- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04493320
1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- New York State Psychiatric Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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
- 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
Exclusion Criteria:
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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
150-450mg carbidopa/levodopa 3 times daily
Other Names:
Carbidopa/levodopa-matched placebo tablet 3 times daily
Other Names:
|
Experimental: 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. |
150-450mg carbidopa/levodopa 3 times daily
Other Names:
Carbidopa/levodopa-matched placebo tablet 3 times daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 from Baseline to 3 weeks (post Step 1)
|
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 from Baseline to 3 weeks (post Step 1)
|
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 from Week 3 to Week 7 (post-Step 2)
|
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 from Baseline to 3 weeks (post Step 1)
|
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 from Week 3 to Week 7 (post-Step 2)
|
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 from Baseline to 3 weeks (post Step 1)
|
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 from Week 3 to Week 7 (post-Step 2)
|
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 from Baseline to 3 weeks (post Step 1)
|
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.
|
Change from Week 3 to Week 7 (post-Step 2)
|
[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.
|
Baseline (prior to LDOPA or placebo administration)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Montgomery Asberg Depression Rating Scale Following Step 1
Time Frame: Change from Baseline to 3 weeks (post 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.
|
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)
|
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
Time Frame: Change from Baseline to 3 weeks (post 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
Time Frame: Change from Week 4 to Week 7 (post-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)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Bret R Rutherford, MD, New York State Psychiatric Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Immunologic Factors
- Dopamine Agonists
- Dopamine Agents
- Adjuvants, Immunologic
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Aromatic Amino Acid Decarboxylase Inhibitors
- Levodopa
- Carbidopa
- Carbidopa, levodopa drug combination
Other Study ID Numbers
- 7976
- R01MH123660-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
Kintsugi Mindful Wellness, Inc.Sonar Strategies; Vituity PsychiatryRecruitingDepression | Depression Moderate | Depression Severe | Depression MildUnited States
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
Clinical Trials on Carbidopa/levodopa
-
University of MinnesotaNot yet recruitingIdiopathic Parkinson DiseaseUnited States
-
AbbVie (prior sponsor, Abbott)Completed
-
NeuroDerm Ltd.Quotient ClinicalCompletedParkinson's DiseaseUnited Kingdom
-
Snyder, Robert W., M.D., Ph.D., P.C.WithdrawnAge-related Macular DegenerationUnited States
-
Centre for Addiction and Mental HealthCompleted
-
Novartis PharmaceuticalsWithdrawn
-
Academisch Medisch Centrum - Universiteit van Amsterdam...ZonMw: The Netherlands Organisation for Health Research and DevelopmentCompleted
-
Novartis PharmaceuticalsOrion Corporation, Orion PharmaCompletedParkinson's DiseaseUnited States, Switzerland, Germany, Finland, Greece, Italy, Spain, United Kingdom, Canada, France, Turkey, Belgium, Sweden, Austria
-
NovartisTerminated
-
Orion Corporation, Orion PharmaCompletedParkinson's DiseaseFinland, Germany, Hungary, Latvia