- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03761030
L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
May 18, 2023 updated by: Bret Rutherford, New York State Psychiatric Institute
Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
Enrolled participants were aged 60 and older with (1) a DSM 5 depressive disorder, (2) significant depressive symptoms, and (3) decreased thinking or walking speed will receive 8 weeks of treatment with L-DOPA up to 450mg.
We will test whether L-DOPA increases brain dopamine release using neuroimaging and whether it speeds up thinking and walking speed.
Data collected in the proposed studies may help identify a new treatment for LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD.
This project also will elucidate the neurobiology of slowing at molecular, structural, and functional levels of analysis, increasing our understanding of the interplay between these aging-associated processes and the pathophysiologic changes underlying late life neuropsychiatric disorders.
Exploring patient characteristics that predict response to L-DOPA may provide useful information to guide differential therapeutics and develop personalized medicine for LLD.
Study Type
Interventional
Enrollment (Actual)
51
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
New York, New York, United States, 10032
- New York State Psychiatric Institute
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
60 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Aged 60 years and older
- DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified
- Hamilton Rating Scale for Depression (HRSD) > 15
- Decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed (defined as average walking speed over 15' course < 1m/s)
- Willing to and capable of providing informed consent and complying with study procedures
- Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy) have been discussed and the individual agrees to be involved in an experimental treatment.
Exclusion Criteria:
- Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months.
- History of or current psychosis, psychotic disorder, mania, or bipolar disorder
- Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease (PD)
- Mini Mental Status Exam (MMSE) < 25
- HRSD ≥ 28; HRSD suicide item > 2 or the presence of significant suicide risk as judged by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline.
- Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers.
- History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA
- Acute, severe, or unstable medical or neurological illness
Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, mobility limiting history of joint replacement surgery, or history of spine surgery
FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY:
- Having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures
- History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: L-DOPA Arm
Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks.
Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose
|
We will be using generic sinemet 25/100 tablets in this study.
Other Names:
|
Placebo Comparator: Placebo Arm
Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.
|
25/100 placebo tablets
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)
Time Frame: Change from Baseline to 8 Weeks
|
The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery.
Total scores range from 0-74, not including atypical symptoms sub-scale.
A score of 16 or above is typically considered to indicate the presence of depressive symptoms.
Higher scores indicate greater severity.
Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
|
Change from Baseline to 8 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Digit Symbol Test
Time Frame: Change from Baseline to 8 Weeks
|
The Digit Symbol test is a neuropsychological test measuring information processing speed.
It consists of digit-symbol pairs (e.g.
1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits.
Under each digit the subject should write down the corresponding symbol as fast as possible.
The number of correct symbols within the allowed time is measured.
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 8 Weeks
|
Single Task Gait Speed
Time Frame: Change from Baseline to 8 Weeks
|
Patients' gait was assessed as walking speed in cm/s on a 15' walking course.
Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects).
Two trials were completed, and gait speed was based on the average of 2 trials.
Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
|
Change from Baseline to 8 Weeks
|
Inventory of Depressive Symptomatology--Self Report (IDS-SR)
Time Frame: Change from Baseline to 8 Weeks
|
The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder.
The scale ranges from 0-84 with higher scores indicating more severe depression.
Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.
|
Change from Baseline to 8 Weeks
|
Pattern Comparison Test
Time Frame: Change from Baseline to 8 Weeks
|
This test required participants to identify whether two visual patterns are the "same" or "not the same" (responses were made by pressing a "yes" or "no" button).
Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many.
Scores 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
Time Frame: Change from Baseline to 8 Weeks
|
Subjects were asked to determine whether two strings of letters are the same or different.
There are 3 pages and the subject is given 30 seconds per page.
Scoring is based on the number answered correctly.
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Bret Rutherford, MD, New York State Psychiatric Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 9, 2019
Primary Completion (Actual)
September 8, 2021
Study Completion (Actual)
September 8, 2021
Study Registration Dates
First Submitted
November 29, 2018
First Submitted That Met QC Criteria
November 29, 2018
First Posted (Actual)
December 3, 2018
Study Record Updates
Last Update Posted (Actual)
May 22, 2023
Last Update Submitted That Met QC Criteria
May 18, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Dysthymic 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
- 7733
- 4R33MH110029-03 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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 PsychiatryActive, not recruitingDepression | 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
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
Clinical Trials on L-DOPA
-
Impel PharmaceuticalsCompletedParkinson's DiseaseAustralia
-
Children's Hospital of PhiladelphiaAvailableInsulinoma | Beckwith-Wiedemann Syndrome | Congenital Hyperinsulinism (CHI)United States
-
GlaxoSmithKlineCompletedParkinson DiseaseUnited States, Korea, Republic of, Estonia, Russian Federation, Slovakia, Argentina, Chile
-
Assistance Publique - Hôpitaux de ParisTerminatedThyroid Carcinoma | Thyroid Neoplasm | Medullary CarcinomaFrance
-
Children's Hospital of PhiladelphiaUniversity of PennsylvaniaCompletedHyperinsulinism | Congenital Hyperinsulinism | Persistent Hyperinsulinemic Hypoglycemia of Infancy | CHI | PHHIUnited States
-
Molecular NeuroImagingCompletedParkinson's Disease
-
Rion Inc.ProPharmaActive, not recruiting
-
Biotie Therapies Inc.CompletedParkinson's DiseaseUkraine, Argentina, Romania, Canada, United States, Chile
-
Merck Sharp & Dohme LLCCompletedBrain Diseases | Central Nervous System Diseases | Parkinson Disease | Movement Disorders | Neurodegenerative Diseases
-
PfizerVicuron PharmaceuticalsCompleted