mg L-DOPA (administered with 37.5 mg carbidopa) to achieve doses ranging from 150 to 450 mg/day.

Placebo Group

Participants will receive placebo tablet. Placebo-treated non-responders at 4 weeks will remain on placebo but with the same instructions to increase daily pill intake.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive between one and three placebo tablets per day matching the Carbidopa Levodopa tablet.

Interventions

Carbidopa Levodopa

Patients will receive between one and three tablets per day of 150 mg L-DOPA (administered with 37.5 mg carbidopa) to achieve doses ranging from 150 to 450 mg/day.

Intervention Type: DRUG

Placebo

A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive between one and three placebo tablets per day matching the Carbidopa Levodopa tablet.

Intervention Type: DRUG

Other Intervention Names

Sinemet, L-DOPA; Placebo tablet

Eligibility Criteria

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 Interview for 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 to baseline visit (8 weeks for fluoxetine)
• f. c-reactive protein (CRP) ≥2 mg/L
• g. PHQ-9 anhedonia score ≥2

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 or human immunodeficiency virus infection
• c. history of any type of cancer requiring treatment with more than minor surgery
• d. unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing)
• e. history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; history or current bipolar disorder; history or current gambling disorder; substance abuse/dependence within 6 months of study entry (as determined by 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 whom binging is clearly associated with worsening of mood symptoms)
• h. a history of a cognitive disorder or traumatic head injury involving loss of consciousness
• i. pregnancy or lactation
• j. use of gender affirming hormone therapy
• k. chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), 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 contraindication for MRI scanning
• o. intolerance, sensitivity or contraindication to carbidopa-levodopa (including history of narrow-angle glaucoma, melanoma, gastric and/or duodenal ulcers, bleeding disorders, or frequent migraines)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Felger

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Felger, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Felger, PhD

Role: CONTACT

jfelger@emory.edu

4047273987

Facility Contacts

Jennifer Felger, PhD

Role: primary

jfelger@emory.edu

4047273987

Other Identifiers

R33MH121625-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00006669

Identifier Type: -

Identifier Source: org_study_id