L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults

NCT03761030 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: 77334R33MH110029-03
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder; Dysthymia; Depression

Keywords

Depressive symptoms; Cognitive problems; Antidepressant non-response; Dopamine system; Older Adults; Motor slowing

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Digit Symbol Test

  Change from Baseline to 8 Weeks

• Single Task Gait Speed

  Change from Baseline to 8 Weeks

• Inventory of Depressive Symptomatology--Self Report (IDS-SR)

  Change from Baseline to 8 Weeks

• Pattern Comparison Test

  Change from Baseline to 8 Weeks

• Letter Comparison Test

  Change from Baseline to 8 Weeks

Study Arms (2)

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

Drug: L-DOPA

Placebo Arm

PLACEBO COMPARATOR

Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.

Drug: Placebo Oral Tablet

Interventions

L-DOPA DRUG

We will be using generic sinemet 25/100 tablets in this study.

Also known as: carbidopa/levodopa (Sinemet)

L-DOPA Arm

Placebo Oral Tablet DRUG

25/100 placebo tablets

Also known as: Placebo

Placebo Arm

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Dysthymic Disorder; Depression

Interventions

Levodopa; Carbidopa; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Methyldopa; Hydrazines

Limitations and Caveats

Data collected in the trial have been presented as required but are considered unreliable.

Results Point of Contact

• Title: Dr. Bret Rutherford
• Organization: New York State Psychiatric Institute

bret.rutherford@nyspi.columbia.edu

646 774 8660

Study Officials

• Bret Rutherford, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: January 9, 2019
• Primary Completion: September 8, 2021
• Study Completion: September 8, 2021
• Last Updated: May 22, 2023
• Results First Posted: May 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)