Back to resultsDTA-2: Dopaminergic Therapy for Anhedonia - 2
Primary Purpose
Anhedonia, Depression
Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Carbidopa Levodopa
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Anhedonia focused on measuring Anhedonia, Depression
Eligibility Criteria
Inclusion Criteria: a. willing and able to give written informed consent; b. men or women, 25-55 years of age; c. a primary diagnosis of DSM-V MD, current, as diagnosed by the SCID-V; d. score of >10 on the 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. CRP ≥2 mg/L, g. PHQ-9 anhedonia score ≥2. Exclusion Criteria: 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; 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)
Sites / Locations
- Emory University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Carbidopa Levodopa Group
Placebo Group
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT06075771
First Posted
October 4, 2023
Last Updated
October 4, 2023
Sponsor
Emory University
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT06075771
Brief Title
DTA-2: Dopaminergic Therapy for Anhedonia - 2
Official Title
Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression - 2
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
January 2027 (Anticipated)
Study Completion Date
January 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anhedonia, Depression
Keywords
Anhedonia, Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
2:1 randomization to L-DOPA versus placebo
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Carbidopa Levodopa Group
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carbidopa Levodopa
Other Intervention Name(s)
Sinemet, L-DOPA
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)
Description
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.
Time Frame
Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Secondary Outcome Measure Information:
Title
Change in corticostriatal functional connectivity (FC) in reward circuits
Description
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.
Time Frame
Baseline, week 4 post-intervention, week 8 post-intervention
Title
Change in objective motivation assessed by Effort-Expenditure for Rewards Task (EEfRT)
Description
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, week 4 post-intervention, week 8 post-intervention
Title
Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)
Description
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.
Time Frame
Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Title
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)
Description
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.
Time Frame
Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Title
Change in Motivation and Pleasure-Self-Report (MAP-SR)
Description
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.
Time Frame
Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
a. willing and able to give written informed consent;
b. men or women, 25-55 years of age;
c. a primary diagnosis of DSM-V MD, current, as diagnosed by the SCID-V;
d. score of >10 on the 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. CRP ≥2 mg/L,
g. PHQ-9 anhedonia score ≥2.
Exclusion Criteria:
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;
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Felger, PhD
Phone
4047273987
Email
jfelger@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Felger, PhD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Felger, PhD
Phone
404-727-3987
Email
jfelger@emory.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
After publication, within one year of the end of the project.
IPD Sharing Access Criteria
Must be NIH investigators and they have to submit an application, including analysis plan, in order to be granted access.
Learn more about this trial
DTA-2: Dopaminergic Therapy for Anhedonia - 2
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