DepressionPhase 4NCT04493320
1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
A Phase 4 study testing Carbidopa/levodopa in people with Depression and Cognitive Impairment, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Depression, Cognitive Impairment, Gait Impairment
- What is being tested?
- Carbidopa/levodopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2021to 27 Oct 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Depressed Subjects:
- Age 60 years or older (female subjects will be post-menopausal by virtue of their age, but last menstrual period month and year will be documented in the study database)
- Diagnosis and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD)
- Montgomery Asberg Depression Rating Scale Score (MADRS) >=15
- Decreased processing speed or decreased gait speed
- Capable of providing informed consent and complying with study procedures
Show all 11Show fewer
- Alternative standard treatments for MDD or PDD have been discussed and the individual agrees to be involved in an experimental treatment
- Psychiatrically Healthy Elders:
- Age 60 years or older years old
- MADRS < 8
- Capable of providing informed consent and complying with study procedures
Who cannot join
- Depressed Subjects:
- Diagnosis of Substance Use Disorder (excluding Tobacco Use Disorder) in the past 12 months
- History of psychosis (except brief psychosis associated with transient medical conditions [e.g., delirium, urinary tract infection, etc], psychotic disorder, mania, or bipolar disorder.
- Primary neurological disorder, including dementia, stroke, Parkinson's disease, or epilepsy.
- Mini Mental State Examination (MMSE) < 24
- MADRS suicide item >4 or other indication of acute suicidality
Show all 18Show fewer
- Current or recent (within the past 2 weeks) treatment with antidepressants, antipsychotics, or mood stabilizers
- History of hypersensitivity, allergy, or intolerance to L-DOPA
- Any physical or intellectual disability adversely affecting ability to complete assessments.
- Acute, severe, or unstable medical illness
- Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, or history of joint replacement or spine surgery that limits mobility
- Contraindication to MRI scanning (Metal implants, pacemaker, metal prostheses, metal orthodontic appliances in the body unless there is confirmation that the substance is MRI compatible.)
- History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)
- Has a medical condition managed with medication and/or device and the managing physician considers the condition and/or its management a contraindication to the research use of L-DOPA in this participant
- Psychiatrically Healthy Elders:
- Any personal history of DSM-5 disorder
- Family history of MDD in first-degree relative
- Plus, Exclusion criteria 8-12 above
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
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).
Read the detailed description
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.
- Conditions
- Depression, Cognitive Impairment, Gait Impairment
- Being tested
- Carbidopa/levodopa, Placebo
- Medical subject headings
- Depression, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbidopa/levodopaDrug
Also called L-DOPA, Sinemet
150-450mg carbidopa/levodopa 3 times daily
PlaceboDrug
Also called Placebo tablet
Carbidopa/levodopa-matched placebo tablet 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Carbidopa/levodopa; Drug: Placebo |
| 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. Receives: Drug: Carbidopa/levodopa; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (prior to LDOPA or placebo administration)
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from Week 4 to Week 7 (post-Step 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study start10 Feb 2021
- Primary completion27 Oct 2021
- Study completion27 Oct 2021
Why it stopped: Study terminated by sponsor (NIMH)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind crossover study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Vanderbilt University Medical Center, Columbia University, Emory University
- Responsible party
- Principal investigator, Bret Rutherford, New York State Psychiatric Institute
- Investigators
- Bret R Rutherford, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04493320
- Sponsor's protocol ID
- 7976
- Other IDs
- R01MH123660-01
- Status last verified
- May 2023
- First submitted
- 27 Jul 2020
- Last updated
- 22 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
- ClinicalTrials.gov ID
- NCT04493320
- Acronym / sponsor ID
- 7976
- Conditions
- Depression, Cognitive Impairment, Gait Impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated by sponsor (NIMH)
- Enrolment
- 5 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Vanderbilt University Medical Center, Columbia University, Emory University
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 27 Oct 2021 (actual)
- Study completion
- 27 Oct 2021 (actual)
- First posted
- 30 Jul 2020 (actual)
- Results
- Posted 22 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind crossover study
| Arm | Type | Receives |
|---|---|---|
| L-DOPA, Then Placebo | Experimental | Drug: Carbidopa/levodopa, Drug: PlaceboStep 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 | Drug: Carbidopa/levodopa, Drug: PlaceboStep 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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 60 years or older (female subjects will be post-menopausal by virtue of their age, but last menstrual period month and year will be documented in the study database)
- Diagnosis and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD)
- Montgomery Asberg Depression Rating Scale Score (MADRS) >=15
- Decreased processing speed or decreased gait speed
- Capable of providing informed consent and complying with study procedures
Key exclusion criteria (18 listed)
- Diagnosis of Substance Use Disorder (excluding Tobacco Use Disorder) in the past 12 months
- History of psychosis (except brief psychosis associated with transient medical conditions [e.g., delirium, urinary tract infection, etc], psychotic disorder, mania, or bipolar disorder.
- Primary neurological disorder, including dementia, stroke, Parkinson's disease, or epilepsy.
- Mini Mental State Examination (MMSE) < 24
- MADRS suicide item >4 or other indication of acute suicidality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carbidopa/levodopaAlso: L-DOPA, Sinemet150-450mg carbidopa/levodopa 3 times daily | Drug | L-DOPA, Then Placebo, Placebo, Then L-DOPA |
| PlaceboAlso: Placebo tabletCarbidopa/levodopa-matched placebo tablet 3 times daily | Drug | L-DOPA, Then Placebo, Placebo, Then L-DOPA |
Primary outcome
Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1
Time frame: Change from Baseline to 3 weeks (post 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 in Digit Symbol Test Following Step 1
Time frame: Change from Baseline to 3 weeks (post 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 in Digit Symbol Test Following Step 2
Time frame: Change from Week 3 to Week 7 (post-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.
Change in Pattern Comparison Test Following Step 1
Time frame: Change from Baseline to 3 weeks (post 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 in Pattern Comparison Test Following Step 2
Time frame: Change from Week 3 to Week 7 (post-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 in Letter Comparison Test Following Step 1
Time frame: Change from Baseline to 3 weeks (post 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 in Letter Comparison Test Following Step 2
Time frame: Change from Week 3 to Week 7 (post-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 in Single Task Gait Speed Test Following Step 1
Time frame: Change from Baseline to 3 weeks (post 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 in Single Task Gait Speed Test Following Step 2
Time frame: Change from Week 3 to Week 7 (post-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.
[18F]-FDOPA PET Measure in Striatal Region of Interest
Time frame: Baseline (prior to LDOPA or placebo administration)
[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.
4 secondary outcomes
Change in Montgomery Asberg Depression Rating Scale Following Step 1
Time frame: Change from Baseline to 3 weeks (post Step 1)
Change in Montgomery Asberg Depression Rating Scale Following Step 2
Time frame: Change from Week 4 to Week 7 (post-Step 2)
Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 1
Time frame: Change from Baseline to 3 weeks (post Step 1)
Change in Quick Inventory for Depressive Symptomatology (QIDS) Following Step 2
Time frame: Change from Week 4 to Week 7 (post-Step 2)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Improving Student Mental Health Through a Universal Trauma-Informed Intervention
Anxiety Symptoms, Post-traumatic Stress Symptoms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bret R Rutherford, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carbidopa/levodopa in people with Depression and Cognitive Impairment, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Effort Expenditure for Rewards Task (EEfRT) Following Step 1 (time frame: Change from Baseline to 3 weeks (post Step 1)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2023.