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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH123660-01 | U.S. NIH Grant/Contract | View source |
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Study terminated by sponsor (NIMH)
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
| Vanderbilt University Medical Center | OTHER |
| Columbia University | OTHER |
| Emory University |
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Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is common, predicts poor outcomes, and manifests as difficulties in motivation and effort along with cognitive and gait impairment. While studies of dopamine function in early and midlife depression primarily focus on individuals' ability to feel pleasure and respond to rewards, they often exclude the cognitive and physical function domains relevant for older adults despite a recognized decline in dopamine function with normal aging. The objectives of this collaborative R01 proposal between Columbia University/New York State Psychiatric Institute and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to stimulation with carbidopa/levodopa (L-DOPA).
Supported by pilot data, this project builds on past work demonstrating that dopamine function declines with aging, that dopaminergic dysfunction contributes to deficits in behavior, and that L-DOPA administration improves cognitive and motor performance. The long-term goal of this line of research is to determine how dopaminergic dysfunction contributes to clinical presentations of LLD, how responsive behavioral symptoms are to modulation of dopamine function, and to identify novel targets for future interventions. Investigator's approach is to enroll 30 psychiatrically healthy elders and 60 depressed elders at Columbia/NYSPI exhibiting either slowed processing speed or slowed gait speed. Participants will undergo thorough clinical evaluations and complete PET imaging measuring different aspects of the brain's dopamine system, neuromelanin-sensitive MRI measurement of longterm dopamine transmission, functional MRI focused on effort-based decision making and reward processing, a comprehensive neurocognitive evaluation, a physical performance evaluation, and measurement of inflammatory markers. To assess responsivity of the dopamine system to modulation, depressed subjects then will be randomized to L-DOPA or placebo for 3 weeks, followed by repeat multimodal MRI and cognitive/behavioral assessments. In a second phase, participants will receive the opposite intervention for an additional 3 weeks followed by clinical and cognitive assessments only. This proposal is significant and innovative, as no prior published study has comprehensively examined dopamine-dependent behaviors in LLD. This will inform treatment approaches focusing on facilitating cognition and movement, reducing the effort cost of voluntary behavior, and promoting behavioral activation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-DOPA, Then Placebo | Experimental | Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1 week taper period. Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. |
|
| Placebo, Then L-DOPA | Experimental | Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1-week taper period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carbidopa/levodopa | Drug | 150-450mg carbidopa/levodopa 3 times daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1 | In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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. This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Digit Symbol Test Following Step 1 | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Digit Symbol Test Following Step 2 | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Montgomery Asberg Depression Rating Scale Following Step 1 | Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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. |
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Inclusion Criteria:
Depressed Subjects:
Psychiatrically Healthy Elders:
Exclusion Criteria:
Depressed Subjects:
Psychiatrically Healthy Elders:
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| Name | Affiliation | Role |
|---|---|---|
| Bret R Rutherford, MD | New York State Psychiatric Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York State Psychiatric Institute | New York | New York | 10032 | United States |
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In total, 5 depressed subjects were enrolled. Of the 5 enrolled, 1 subject was found to be ineligible. Thus, 5 participants enrolled and 4 were assigned to a treatment group and began the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | L-DOPA, Then Placebo | Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1 week taper period. Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
| FG001 | Placebo, Then L-DOPA | Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | L-DOPA, Then Placebo | Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1 week taper period. Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1 | In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. 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. This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | percentage of high effort choices | Change from Baseline to 3 weeks (post Step 1) |
Subjects were monitored over a period of 7 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L-DOPA | This trial entailed the administration of either L-DOPA or placebo in Step 1, followed by crossover to the other treatment assignment in Step 2 (i.e., L-DOPA followed by placebo or placebo followed by L-DOPA). Adverse events are grouped here by treatment assignment (L-DOPA or placebo). This arm pertains to the administration of L-DOPA in Step 1 and Step 2 of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
Data collected in the trial have been presented as required but are considered unreliable.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bret Rutherford | New York State Psychiatric Institute | 646 774 8660 | bret.rutherford@nyspi.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 24, 2020 | May 4, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 3, 2019 | May 4, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 24, 2020 | May 4, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
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Not provided
| ID | Term |
|---|---|
| C009265 | carbidopa, levodopa drug combination |
| D007980 | Levodopa |
| ID | Term |
|---|---|
| D004295 | Dihydroxyphenylalanine |
| D002395 | Catecholamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
Not provided
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| OTHER |
Double blind crossover study
Not provided
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| Placebo | Drug | Carbidopa/levodopa-matched placebo tablet 3 times daily |
|
|
| Change from Week 3 to Week 7 (post-Step 2) |
| Change in Pattern Comparison Test Following Step 1 | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Pattern Comparison Test Following Step 2 | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Week 3 to Week 7 (post-Step 2) |
| Change in Letter Comparison Test Following Step 1 | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Letter Comparison Test Following Step 2 | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Week 3 to Week 7 (post-Step 2) |
| Change in Single Task Gait Speed Test Following Step 1 | 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. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Single Task Gait Speed Test Following Step 2 | 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. | Change from Week 3 to Week 7 (post-Step 2) |
| [18F]-FDOPA PET Measure in Striatal Region of Interest | [18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the "reference region" to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity. | Baseline (prior to LDOPA or placebo administration) |
| Change from Baseline to 3 weeks (post Step 1) |
| Change in Montgomery Asberg Depression Rating Scale Following Step 2 | Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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. | Change from Week 4 to Week 7 (post-Step 2) |
| Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1 | QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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. | Change from Baseline to 3 weeks (post Step 1) |
| Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2 | QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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. | Change from Week 4 to Week 7 (post-Step 2) |
| BG001 | Placebo, Then L-DOPA | Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Montgomery Asberg Depression Rating Scale | Mean | Standard Deviation | units on a scale |
|
| Clinical Global Impressions--Severity | The Clinical Global Impressions--Severity (CGI-S) scale measures the clinician's assessment of global illness severity. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher scores denote more severe illness. | Mean | Standard Deviation | units on a scale |
|
| Quick Inventory for Depressive Symptomatology | Mean | Standard Deviation | units on a scale |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | L-DOPA, Then Placebo | Step 1 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1 week taper period. Step 2 (3 Weeks): Participants will receive L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
| OG001 | Placebo, Then L-DOPA | Step 1 (3 Weeks): Participants will receive 3 L-DOPA matching placebo tablets daily. Participants will then enter a 1-week taper period. Step 2 (3 Weeks): Participants will first receive 150 mg of L-DOPA daily in Week 1, 300 mg of L-DOPA in Week 2, and 450 mg L-DOPA in Week 3. Participants will then enter a 1-week taper period. Carbidopa/levodopa: 150-450mg carbidopa/levodopa 3 times daily Placebo: Carbidopa/levodopa-matched placebo tablet 3 times daily |
|
|
| Primary | Change in Digit Symbol Test Following Step 1 | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Primary | Change in Digit Symbol Test Following Step 2 | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 3 and Week 7 data available were analyzed | Posted | Number | Number of items correctly completed | Change from Week 3 to Week 7 (post-Step 2) |
|
|
|
| Primary | Change in Pattern Comparison Test Following Step 1 | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Primary | Change in Pattern Comparison Test Following Step 2 | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 3 and Week 7 data available were analyzed | Posted | Number | Number of items correctly completed | Change from Week 3 to Week 7 (post-Step 2) |
|
|
|
| Primary | Change in Letter Comparison Test Following Step 1 | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Primary | Change in Letter Comparison Test Following Step 2 | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 3 and Week 7 data available were analyzed | Posted | Number | Number of items correctly completed | Change from Week 3 to Week 7 (post-Step 2) |
|
|
|
| Primary | Change in Single Task Gait Speed Test Following Step 1 | 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. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | cm/s | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Primary | Change in Single Task Gait Speed Test Following Step 2 | 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. | Participants with Week 3 and Week 7 data available were analyzed | Posted | Number | cm/s | Change from Week 3 to Week 7 (post-Step 2) |
|
|
|
| Primary | [18F]-FDOPA PET Measure in Striatal Region of Interest | [18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the "reference region" to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity. | Participants who had a baseline [18F]-FDOPA PET scan | Posted | Number | min^-1 | Baseline (prior to LDOPA or placebo administration) |
|
|
|
| Secondary | Change in Montgomery Asberg Depression Rating Scale Following Step 1 | Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression 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. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | units on a scale | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Secondary | Change in Montgomery Asberg Depression Rating Scale Following Step 2 | Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. 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. | Participants with Week 4 and Week 7 data available were analyzed | Posted | Number | units on a scale | Change from Week 4 to Week 7 (post-Step 2) |
|
|
|
| Secondary | Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1 | QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of 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. | Participants with Baseline and Week 3 data available were analyzed | Posted | Mean | Standard Deviation | units on a scale | Change from Baseline to 3 weeks (post Step 1) |
|
|
|
| Secondary | Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2 | QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. 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. | Posted | Number | units on a scale | Change from Week 4 to Week 7 (post-Step 2) |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Placebo | This trial entailed the administration of either L-DOPA or placebo in Step 1, followed by crossover to the other treatment assignment in Step 2 (i.e., L-DOPA followed by placebo or placebo followed by L-DOPA). Adverse events are grouped here by treatment assignment (L-DOPA or placebo). This arm pertains to the administration of placebo in Step 1 and Step 2 of the study. | 0 | 3 | 0 | 3 | 2 | 3 |
| Headache | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Dizziness | Vascular disorders | Systematic Assessment |
|
| Increased blood pressure | Vascular disorders | Systematic Assessment |
|
| Faintness | General disorders | Systematic Assessment |
|
| Drowsiness | Psychiatric disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
Not provided
| D001523 |
| Mental Disorders |
| D002396 |
| Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014443 | Tyrosine |