Back to resultsL-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
Primary Purpose
Major Depressive Disorder, Dysthymia, Depression
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
L-DOPA
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Depressive symptoms, Cognitive problems, Antidepressant non-response, Dopamine system, Older Adults, Motor slowing
Eligibility Criteria
Inclusion Criteria:
- Aged 60 years and older
- DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified
- Hamilton Rating Scale for Depression (HRSD) > 15
- Decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed (defined as average walking speed over 15' course < 1m/s)
- Willing to and capable of providing informed consent and complying with study procedures
- Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy) have been discussed and the individual agrees to be involved in an experimental treatment.
Exclusion Criteria:
- Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months.
- History of or current psychosis, psychotic disorder, mania, or bipolar disorder
- Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease (PD)
- Mini Mental Status Exam (MMSE) < 25
- HRSD ≥ 28; HRSD suicide item > 2 or the presence of significant suicide risk as judged by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline.
- Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers.
- History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA
- Acute, severe, or unstable medical or neurological illness
Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, mobility limiting history of joint replacement surgery, or history of spine surgery
FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY:
- Having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures
- History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)
Sites / Locations
- New York State Psychiatric Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
L-DOPA Arm
Placebo Arm
Arm Description
Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose
Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.
Outcomes
Primary Outcome Measures
Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Secondary Outcome Measures
Digit Symbol Test
The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Single Task Gait Speed
Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Inventory of Depressive Symptomatology--Self Report (IDS-SR)
The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Pattern Comparison Test
This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Letter Comparison Test
Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Full Information
NCT ID
NCT03761030
First Posted
November 29, 2018
Last Updated
May 18, 2023
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT03761030
Brief Title
L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
Official Title
Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
The project end date was reached prior to the full sample enrollment
Study Start Date
January 9, 2019 (Actual)
Primary Completion Date
September 8, 2021 (Actual)
Study Completion Date
September 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute
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
Individuals with Late Life Depression (LLD) often have cognitive problems, particularly problems with memory, attention, and problem solving, all of which contribute to antidepressant non-response. Our group and others have shown that decreased thinking speed is the central cause of functional problems in patients with LLD. Similarly, decreased walking speed is associated with depression and carries additional risk for falls, hospitalization, and death. Available evidence suggests that declining functionality in the brain's dopamine system contributes to age-related cognitive and motor slowing. The central hypothesis of this study is that by enhancing dopamine functioning in the brain and improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms in older adults.
Detailed Description
Enrolled participants were aged 60 and older with (1) a DSM 5 depressive disorder, (2) significant depressive symptoms, and (3) decreased thinking or walking speed will receive 8 weeks of treatment with L-DOPA up to 450mg. We will test whether L-DOPA increases brain dopamine release using neuroimaging and whether it speeds up thinking and walking speed. Data collected in the proposed studies may help identify a new treatment for LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD. This project also will elucidate the neurobiology of slowing at molecular, structural, and functional levels of analysis, increasing our understanding of the interplay between these aging-associated processes and the pathophysiologic changes underlying late life neuropsychiatric disorders. Exploring patient characteristics that predict response to L-DOPA may provide useful information to guide differential therapeutics and develop personalized medicine for LLD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Dysthymia, Depression
Keywords
Depressive symptoms, Cognitive problems, Antidepressant non-response, Dopamine system, Older Adults, Motor slowing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double Blind
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-DOPA Arm
Arm Type
Experimental
Arm Description
Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks. Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.
Intervention Type
Drug
Intervention Name(s)
L-DOPA
Other Intervention Name(s)
carbidopa/levodopa (Sinemet)
Intervention Description
We will be using generic sinemet 25/100 tablets in this study.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Placebo
Intervention Description
25/100 placebo tablets
Primary Outcome Measure Information:
Title
Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
Description
The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
Secondary Outcome Measure Information:
Title
Digit Symbol Test
Description
The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
Title
Single Task Gait Speed
Description
Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
Title
Inventory of Depressive Symptomatology--Self Report (IDS-SR)
Description
The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
Title
Pattern Comparison Test
Description
This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
Title
Letter Comparison Test
Description
Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
Time Frame
Change from Baseline to 8 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 60 years and older
DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified
Hamilton Rating Scale for Depression (HRSD) > 15
Decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed (defined as average walking speed over 15' course < 1m/s)
Willing to and capable of providing informed consent and complying with study procedures
Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy) have been discussed and the individual agrees to be involved in an experimental treatment.
Exclusion Criteria:
Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months.
History of or current psychosis, psychotic disorder, mania, or bipolar disorder
Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease (PD)
Mini Mental Status Exam (MMSE) < 25
HRSD ≥ 28; HRSD suicide item > 2 or the presence of significant suicide risk as judged by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline.
Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers.
History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA
Acute, severe, or unstable medical or neurological illness
Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, mobility limiting history of joint replacement surgery, or history of spine surgery
FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY:
Having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures
History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bret Rutherford, MD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
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