Dopaminergic Therapy for Anhedonia - 2

NCT06075771 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: STUDY00006669R33MH121625-02
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Anhedonia; Depression

Keywords

Anhedonia; Depression

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)

  The HAM-D-17 is a 17-item, clinician administered scale, that rates severity of depression. Each item is rated on a scale 0-4 with higher scores indicating greater pathology.

  Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention

Secondary Outcomes (5)

• Change in corticostriatal functional connectivity (FC) in reward circuits

  Baseline, week 4 post-intervention, week 8 post-intervention

• Change in objective motivation assessed by Effort-Expenditure for Rewards Task (EEfRT)

  Baseline, week 4 post-intervention, week 8 post-intervention

• Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)

  Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention

• Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)

  Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention

• Change in Motivation and Pleasure-Self-Report (MAP-SR)

  Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention

Study Arms (2)

Carbidopa Levodopa Group

EXPERIMENTAL

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).

Drug: Carbidopa Levodopa

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Carbidopa Levodopa 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.

Also known as: Sinemet, L-DOPA

Carbidopa Levodopa Group

Placebo 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.

Also known as: Placebo tablet

Placebo Group

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Anhedonia; Depression

Interventions

carbidopa, levodopa drug combination; Levodopa

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Jennifer Felger, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Felger, PhD

CONTACT

4047273987; jfelger@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 2:1 randomization to L-DOPA versus placebo

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: October 10, 2023
• Study Start: November 21, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: After publication, within one year of the end of the project.
• Access Criteria: Must be NIH investigators and they have to submit an application, including analysis plan, in order to be granted access.

Locations

US (1)