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| ID | Type | Description | Link |
|---|---|---|---|
| 4R33MH110029-03 | U.S. NIH Grant/Contract | View source |
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The project end date was reached prior to the full sample enrollment
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-DOPA Arm | Experimental | 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 |
|
| Placebo Arm | Placebo Comparator | Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-DOPA | Drug | We will be using generic sinemet 25/100 tablets in this study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks) | The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 8 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Digit Symbol Test | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. |
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Inclusion Criteria:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Bret 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, 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study. |
| FG001 | Placebo Arm | Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study. |
| 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 From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks) | The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 8 data available were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Change from Baseline to 8 Weeks |
|
Subjects were monitored over a period of 8 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 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 L-DOPA: We will be using generic sinemet 25/100 tablets in this study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for infection | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blurred vision | Eye 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 | Nov 28, 2018 | May 2, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 24, 2015 | May 2, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 28, 2018 | May 2, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D019263 | Dysthymic Disorder |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D007980 | Levodopa |
| D002230 | Carbidopa |
| C009265 | carbidopa, levodopa drug combination |
| ID | Term |
|---|---|
| D004295 | Dihydroxyphenylalanine |
| D002395 | Catecholamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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Double Blind
| Placebo Oral Tablet | Drug | 25/100 placebo tablets |
|
|
| Change from Baseline to 8 Weeks |
| Single Task Gait Speed | Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 8 Weeks |
| Inventory of Depressive Symptomatology--Self Report (IDS-SR) | The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 8 Weeks |
| Pattern Comparison Test | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 8 Weeks |
| Letter Comparison Test | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Change from Baseline to 8 Weeks |
| BG001 | Placebo Arm | Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets |
| 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 |
|
| Region of Enrollment | Number | participants |
|
| Hamilton Rating Scale for Depression (24 item) | 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. | 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 |
|
| OG001 | Placebo Arm | Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets |
|
|
| Secondary | Digit Symbol Test | The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 8 data available were analyzed. | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 8 Weeks |
|
|
|
| Secondary | Single Task Gait Speed | Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with Week 8 data available were analyzed | Posted | Mean | Standard Deviation | cm/s | Change from Baseline to 8 Weeks |
|
|
|
| Secondary | Inventory of Depressive Symptomatology--Self Report (IDS-SR) | The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with available Week 8 data were analyzed | Posted | Mean | Standard Deviation | units on a scale | Change from Baseline to 8 Weeks |
|
|
|
| Secondary | Pattern Comparison Test | This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with available Week 8 data were analyzed | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 8 Weeks |
|
|
|
| Secondary | Letter Comparison Test | Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. | Participants with available Week 8 data were analyzed | Posted | Mean | Standard Deviation | Number of items correctly completed | Change from Baseline to 8 Weeks |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 14 |
| 15 |
| EG001 | Placebo Arm | Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study. Placebo Oral Tablet: 25/100 placebo tablets | 1 | 16 | 2 | 16 | 15 | 16 |
| Death by suicide | Psychiatric disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Stomach/throat discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Increased appetite | Gastrointestinal disorders | Systematic Assessment |
|
| Weight loss | Gastrointestinal disorders | Systematic Assessment |
|
| Decreased appetite | Gastrointestinal disorders | Systematic Assessment |
|
| Diverticulitis | Gastrointestinal disorders | Systematic Assessment |
|
| Hot flashes | General disorders | Systematic Assessment |
|
| Malaise/weakness | General disorders | Systematic Assessment |
|
| Poor balance | General disorders | Systematic Assessment |
|
| Incidental MRI finding | Nervous system disorders | Systematic Assessment |
|
| Anxiety during neuroimaging | Psychiatric disorders | Systematic Assessment |
|
| Fall | General disorders | Systematic Assessment |
|
| Toe fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Neck/back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Joint/limb pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Leg/ankle swelling | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle tightness/rigidity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Numbness | Nervous system disorders | Systematic Assessment |
|
| Word finding difficulty | Nervous system disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Drowsiness | Psychiatric disorders | Systematic Assessment |
|
| Excitement | Psychiatric disorders | Systematic Assessment |
|
| Vivid dreams | Psychiatric disorders | Systematic Assessment |
|
| Irritability | Psychiatric disorders | Systematic Assessment |
|
| Forgetfulness | Psychiatric disorders | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | Systematic Assessment |
|
| Panic | Psychiatric disorders | Systematic Assessment |
|
| Increased urination | Renal and urinary disorders | Systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Systematic Assessment |
|
| Cloudy urine | Renal and urinary disorders | Systematic Assessment |
|
| Sighing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Increased sweating | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Dizziness | Vascular disorders | Systematic Assessment |
|
| Increased heart rate | Vascular disorders | Systematic Assessment |
|
| Decreased heart rate | Vascular disorders | Systematic Assessment |
|
| Abnormal heart rhythm | Vascular disorders | Systematic Assessment |
|
| Palpitations | Vascular disorders | Systematic Assessment |
|
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| D001519 |
| Behavior |
| 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 |
| D008750 | Methyldopa |
| D006834 | Hydrazines |