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

NCT ID: NCT03761030

Last Updated: 2023-05-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-09
• Study Completion Date: 2021-09-08

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.

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.

Conditions

Major Depressive Disorder; Dysthymia; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

L-DOPA

Intervention Type: DRUG

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

Placebo Arm

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

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

25/100 placebo tablets

Interventions

L-DOPA

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

Intervention Type: DRUG

Placebo Oral Tablet

25/100 placebo tablets

Intervention Type: DRUG

Other Intervention Names

carbidopa/levodopa (Sinemet); Placebo

Eligibility Criteria

Inclusion Criteria

1. Aged 60 years and older

2. DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified

3. Hamilton Rating Scale for Depression (HRSD) > 15

4. 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)

5. Willing to and capable of providing informed consent and complying with study procedures

6. 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

1. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months.

2. History of or current psychosis, psychotic disorder, mania, or bipolar disorder

3. Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease (PD)

4. Mini Mental Status Exam (MMSE) < 25

5. 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.

6. Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers.

7. History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA

8. Acute, severe, or unstable medical or neurological illness

9. 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:

10. Having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures

11. History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Bret Rutherford

Associate Professor of Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bret Rutherford, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

4R33MH110029-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

7733

Identifier Type: -

Identifier Source: org_study_id