AnhedoniaPhase 4DTA-2NCT06075771
Dopaminergic Therapy for Anhedonia - 2
A Phase 4 study testing Carbidopa Levodopa in people with Anhedonia and Depression, run by Emory University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 25 to 55 years
- Conditions the study is for
- Anhedonia, Depression
- What is being tested?
- Carbidopa Levodopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2023to Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Emory University Hospital
Atlanta, Georgia, 30322
Jennifer Felger, PhD, 4047273987, jfelger@emory.edu
About this study
Official title: Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression - 2
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.
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 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
- Being tested
- Carbidopa Levodopa, Placebo
- Keywords
- Anhedonia, Depression
- Medical subject headings
- Anhedonia, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbidopa LevodopaDrug
Also called Sinemet, L-DOPA
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.
PlaceboDrug
Also called Placebo tablet
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Secondary outcomes (5)
Change in corticostriatal functional connectivity (FC) in reward circuits
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. Higher FC Z scores reflect stronger connectivity.
Measured: Baseline, week 4 post-intervention, week 8 post-intervention
Change in objective motivation assessed by 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.
Measured: Baseline, week 4 post-intervention, week 8 post-intervention
Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)
Anhedonia will be assessed from a subscale of the IDS-SR. Scores on this 3-question scale range from 0-9 with higher scores reflecting greater anhedonia.
Measured: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)
The SHAPS-C is a clinician administered tool to assess symptoms of anhedonia. The SHAPS-C uses14 questions each rated on a Likert scale of 1-4, with higher scores reflecting greater pathology.
Measured: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Motivation and Pleasure-Self-Report (MAP-SR)
The MAP-SR will be used to capture self-reported aspects of anhedonia and reduced motivation. The scale uses 18 questions each rated on a Likert scale of 0-4, with higher scores reflecting greater pathology.
Measured: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start21 Nov 2023
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnhedoniaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2:1 randomization to L-DOPA versus placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Jennifer Felger, Emory University
- Investigators
- Jennifer Felger, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06075771
- Sponsor's protocol ID
- STUDY00006669
- Other IDs
- R33MH121625-02
- Acronym
- DTA-2
- Status last verified
- Jan 2026
- First submitted
- 4 Oct 2023
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression - 2
- ClinicalTrials.gov ID
- NCT06075771
- Acronym / sponsor ID
- DTA-2 / STUDY00006669
- Conditions
- Anhedonia, Depression
- Keywords
- Anhedonia, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 21 Nov 2023 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 10 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 2:1 randomization to L-DOPA versus placebo
| Arm | Type | Receives |
|---|---|---|
| Carbidopa Levodopa Group | Experimental | Drug: Carbidopa LevodopaPatients 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). |
| Placebo Group | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carbidopa LevodopaAlso: Sinemet, L-DOPAPatients 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. | Drug | Carbidopa Levodopa Group |
| PlaceboAlso: Placebo tabletA 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. | Drug | Placebo Group |
Primary outcome
Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
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.
5 secondary outcomes
Change in corticostriatal functional connectivity (FC) in reward circuits
Time frame: Baseline, week 4 post-intervention, week 8 post-intervention
Change in objective motivation assessed by Effort-Expenditure for Rewards Task (EEfRT)
Time frame: Baseline, week 4 post-intervention, week 8 post-intervention
Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Motivation and Pleasure-Self-Report (MAP-SR)
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer Felger, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carbidopa Levodopa in people with Anhedonia and Depression, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Felger, PhD (4047273987, jfelger@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D) (time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.