DTA (Dopaminergic Therapy for Anhedonia) Study

NCT04723147 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: STUDY000003611R61MH121625-01A1
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Thirty-five male and female participants with depression, between the ages of 25-55 years of age, will be randomized to two study tracks (A and B) to receive both placebo and three doses of L-DOPA, given in different orders. Increases or decreases in each dose will occur gradually over 6 weeks of the study. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing and functional MRI (fMRI) scans as part of the study. The total length of participation is about 2 months.

Conditions

Depression; Anhedonia

Keywords

Depression; Anhedonia

Outcome Measures

Primary Outcomes (1)

• Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) Connectivity

  Patients will undergo resting-state and task-based functional magnetic resonance imaging (fMRI) to calculate functional connectivity (FC) between the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions using Fisher's Z transformation {Z(R)=0.5ln\[(1+R)/(1-R)\]}. This is a standard method for calculating fMRI FC whereby higher FC Z scores reflect stronger connectivity.

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

Secondary Outcomes (5)

• Effort-Expenditure for Rewards Task (EEfRT)

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

• Inventory of Depressive Symptomatology- Self-Report (IDS-SR) Anhedonia Scale

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

• Hedonic Capacity as Measured by the Snaith Hamilton Pleasure Clinician Scale (SHAPS-C )

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

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

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

• Hamilton Depression Rating Scale (HAM-D) Anhedonia and Motivation Item

  Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

Study Arms (2)

Carbidopa Levodopa followed by Placebo

EXPERIMENTAL

Participants will receive first Carbidopa Levodopa at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day; and then placebo.

Drug: Carbidopa Levodopa; Drug: Placebo

Placebo followed by Carbidopa Levodopa

EXPERIMENTAL

Participants will receive first placebo, and then Carbidopa Levodopa (L-DOPA) at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day.

Drug: Carbidopa Levodopa; Drug: Placebo

Interventions

Carbidopa Levodopa DRUG

Patients will receive L-DOPA at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA. Starting dose is 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day

Also known as: Sinemet, L-DOPA

Carbidopa Levodopa followed by Placebo; Placebo followed by Carbidopa Levodopa

Placebo DRUG

A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive 1 placebo tablet matching the Carbidopa Levodopa tablet.

Also known as: Placebo tablet

Carbidopa Levodopa followed by Placebo; Placebo followed by Carbidopa Levodopa

Eligibility Criteria

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

You may qualify if:

• willing and able to give written informed consent;
• men or women, 25-55 years of age
• a primary diagnosis of DSM-V MD, current, as diagnosed by the SCID-I;
• score \>10 on the Patient Health Questionnaire \[PHQ\]-9
• 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)
• CRP ≥2 mg/L
• Score \>/=2 on the anhedonia question of Patient Health Questionnaire \[PHQ\]-9

You may not qualify if:

• history or evidence (clinical or laboratory) of an autoimmune disorder ;
• history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection; - history of any type of cancer requiring treatment with more than minor surgery;
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
• 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 SCID);
• 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) ;
• a history of a cognitive disorder
• pregnancy or lactation;
• chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications or statins;
• use of NSAIDS, glucocorticoids, or statins at any time during the study;
• urine toxicology screen is positive for drugs of abuse,
• any contraindication for MRI scanning; n. 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

Location

MeSH Terms

Conditions

Depression; Anhedonia

Interventions

carbidopa, levodopa drug combination; Levodopa

Condition Hierarchy (Ancestors)

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

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

Results Point of Contact

• Title: Dr. Jennifer Felger
• Organization: Emory University

jfelger@emory.edu

404-727-3987

Study Officials

• Jennifer Felger, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: January 25, 2021
• Study Start: January 29, 2021
• Primary Completion: October 11, 2023
• Study Completion: October 11, 2023
• Last Updated: December 16, 2024
• Results First Posted: December 16, 2024

Record last verified: 2024-12

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)