DepressionPhase 4NCT04723147
DTA (Dopaminergic Therapy for Anhedonia) Study
A Phase 4 study testing Carbidopa Levodopa in people with Depression and Anhedonia, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 55 years
- Conditions the study is for
- Depression, Anhedonia
- 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
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 2021to 11 Oct 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression
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
- Depression, Anhedonia
- Being tested
- Carbidopa Levodopa, Placebo
- Keywords
- Depression, Anhedonia
- Medical subject headings
- Depression, Anhedonia
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 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
PlaceboDrug
Also called Placebo tablet
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Carbidopa Levodopa; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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, 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2021
- Study start29 Jan 2021
- Primary completion11 Oct 2023
- Study completion11 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies 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
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
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
- NCT04723147
- Sponsor's protocol ID
- STUDY00000361
- Other IDs
- 1R61MH121625-01A1
- Status last verified
- Dec 2024
- First submitted
- 21 Jan 2021
- Last updated
- 16 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression
- ClinicalTrials.gov ID
- NCT04723147
- Acronym / sponsor ID
- STUDY00000361
- Conditions
- Depression, Anhedonia
- Keywords
- Depression, Anhedonia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 29 Jan 2021 (actual)
- Primary completion
- 11 Oct 2023 (actual)
- Study completion
- 11 Oct 2023 (actual)
- First posted
- 25 Jan 2021 (actual)
- Results
- Posted 16 Dec 2024
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carbidopa Levodopa followed by Placebo | Experimental | Drug: Carbidopa Levodopa, Drug: PlaceboParticipants 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. |
| Placebo followed by Carbidopa Levodopa | Experimental | Drug: Carbidopa Levodopa, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (11 listed)
- 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) ;
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 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 | Drug | Carbidopa Levodopa followed by Placebo, Placebo followed by Carbidopa Levodopa |
| PlaceboAlso: Placebo tabletA 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. | Drug | Carbidopa Levodopa followed by Placebo, Placebo followed by Carbidopa Levodopa |
Primary outcome
Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) 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)
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.
5 secondary outcomes
Effort-Expenditure for Rewards Task (EEfRT)
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
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 )
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)
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
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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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Survivorship
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. This study is not recruiting at the moment.
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 Depression and Anhedonia, 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 11 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: finished, as of the sponsor's last update on 16 Dec 2024. 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. 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?
Yes. Results are posted in the registry (first posted 16 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) 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)). 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 16 Dec 2024.