Clinical trial NCT04723147: DTA (Dopaminergic Therapy for Anhedonia) Study
Official title: Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Anhedonia
Keywords: Depression
Anhedonia
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-01-25
Enrollment: 19
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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 6-week, double-blind, placebo-controlled, crossover 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 the best dose of an FDA-approved medication, Sinemet (L-DOPA) that might be used in the future to treat sub-groups of depressed individuals.

Forty 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) Connectivity
timeFrame: 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:
measure: Effort-Expenditure for Rewards Task (EEfRT)
timeFrame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
measure: Inventory of Depressive Symptomatology- Self-Report (IDS-SR) Anhedonia Scale
timeFrame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
measure: Hedonic Capacity as Measured by the Snaith Hamilton Pleasure Clinician Scale (SHAPS-C )
timeFrame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
measure: Motivation and Pleasure-Self-Report (MAP-SR)
timeFrame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
measure: Hamilton Depression Rating Scale (HAM-D) Anhedonia and Motivation Item
timeFrame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Jennifer Felger, PhD
role: PRINCIPAL_INVESTIGATOR
References: