A Study of L-DOPA for Depression and Slowing in Older Adults

NCT02744391 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 7270
• Study Type: interventional
• Target: 47
• 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 R61/R33 Phased Innovation Award 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 Not Otherwise Specified; Decreased Processing Speed; Decreased Gait Speed

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression (24 Item)

  Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The 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.

  Week 3

Secondary Outcomes (18)

• Digit Symbol Substitution Test

  Screening

• Digit Symbol Substitution Test

  Week 3

• Pattern Comparison

  Screening

• Pattern Comparison

  Week 3

• Letter Comparison

  Screening

Study Arms (1)

L-DOPA

EXPERIMENTAL

Patients will receive titration of L-DOPA from 150 mg to 450 mg.

Drug: Levodopa

Interventions

Levodopa DRUG

Also known as: L-Dopa

L-DOPA

Eligibility Criteria

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

You may qualify if:

• Age \>59 years
• DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified
• Center for Epidemiological Studies Depression (CES-D) Rating Scale \> 9
• Decreased processing speed (defined as 0.5 SD below age-adjusted norms on the Digit Symbol Test) and decreased gait speed (defined as average walking speed over 15' course \< 1 m/s)
• Willing and capable of providing informed consent and complying with study procedures
• Prefer not to be treated with a standard treatment for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy)

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 PD
• Mini Mental Status Exam (MMSE) \< 25
• HRSD ≥ 25 or the presence of significant suicide risk
• 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 LDOPA
• Acute, severe, or unstable medical or neurological illness
• Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, history of joint replacement surgery, or history of spine surgery
• Hypotension (SBP\<90), hypertension (SBP \>150 or DBP \> 90), past stroke causing sensory or movement deficits, cardiac arrhythmias, or any other severe or uncontrolled cardiovascular disease
• 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)
• Presence of a clinically significant brain abnormality, significant anemia, insulin dependent diabetes, a history of cardiovascular disease, or uncontrolled/untreated risk factors for coronary artery disease

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (2)

• Wengler K, Ashinoff BK, Pueraro E, Cassidy CM, Horga G, Rutherford BR. Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression. Neuropsychopharmacology. 2021 Jun;46(7):1233-1239. doi: 10.1038/s41386-020-00860-z. Epub 2020 Sep 12.

  PMID: 32919398 DERIVED

• Rutherford BR, Slifstein M, Chen C, Abi-Dargham A, Brown PJ, Wall MW, Vanegas-Arroyave N, Stern Y, Bailey V, Valente E, Roose SP. RETRACTED: Effects of L-DOPA Monotherapy on Psychomotor Speed and [11C]Raclopride Binding in High-Risk Older Adults With Depression. Biol Psychiatry. 2019 Aug 1;86(3):221-229. doi: 10.1016/j.biopsych.2019.04.007. Epub 2019 Apr 15.

  PMID: 31178096 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Dysthymic Disorder

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

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

Limitations and Caveats

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

Results Point of Contact

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

brr8@cumc.columbia.edu

646-774-8660

Study Officials

• Bret Rutherford, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: April 20, 2016
• Study Start: August 24, 2016
• Primary Completion: September 14, 2018
• Study Completion: November 30, 2018
• Last Updated: June 13, 2023
• Results First Posted: July 5, 2019

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available for as long as NIMH deems necessary.
• Access Criteria: Information can be accessed by going to the NUMH Data Archive website and searching the protocol. One must request access to detailed human subjects data. To do this you must be sponsored by an NIH recognized institution with a Federal wide Assurance and have a research related need to access NIMH Data Archive (NDA) data.

Locations

US (1)