CompletedNCT04723147Updated Dec 16, 2024Results posted

DTA (Dopaminergic Therapy for Anhedonia) Study

A Phase 4 interventional study of Carbidopa Levodopa and Placebo in Depression and Anhedonia, sponsored by Emory University. Completed at 1 site in United States. Open to participants aged 25 Years to 55 Years. Per ClinicalTrials.gov, last updated 2024-12-16.

Sponsored by Emory University · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 19
Allocation: Randomized
Ages: 25 Years to 55 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Depression
Anhedonia

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Keywords

Depression
Anhedonia

In context

Depression

8,240 studies on the registry are indexed under Depression; 1,641 are open to participants now.

This study's enrollment of 19 is below the median of 84 across 6,869 interventional studies indexed under Depression.

Browse Depression studies →

Lead sponsor

Emory University is the lead sponsor of 1,405 studies on the registry; 233 are open to participants now.

Of its 233 completed or terminated interventional studies of FDA-regulated products, 176 (76%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 25 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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).

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 19 participants (actual)

Study arms

Experimental
Carbidopa Levodopa followed by Placebo
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
Experimental
Placebo followed by Carbidopa Levodopa
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

DrugCarbidopa Levodopa
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
DrugPlacebo
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

What researchers measure

Primary outcomes

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.
Time frame: 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

Effort-Expenditure for Rewards Task (EEfRT)
The EEfRT is a widely used, multi-trial task in which participants are given an opportunity on each trial to choose between two different task difficulty levels in order to obtain monetary rewards. EEfRT will be used as an objective measure of motivation and will be administered following MRI scans during the study. The EEfRT is reported as the percent of high effort trials selected. A higher percentage reflects higher motivation for effort expenditure.
Time frame: 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
Anhedonia symptoms experienced over the past 7 days will be assessed from a subscale of the Inventory of Depressive Symptomatology- Self-Report (IDS-SR), a widely used self-report for measuring depression severity. The anhedonia subscale score is created by summing responses to items #8 (responsiveness of mood to good or desired events), #19 (general interest), and #21 (capacity for pleasure). Total anhedonia subscale scores range from 0-9 with higher scores reflecting greater anhedonia.
Time frame: 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 )
The Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) is a clinician-administered version of a validated tool for assessing hedonic tone. The SHAPS-C uses 14 questions. If "Strongly disagree" or "disagree" is chosen as the answer, item receives a score of 1 per question. If "Strongly agree" or "agree" is chosen, item receives a score of 0; then sum the scores. Total possible score ranges from 0 to 14, with higher scores reflecting greater pathology (worse study outcome).
Time frame: 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)
The Motivation and Pleasure-Self-Report (MAP-SR) will be used to capture self-reported aspects of anhedonia and reduced motivation. The scale uses 18 question each rated on a Likert scale of 0-4. Total possible score ranges from 18 to 72, with higher scores reflecting worse outcome.
Time frame: 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
The anhedonia and motivation-related item from the clinician administered Hamilton Depression Rating Scale (HAM-D) (item #7: work and activities) will be used to measure anhedonia. This item is rated on a scale of 0-4 with higher scores reflecting worse outcome.
Time frame: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)

Results

Posted Dec 16, 2024

Participant flow

First Intervention

Participant flow — First Intervention
Milestone	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa
Started	10	9
Completed	10	9
Not completed	0	0

Second Intervention

Participant flow — Second Intervention
Milestone	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa
Started	10	8
Completed	10	8
Not completed	0	0

Outcome measures

PrimaryTargeted 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.

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · Mean subject-level FC Z scores

Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) Connectivity
Mean subject-level FC Z scores	All Participants
Baseline	0.183 ± 0.132
Week 1 post- placebo	0.219 ± 0.125
Week 1 post L-DOPA (150 mg/day)	0.275 ± 0.133
Week 1 post L-DOPA (300 mg/day)	0.202 ± 0.134
Week 1 post L-DOPA (450 mg/day)	0.287 ± 0.135

SecondaryEffort-Expenditure for Rewards Task (EEfRT)

The EEfRT is a widely used, multi-trial task in which participants are given an opportunity on each trial to choose between two different task difficulty levels in order to obtain monetary rewards. EEfRT will be used as an objective measure of motivation and will be administered following MRI scans during the study. The EEfRT is reported as the percent of high effort trials selected. A higher percentage reflects higher motivation for effort expenditure.

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · percentage of choices

Effort-Expenditure for Rewards Task (EEfRT)
percentage of choices	All Participants
Baseline	0.369 ± 0.198
Week 1 post-placebo	0.300 ± 0.165
Week 1 post L-DOPA (150 mg/day)	0.368 ± 0.145
Week 1 post L-DOPA (300 mg/day)	0.322 ± 0.153
Week 1 post L-DOPA (450 mg/day)	0.330 ± 0.154

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

Anhedonia symptoms experienced over the past 7 days will be assessed from a subscale of the Inventory of Depressive Symptomatology- Self-Report (IDS-SR), a widely used self-report for measuring depression severity. The anhedonia subscale score is created by summing responses to items #8 (responsiveness of mood to good or desired events), #19 (general interest), and #21 (capacity for pleasure). Total anhedonia subscale scores range from 0-9 with higher scores reflecting greater anhedonia.

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · score on a scale

Inventory of Depressive Symptomatology- Self-Report (IDS-SR) Anhedonia Scale
score on a scale	All Participants
Baseline	5.2 ± 2.0
Week 1 post-placebo	3.0 ± 2.1
Week 1 post L-DOPA (150 mg/day)	2.5 ± 1.5
Week 1 post L-DOPA (300 mg/day)	2.4 ± 1.8
Week 1 post L-DOPA (450 mg/day)	3.2 ± 1.7

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

The Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) is a clinician-administered version of a validated tool for assessing hedonic tone. The SHAPS-C uses 14 questions. If "Strongly disagree" or "disagree" is chosen as the answer, item receives a score of 1 per question. If "Strongly agree" or "agree" is chosen, item receives a score of 0; then sum the scores. Total possible score ranges from 0 to 14, with higher scores reflecting greater pathology (worse study outcome).

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · score on a scale

Hedonic Capacity as Measured by the Snaith Hamilton Pleasure Clinician Scale (SHAPS-C )
score on a scale	All Participants
Baseline	9.7 ± 4.1
Week 1 post-placebo	5.6 ± 5.4
Week 1 post L-DOPA (150 mg/day)	3.9 ± 4.3
Week 1 post L-DOPA (300 mg/day)	4.9 ± 5.1
Week 1 post L-DOPA (450 mg/day)	5.3 ± 5.2

SecondaryMotivation and Pleasure-Self-Report (MAP-SR)

The Motivation and Pleasure-Self-Report (MAP-SR) will be used to capture self-reported aspects of anhedonia and reduced motivation. The scale uses 18 question each rated on a Likert scale of 0-4. Total possible score ranges from 18 to 72, with higher scores reflecting worse outcome.

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · mean MAP-SR total score

Motivation and Pleasure-Self-Report (MAP-SR)
mean MAP-SR total score	Carbidopa Levodopa (150, 300, 450 mg/Day Per Week) Followed by Placebo
Baseline	22.4 ± 9.9
Week 1 post-placebo	35.0 ± 13.4
Week 1 post L-DOPA (150 mg/day)	35.4 ± 7.0
Week 1 post L-DOPA (300 mg/day)	35.3 ± 5.2
Week 1 post L-DOPA (450 mg/day)	33.5 ± 8.0

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

The anhedonia and motivation-related item from the clinician administered Hamilton Depression Rating Scale (HAM-D) (item #7: work and activities) will be used to measure anhedonia. This item is rated on a scale of 0-4 with higher scores reflecting worse outcome.

Time frame:: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Reported as:: Mean · score on a scale

Hamilton Depression Rating Scale (HAM-D) Anhedonia and Motivation Item
score on a scale	Carbidopa Levodopa (150, 300, 450 mg/Day Per Week) Followed by Placebo
Baseline	3.0 ± 0.3
Week 1 post-placebo	1.9 ± 1.1
Week 1 post L-DOPA (150 mg/day)	1.6 ± 1.1
Week 1 post L-DOPA (300 mg/day)	1.3 ± 0.9
Week 1 post L-DOPA (450 mg/day)	1.8 ± 1.0

Adverse events

Collected over From time of treatment onset (placebo or carbidopa levodopa) up to 6-weeks post-intervention, about 2 months total. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Carbidopa Levodopa, 150 mg	0/18 (0%)	0/18 (0%)	12/18 (66.7%)
Carbidopa Levodopa, 300 mg	0/18 (0%)	0/18 (0%)	11/18 (61.1%)
Carbidopa Levodopa 450 mg	0/18 (0%)	0/18 (0%)	11/18 (61.1%)
Placebo	0/19 (0%)	0/19 (0%)	5/19 (26.3%)

Most frequent other events

Showing 10 of 40

Most frequent other events
Event	Carbidopa Levodopa, 150 mg	Carbidopa Levodopa, 300 mg	Carbidopa Levodopa 450 mg	Placebo
HeadacheNervous system disorders	3/18	7/18	6/18	1/19
Mild NauseaGastrointestinal disorders	3/18	3/18	1/18	1/19
InsomniaGeneral disorders	2/18	1/18	0/18	0/19
Muscle pain (soreness)General disorders	2/18	0/18	2/18	0/19
FatigueGeneral disorders	0/18	2/18	2/18	0/19
Mild Blurry vision when adjusting to glassesEye disorders	1/18	0/18	0/18	1/19
Back PainMusculoskeletal and connective tissue disorders	1/18	1/18	1/18	1/19
IrritabilityNervous system disorders	1/18	0/18	0/18	0/19
Head LacerationInjury, poisoning and procedural complications	1/18	0/18	0/18	0/19
ParesthesiaNervous system disorders	1/18	0/18	0/18	0/19

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa	Total
Mean	34.3 ± 9.0	39.4 ± 8.6	36.7 ± 9.0

Sex: Female, Male
Sex: Female, Male(Participants)	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa	Total
Female	10	7	17
Male	0	2	2

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa	Total
Count of participants	—	—	0

Region of Enrollment
Region of Enrollment(participants)	Carbidopa Levodopa Followed by Placebo	Placebo Followed by Carbidopa Levodopa	Total
United States	10	9	19

Study locations

1 site

Emory University Hospital
Atlanta, Georgia 30322, United States

References and documents

Study documents

Protocol and statistical analysis plan · Aug 23, 2023
Informed consent form · Apr 28, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Only the data - raw and analyzed, or both, depending on the items. Statistical plans an additional information may be shared within the data base but it is not required as the data will be linked to the publications.

Supporting information: Statistical analysis plan

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.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2021 to primary completion in Oct 2023, 32 months.

Results were first posted in Dec 2024, 1 year 2 months after primary completion.

Of 131 non-industry phase 4 interventional studies under Depression, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 59. This study's 32 months is close to that.

Counting every sponsor, half of 150 studies reached it within 32 months; a quarter within 17 and three quarters within 58.

How these figures are worked out, and which studies are left out of them.

Registered: Jan 21, 2021
First posted: Jan 25, 2021
StartActual: Jan 29, 2021
Primary completionActual: Oct 11, 2023
CompletionActual: Oct 11, 2023
Results first posted: Dec 16, 2024
Last update: Dec 16, 2024

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Dec 16, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04723147
Lead sponsor: Emory University
Collaborators: National Institute of Mental Health (NIMH)
Responsible party: Jennifer Felger (Associate Professor, Emory University) — Principal investigator
First posted: Jan 25, 2021
Start date: Jan 29, 2021
Primary completion: Oct 11, 2023
Completion: Oct 11, 2023
Results posted: Dec 16, 2024
Last update: Dec 16, 2024

Study contacts

Jennifer Felger, PhD

principal investigator · Emory University

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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