Trial Outcomes & Findings for A Study of L-DOPA for Depression and Slowing in Older Adults (NCT NCT02744391)

NCT ID: NCT02744391

Last Updated: 2023-06-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 47 participants
• Primary outcome timeframe: Week 3
• Results posted on: 2023-06-13

Participant Flow

Participant milestones

Measure	L-DOPA Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Overall Study STARTED	47
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Measure	L-DOPA Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Overall Study Lost to Follow-up	9
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	3

Baseline Characteristics

47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

Baseline characteristics by cohort

Measure	L-DOPA n=47 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Age, Categorical <=18 years	0 Participants n=47 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=47 Participants
Age, Categorical >=65 years	42 Participants n=47 Participants
Sex: Female, Male Female	30 Participants n=47 Participants
Sex: Female, Male Male	17 Participants n=47 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=47 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=47 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=47 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=47 Participants
Race (NIH/OMB) Asian	1 Participants n=47 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=47 Participants
Race (NIH/OMB) Black or African American	17 Participants n=47 Participants
Race (NIH/OMB) White	26 Participants n=47 Participants
Race (NIH/OMB) More than one race	0 Participants n=47 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=47 Participants
Region of Enrollment United States	47 Participants n=47 Participants
Hamilton Rating Scale for Depression (24 item)	15.53 Units on a scale STANDARD_DEVIATION 6.04 • n=36 Participants • 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

PRIMARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Hamilton Rating Scale for Depression (24 Item)	10.94 Units on a Scale Standard Deviation 6.87

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Digit Symbol Substitution Test	31.86 total score Standard Deviation 9.69

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Digit Symbol Substitution Test	41.42 total score Standard Deviation 9.56

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Pattern Comparison	24.72 total score Standard Deviation 5.42

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Pattern Comparison	27.61 total score Standard Deviation 4.95

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Letter Comparison	14.36 Total Correct Standard Deviation 4.73

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Letter Comparison	15.69 Total Correct Standard Deviation 4.54

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Single Task Gait Speed	0.80 m/s Standard Deviation 0.18

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Single Task Gait Speed	.92 m/s Standard Deviation .21

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Dual Task Gait Speed	0.69 m/s Standard Deviation .23

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Dual Task Gait Speed	0.82 m/s Standard Deviation .24

SECONDARY outcome

Timeframe: Screening

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Inventory of Depressive Symptomatology-Self Report	26.42 total score Standard Deviation 12.57

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=36 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Inventory of Depressive Symptomatology-Self Report	15.09 total score Standard Deviation 10.64

SECONDARY outcome

Timeframe: Baseline

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Pre-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum	2.43 mCi/ ml Standard Deviation 0.25

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis. Only 10 subjects were scanned in this study.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Post-Treatment [11C]-Raclopride Binding Potential: Sensorimotor Striatum	2.19 mCi/ ml Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis. Only 10 subjects were scanned in this study.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Pre-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum	2.04 mCi/ ml Standard Deviation 0.18

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis. Only 10 subjects were scanned in this study.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Post-Treatment [11C]-Raclopride Binding Potential: Limbic Striatum	2.04 mCi/ ml Standard Deviation 0.15

SECONDARY outcome

Timeframe: Baseline

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis. Only 10 subjects were scanned in this study.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Pre-Treatment [11C]-Raclopride Binding Potential: Associative Striatum	2.17 mCi/ ml Standard Deviation 0.26

SECONDARY outcome

Timeframe: Week 3

Population: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis. Only 10 subjects were scanned in this study.

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.

Outcome measures

Measure	L-DOPA n=10 Participants Patients will receive titration of L-DOPA from 150 mg to 450 mg. Levodopa
Post-Treatment [11C]-Raclopride Binding Potential: Associative Striatum	2.05 mCi/ ml Standard Deviation 0.26

Adverse Events

L-DOPA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Bret R. Rutherford

New York State Psychiatric Institute

Phone: 646-774-8660

Email: brr8@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place