History of Changes for Study: NCT03761030

L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults

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Study Record Versions

Version	Submitted Date	Changes
1	November 29, 2018	None (earliest Version on record)
2	November 30, 2018	Outcome Measures and Study Status
3	January 15, 2019	Recruitment Status, Study Status, Study Identification, Oversight, Contacts/Locations and Study Design
4	February 5, 2019	Study Status
5	January 28, 2020	Study Status
6	March 5, 2020	Contacts/Locations, Study Status and Eligibility
7	April 15, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Design
8	April 16, 2020	Recruitment Status and Study Status
9	June 18, 2020	Arms and Interventions, Eligibility, Study Design, Study Status, Study Description, Oversight and Sponsor/Collaborators
10	July 27, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Design
11	April 16, 2021	Study Status
12	January 26, 2022	Recruitment Status, Study Status and Contacts/Locations
13	May 2, 2023	Quality Control Review has not concluded Returned: May 16, 2023 Recruitment Status, Study Status, Outcome Measures, Contacts/Locations, Study Design, Document Section and Study Description
14	May 17, 2023	Quality Control Review has not concluded Returned: May 18, 2023 Outcome Measures, Document Section, Baseline Characteristics and Study Status
15	May 18, 2023	Study Status, Outcome Measures

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	7733
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
Secondary IDs:	4R33MH110029-03 [U.S. NIH Grant/Contract]

Study Status


Record Verification:	May 2023
Overall Status:	Terminated [The project end date was reached prior to the full sample enrollment]
Study Start:	January 9, 2019
Primary Completion:	September 8, 2021 [Actual]
Study Completion:	September 8, 2021 [Actual]

First Submitted:	November 29, 2018
First Submitted that Met QC Criteria:	November 29, 2018
First Posted:	December 3, 2018 [Actual]

Last Update Submitted that Met QC Criteria:
Last Update Posted:	May 17, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	New York State Psychiatric Institute
Responsible Party:	Principal Investigator Investigator: Bret Rutherford Official Title: Associate Professor of Clinical Psychiatry Affiliation: New York State Psychiatric Institute
Collaborators:	National Institute of Mental Health (NIMH)

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

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.

Conditions


Conditions:	Major Depressive Disorder Dysthymia Depression
Keywords:	Depressive symptoms Cognitive problems Antidepressant non-response Dopamine system Older Adults Motor slowing

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 4
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	51 [Actual]

Arms and Interventions

Arms

Assigned Interventions

Experimental: L-DOPA Arm

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

Drug: L-DOPA

We will be using generic sinemet 25/100 tablets in this study.

Other Names:

carbidopa/levodopa (Sinemet)

Placebo Comparator: Placebo Arm

Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.

Drug: Placebo Oral Tablet

25/100 placebo tablets

Other Names:

Placebo

Outcome Measures

[See Results Section.]


Primary Outcome Measures:
1.	Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks) [ Time Frame: Change from Baseline to 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:
1.	Digit Symbol Test [ Time Frame: Change from Baseline to 8 Weeks ] 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. 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.
Quality Control Review Comment provided by the National Library of Medicine: The description of the scale or categories does not include sufficient information to understand the results reported.
2.	Single Task Gait Speed [ Time Frame: Change from Baseline to 8 Weeks ] 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.
3.	Inventory of Depressive Symptomatology--Self Report (IDS-SR) [ Time Frame: Change from Baseline to 8 Weeks ] 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.
4.	Pattern Comparison Test [ Time Frame: Change from Baseline to 8 Weeks ] 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. 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.
Quality Control Review Comment provided by the National Library of Medicine: The description of the scale or categories does not include sufficient information to understand the results reported.
5.	Letter Comparison Test [ Time Frame: Change from Baseline to 8 Weeks ] 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. 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.
Quality Control Review Comment provided by the National Library of Medicine: The description of the scale or categories does not include sufficient information to understand the results reported.

Eligibility


Minimum Age:	60 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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)

Contacts/Locations


Study Officials:	Bret Rutherford, MD Principal Investigator New York State Psychiatric Institute
Locations:	United States, New York
	New York State Psychiatric Institute New York, New York, United States, 10032

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information:

Document Section


	Study Protocol Document Date: November 28, 2018 Uploaded: 05/02/2023 09:35 File Name: Prot_000.pdf
	Statistical Analysis Plan Document Date: July 24, 2015 Uploaded: 05/02/2023 09:36 File Name: SAP_001.pdf
	Informed Consent Form Document Date: November 23, 2018 Uploaded: 05/02/2023 09:36 File Name: ICF_002.pdf

Participant Flow

Recruitment Details

Pre-assignment Details

In total, 51 subjects were enrolled. Of the 51 enrolled, 20 subjects were found to be ineligible or did not continue in the study after enrolling. Thus, 51 participants enrolled and 31 were assigned to a treatment group and began the study.

Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets

Period Title: Overall Study
Started	15	16
Completed	13	12
Not Completed	2	4

Baseline Characteristics

Arm/Group Title

L-DOPA Arm

Placebo Arm

Total

Arm/Group Description

L-DOPA: We will be using generic sinemet 25/100 tablets in this study.

Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.

Placebo Oral Tablet: 25/100 placebo tablets

Total of all reporting groups

Overall Number of Baseline Participants

Baseline Analysis Population Description

[Not Specified]

Age, Continuous

Mean (Standard Deviation)
Unit of measure: years

Number Analyzed

15 Participants

16 Participants

31 Participants

69.0(7.3)

66.7(6.1)

67.8(6.7)

Sex: Female, Male

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

15 Participants

16 Participants

31 Participants

Female

60%

62.5%

61.29%

Male

40%

37.5%

38.71%

Ethnicity (NIH/OMB)

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

15 Participants

16 Participants

31 Participants

Hispanic or Latino

6.67%

25%

16.13%

Not Hispanic or Latino

86.67%

68.75%

77.42%

Unknown or Not Reported

6.67%

6.25%

6.45%

Race (NIH/OMB)

Measure Type: Count of Participants
Unit of measure: Participants

Number Analyzed

15 Participants

16 Participants

31 Participants

American Indian or Alaska Native

Asian

6.25%

3.23%

Native Hawaiian or Other Pacific Islander

Black or African American

26.67%

18.75%

22.58%

White

60%

62.5%

61.29%

More than one race

13.33%

12.5%

12.9%

Unknown or Not Reported

Region of Enrollment

Measure Type: Number
Unit of measure: participants

Number Analyzed

15 Participants

16 Participants

31 Participants

United States

Hamilton Rating Scale for Depression (24 item)^[1]

Mean (Standard Deviation)
Unit of measure: units on a scale

Number Analyzed

15 Participants

16 Participants

31 Participants

21.1(4.7)

20.3(3.9)

20.7(4.3)

[1]

Measure 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.

Clinical Global Impressions--Severity

Mean (Standard Deviation)
Unit of measure: units on a scale

Number Analyzed

15 Participants

16 Participants

31 Participants

3.7(0.6)

4.3(0.7)

4.0(0.7)

Quality Control Review Comment provided by the National Library of Medicine:

The description of the scale or categories does not include sufficient information to understand the results reported.

Outcome Measures

1. Primary Outcome:

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

Outcome Measure Data

Analysis Population Description

Participants with Week 8 data available were analyzed.


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	12	13
Mean (Standard Deviation) Unit of Measure: units on a scale	-2.2(6.4)	-3.6(5.8)

2. Secondary Outcome:

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. 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

Quality Control Review Comment provided by the National Library of Medicine:

The description of the scale or categories does not include sufficient information to understand the results reported.

Outcome Measure Data

Analysis Population Description

Participants with Week 8 data available were analyzed.


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	9	10
Mean (Standard Deviation) Unit of Measure: units on a scale	2.8(4.0)	5.0(3.5)

3. Secondary Outcome:

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

Outcome Measure Data

Analysis Population Description

Participants with Week 8 data available were analyzed


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	10	9
Mean (Standard Deviation) Unit of Measure: units on a scale	3.7(14.9)	-3.8(14.7)

Quality Control Review Comment provided by the National Library of Medicine:

The Unit of Measure appears inconsistent with the Measure Title, the Measure Description, or both.

4. Secondary Outcome:

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

Outcome Measure Data

Analysis Population Description

Participants with available Week 8 data were analyzed


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation) Unit of Measure: units on a scale	-9.8(7.1)	-12.1(15.0)

5. Secondary Outcome:

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 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. 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

Quality Control Review Comment provided by the National Library of Medicine:

The description of the scale or categories does not include sufficient information to understand the results reported.

Outcome Measure Data

Analysis Population Description

Participants with available Week 8 data were analyzed


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	11	10
Mean (Standard Deviation) Unit of Measure: units on a scale	0.6(2.1)	1.2(2.3)

6. Secondary Outcome:

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. 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

Quality Control Review Comment provided by the National Library of Medicine:

The description of the scale or categories does not include sufficient information to understand the results reported.

Outcome Measure Data

Analysis Population Description

Participants with available Week 8 data were analyzed


Arm/Group Title	L-DOPA Arm	Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.	Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
Overall Number of Participants Analyzed	11	10
Mean (Standard Deviation) Unit of Measure: units on a scale	1.2(1.6)	0.7(1.4)

Adverse Events


Time Frame	Subjects were monitored over a period of 8 weeks.
Adverse Event Reporting Description	[Not specified]

Arm/Group Title	L-DOPA Arm		Placebo Arm
Arm/Group 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study.		Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets
All-Cause Mortality
	L-DOPA Arm		Placebo Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	0 / 15 (0%)		1 / 16 (6.25%)
Serious Adverse Events
	L-DOPA Arm		Placebo Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	0 / 15 (0%)		2 / 16 (12.5%)
Infections and infestations
Hospitalization for infection ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Psychiatric disorders
Death by suicide ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
†Indicates events were collected by systematic assessment.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	L-DOPA Arm		Placebo Arm
	Affected / At Risk (%)	# Events	Affected / At Risk (%)	# Events
Total	14 / 15 (93.33%)		15 / 16 (93.75%)
Eye disorders
Blurred vision ^†	2 / 15 (13.33%)	2	2 / 16 (12.5%)	2
Gastrointestinal disorders
Constipation ^†	2 / 15 (13.33%)	2	2 / 16 (12.5%)	3
Decreased appetite ^†	0 / 15 (0%)	0	4 / 16 (25%)	4
Diarrhea ^†	3 / 15 (20%)	3	2 / 16 (12.5%)	2
Diverticulitis ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Dry mouth ^†	5 / 15 (33.33%)	5	4 / 16 (25%)	4
Increased appetite ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Nausea ^†	5 / 15 (33.33%)	8	3 / 16 (18.75%)	3
Stomach/throat discomfort ^†	2 / 15 (13.33%)	2	1 / 16 (6.25%)	1
Weight loss ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
General disorders
Fall ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Hot flashes ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Malaise/weakness ^†	1 / 15 (6.67%)	1	2 / 16 (12.5%)	2
Poor balance ^†	1 / 15 (6.67%)	1	1 / 16 (6.25%)	1
Musculoskeletal and connective tissue disorders
Bursitis ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Joint/limb pain ^†	4 / 15 (26.67%)	4	0 / 16 (0%)	0
Leg/ankle swelling ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Muscle tightness/rigidity ^†	1 / 15 (6.67%)	1	3 / 16 (18.75%)	3
Neck/back pain ^†	5 / 15 (33.33%)	6	1 / 16 (6.25%)	1
Toe fracture ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Nervous system disorders
Headache ^†	4 / 15 (26.67%)	4	5 / 16 (31.25%)	5
Incidental MRI finding ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Numbness ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Word finding difficulty ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Psychiatric disorders
Anxiety during neuroimaging ^†	0 / 15 (0%)	0	2 / 16 (12.5%)	2
Drowsiness ^†	5 / 15 (33.33%)	6	2 / 16 (12.5%)	2
Excitement ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Forgetfulness ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Insomnia ^†	6 / 15 (40%)	7	6 / 16 (37.5%)	7
Irritability ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Panic ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Suicidal ideation ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Vivid dreams ^†	1 / 15 (6.67%)	1	3 / 16 (18.75%)	3
Renal and urinary disorders
Cloudy urine ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Increased urination ^†	2 / 15 (13.33%)	2	1 / 16 (6.25%)	1
Urinary tract infection ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hyperventilation ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Nasal congestion ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Sighing ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Skin and subcutaneous tissue disorders
Increased sweating ^†	0 / 15 (0%)	0	1 / 16 (6.25%)	1
Itching ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Vascular disorders
Abnormal heart rhythm ^†	1 / 15 (6.67%)	1	0 / 16 (0%)	0
Decreased heart rate ^†	1 / 15 (6.67%)	1	1 / 16 (6.25%)	1
Dizziness ^†	6 / 15 (40%)	6	4 / 16 (25%)	4
Increased heart rate ^†	2 / 15 (13.33%)	2	0 / 16 (0%)	0
Palpitations ^†	0 / 15 (0%)	0	2 / 16 (12.5%)	2
†Indicates events were collected by systematic assessment.

Limitations and Caveats


Data collected in the trial have been presented as required but are considered unreliable.

More Information


Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study. There is NOT an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact:
Name/Official Title:	Dr. Bret Rutherford
Organization:	New York State Psychiatric Institute
Phone:	646 774 8660
Email:	bret.rutherford@nyspi.columbia.edu