search
Back to results

A Study of L-DOPA for Depression and Slowing in Older Adults

Primary Purpose

Major Depressive Disorder, Dysthymia, Depression Not Otherwise Specified

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Levodopa
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age >59 years
  • DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified
  • Center for Epidemiological Studies Depression (CES-D) Rating Scale > 9
  • Decreased processing speed (defined as 0.5 SD below age-adjusted norms on the Digit Symbol Test) and decreased gait speed (defined as average walking speed over 15' course < 1 m/s)
  • Willing and capable of providing informed consent and complying with study procedures
  • Prefer not to be treated with a standard treatment for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy)

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 PD
  • Mini Mental Status Exam (MMSE) < 25
  • HRSD ≥ 25 or the presence of significant suicide risk
  • 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 LDOPA
  • Acute, severe, or unstable medical or neurological illness
  • Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, history of joint replacement surgery, or history of spine surgery
  • Hypotension (SBP<90), hypertension (SBP >150 or DBP > 90), past stroke causing sensory or movement deficits, cardiac arrhythmias, or any other severe or uncontrolled cardiovascular disease
  • 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)
  • Presence of a clinically significant brain abnormality, significant anemia, insulin dependent diabetes, a history of cardiovascular disease, or uncontrolled/untreated risk factors for coronary artery disease

Sites / Locations

  • New York State Psychiatric Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

L-DOPA

Arm Description

Patients will receive titration of L-DOPA from 150 mg to 450 mg.

Outcomes

Primary Outcome Measures

Hamilton Rating Scale for Depression (24 Item)
Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The 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.

Secondary Outcome Measures

Digit Symbol Substitution Test
Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) 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 (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.
Digit Symbol Substitution Test
Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) 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 (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.
Pattern Comparison
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 reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.
Pattern Comparison
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 reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.
Letter Comparison
Subjects will be 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. The higher the number, the better the score.
Letter Comparison
Subjects will be 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. The higher the number, the better the score.
Single Task Gait Speed
Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk 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 will be completed, and gait speed will be based on the average of 2 trials.
Single Task Gait Speed
Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk 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 will be completed, and gait speed will be based on the average of 2 trials.
Dual Task Gait Speed
For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyses
Dual Task Gait Speed
For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyse.
Inventory of Depressive Symptomatology-Self Report
Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.
Inventory of Depressive Symptomatology-Self Report
Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.
Pre-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Post-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Pre-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Post-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Pre-Treatment [11C]-Raclopride Binding Potential: Associative Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Post-Treatment [11C]-Raclopride Binding Potential: Associative Striatum
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.

Full Information

First Posted
April 13, 2016
Last Updated
May 15, 2023
Sponsor
New York State Psychiatric Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT02744391
Brief Title
A Study of L-DOPA for Depression and Slowing in Older Adults
Official Title
A Study of L-DOPA for Depression and Slowing in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
August 24, 2016 (Actual)
Primary Completion Date
September 14, 2018 (Actual)
Study Completion Date
November 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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 R61/R33 Phased Innovation Award 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
This study will elucidate the neurobiology of slowing and LLD, identify a novel therapeutic target for depression, and contribute to the development of personalized treatment regimens for LLD. The multimodal neuroimaging methods detailed in this application will provide information about the neurobiology of aging-associated slowing and LLD at molecular, structural, and functional levels of analysis. These data will fill a crucial gap in our knowledge regarding what are the physiologic and functional consequences of dopamine depletion occurring across the lifespan in individuals without PD. Results from this project also will allow us to evaluate a novel therapeutic approach to LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD. Even apart from patients with LLD, cognitive and motor slowing exact a large public health burden in terms of impaired functioning and increased morbidity and mortality, and this burden will only grow as the population ages. It is critical to develop treatments capable of altering the negative health trajectories associated with slowing in order to help older adults maintain independent functioning and live longer with an increased quality of life. Finally, while PET and MRI may prove critical to understand the neurobiology of slowing and LLD, their invasiveness and expense limit their roles in informing treatment decisions in clinical practice settings. For this reason the investigators are also assessing the influence of genetic moderators such as interleukin-6 (IL-6) and catechol-O-methyl-transferase (COMT) genotype on baseline dopamine functioning and response to L-DOPA. This may facilitate the identification of both high-risk individuals and those most likely to benefit from treatment interventions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Dysthymia, Depression Not Otherwise Specified, Decreased Processing Speed, Decreased Gait Speed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L-DOPA
Arm Type
Experimental
Arm Description
Patients will receive titration of L-DOPA from 150 mg to 450 mg.
Intervention Type
Drug
Intervention Name(s)
Levodopa
Other Intervention Name(s)
L-Dopa
Primary Outcome Measure Information:
Title
Hamilton Rating Scale for Depression (24 Item)
Description
Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The 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.
Time Frame
Week 3
Secondary Outcome Measure Information:
Title
Digit Symbol Substitution Test
Description
Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) 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 (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.
Time Frame
Screening
Title
Digit Symbol Substitution Test
Description
Digit symbol substitution test (DSST) is a neuropsychological test sensitive to brain damage, dementia, age and depression. The test is not sensitive to the location of brain-damage (except for damage comprising part of the visual field). It consists of (e.g. nine) 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 (e.g. 90 or 120 sec) is measured. The higher the number, the better the score.
Time Frame
Week 3
Title
Pattern Comparison
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 reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.
Time Frame
Screening
Title
Pattern Comparison
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 reflected the number of correct items (of a possible 130) completed in 90 s; items were designed to minimize the number of errors that were made.
Time Frame
Week 3
Title
Letter Comparison
Description
Subjects will be 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. The higher the number, the better the score.
Time Frame
Screening
Title
Letter Comparison
Description
Subjects will be 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. The higher the number, the better the score.
Time Frame
Week 3
Title
Single Task Gait Speed
Description
Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk 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 will be completed, and gait speed will be based on the average of 2 trials.
Time Frame
Screening
Title
Single Task Gait Speed
Description
Patients' gait will be assessed as walking speed in m/s on a 15' walking course. Patients are instructed to walk 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 will be completed, and gait speed will be based on the average of 2 trials.
Time Frame
Week 3
Title
Dual Task Gait Speed
Description
For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyses
Time Frame
Screening
Title
Dual Task Gait Speed
Description
For the Dual Task, patients are instructed to walk at their usual pace while simultaneously verbally listing as many animals as possible. In addition, a counting Dual Task will be used in which patients are instructed to walk at their usual pace while simultaneously performing serial subtractions by three starting at 100. Patients will start and end at a point 2 meters from the Gaitrite mat to eliminate acceleration and deceleration effects. Dual Task will be assessed two times with the average used in the analyse.
Time Frame
Week 3
Title
Inventory of Depressive Symptomatology-Self Report
Description
Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.
Time Frame
Screening
Title
Inventory of Depressive Symptomatology-Self Report
Description
Rating scale for depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria that has been increasingly used in antidepressant studies due to its equivalent weightings for each item, understandable anchor points, and inclusion of all Diagnostic and Statistical Manual of Mental Disorders criteria. Patients will be asked to circle the one response to each item that best describes them for the past seven days. The answers range 0-84. The higher the score the greater the depressive symptoms.
Time Frame
Week 3
Title
Pre-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Baseline
Title
Post-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Week 3
Title
Pre-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Baseline
Title
Post-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Week 3
Title
Pre-Treatment [11C]-Raclopride Binding Potential: Associative Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Baseline
Title
Post-Treatment [11C]-Raclopride Binding Potential: Associative Striatum
Description
Subjects received 2 [11C]-raclopride positron emission tomography (PET) scans: baseline and post-L-DOPA treatment. High resolution anatomical T1-weighted MRI scans were acquired for each subject and PET data were co-registered to the MRIs using maximization of mutual information (SPM12, Wellcome Centre for Human Neuroimaging). Regions of interest (ROIs) were applied to the MRIs and transferred to the PET data and included the sensorimotor striatum (post-commissural putamen, SMST), associative striatum (whole caudate and pre-commissural putamen, AST) and the limbic striatum (nucleus accumbens and the most ventral aspects of the pre-commissural caudate and putamen, LST). Additionally, an ROI was drawn on cerebellum as a reference tissue. ROI time activity curves were derived as the average activity in each ROI in each frame. The primary outcome measure was BPND, the binding potential with respect to the non-displaceable compartment, derived by the simplified reference tissue model.
Time Frame
Week 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >59 years DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified Center for Epidemiological Studies Depression (CES-D) Rating Scale > 9 Decreased processing speed (defined as 0.5 SD below age-adjusted norms on the Digit Symbol Test) and decreased gait speed (defined as average walking speed over 15' course < 1 m/s) Willing and capable of providing informed consent and complying with study procedures Prefer not to be treated with a standard treatment for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy) 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 PD Mini Mental Status Exam (MMSE) < 25 HRSD ≥ 25 or the presence of significant suicide risk 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 LDOPA Acute, severe, or unstable medical or neurological illness Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, history of joint replacement surgery, or history of spine surgery Hypotension (SBP<90), hypertension (SBP >150 or DBP > 90), past stroke causing sensory or movement deficits, cardiac arrhythmias, or any other severe or uncontrolled cardiovascular disease 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) Presence of a clinically significant brain abnormality, significant anemia, insulin dependent diabetes, a history of cardiovascular disease, or uncontrolled/untreated risk factors for coronary artery disease
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
Yes
IPD Sharing Plan Description
Data obtained from this study will be shared with the National Institute of Mental Health (NIMH) Data Archive (NDA) and will maintain patient confidentiality by ensuring exclusion of all 18 identifiers (outlined by HIPAA) prior to data sharing. All assessment outcomes will be shared twice a year as per NIMH Data Archive (NDA) guidelines.
IPD Sharing Time Frame
Data will be available for as long as NIMH deems necessary.
IPD Sharing Access Criteria
Information can be accessed by going to the NUMH Data Archive website and searching the protocol. One must request access to detailed human subjects data. To do this you must be sponsored by an NIH recognized institution with a Federal wide Assurance and have a research related need to access NIMH Data Archive (NDA) data.
Citations:
PubMed Identifier
32919398
Citation
Wengler K, Ashinoff BK, Pueraro E, Cassidy CM, Horga G, Rutherford BR. Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression. Neuropsychopharmacology. 2021 Jun;46(7):1233-1239. doi: 10.1038/s41386-020-00860-z. Epub 2020 Sep 12.
Results Reference
derived
PubMed Identifier
31178096
Citation
Rutherford BR, Slifstein M, Chen C, Abi-Dargham A, Brown PJ, Wall MW, Vanegas-Arroyave N, Stern Y, Bailey V, Valente E, Roose SP. Effects of L-DOPA Monotherapy on Psychomotor Speed and [11C]Raclopride Binding in High-Risk Older Adults With Depression. Biol Psychiatry. 2019 Aug 1;86(3):221-229. doi: 10.1016/j.biopsych.2019.04.007. Epub 2019 Apr 15.
Results Reference
derived

Learn more about this trial

A Study of L-DOPA for Depression and Slowing in Older Adults

We'll reach out to this number within 24 hrs