Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing

NCT04650217 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: 80651K24MH122514-01A1
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In this new research study, 80 adults aged \> 60 years with a significant depressive disorder and slowed processing and/or gait speed will be randomized to receive levodopa (L-DOPA; which the Candidate has previously shown to increase psychomotor speed and decrease depressive symptoms in older adults), aerobic exercise (itself an effective antidepressant treatment as monotherapy), or their combination in a 2x2 design incorporating placebo and a stretching/toning control. Participants will be evaluated before and after this 12-week duration study across cognitive domains, psychiatric symptoms, gait kinematics and mobility, and task-based magnetic resonance imaging (MRI) focused on effort-based decision making and reward processing. Data from this study will contribute toward the development of improved treatment and prevention strategies to maximize the functioning and active healthspan of older adults with neuropsychiatric disorders.

Conditions

Depressive Disorder

Keywords

slowed Information processing speed; slowed gait speed

Outcome Measures

Primary Outcomes (1)

• Montgomery Asberg Depression Rating Scale (MADRS)

  The MADRS is a standard rater-administered measure of depression severity that will be used to measure changes in depressive symptoms during the study. The total MADRS score ranges from a minimum score of 0 to a maximum score of 60. Higher scores indicate more severe depression.

  Week 0 (Baseline)

Study Arms (4)

L-DOPA + Exercise

ACTIVE COMPARATOR

N=20 subjects assigned to L-DOPA + Exercise will receive L-DOPA three times daily for up to 450mg (L-DOPA) and also will receive exercise training 4 times a week (exercise)

Drug: Carbidopa/levodopa; Behavioral: Exercise training

LDOPA + Control

ACTIVE COMPARATOR

N=20 subjects assigned to L-DOPA + Control will receive L-DOPA three times daily for up to 450mg (L-DOPA) and also will receive a stretching and toning regime (Control).

Drug: Carbidopa/levodopa; Behavioral: Control

Placebo + Exercise

PLACEBO COMPARATOR

N=20 subjects assigned to Placebo + Exercise will receive placebo three times daily and also will receive exercise training 4 times a week (exercise).

Drug: Placebo; Behavioral: Exercise training

Placebo + Control

PLACEBO COMPARATOR

N=20 subjects assigned to Placebo + Control will receive placebo three times daily and also will receive a stretching and toning regime (Control).

Drug: Placebo; Behavioral: Control

Interventions

Carbidopa/levodopa DRUG

L-DOPA is the immediate precursor of dopamine, is converted to dopamine in presynaptic dopaminergic nerve terminals, and enhances dopaminergic transmission in multiple brain regions. Subjects assigned to L-DOPA will begin with a Week 1 L-DOPA daily dosage of 150mg, or 1.5 25mg carbidopa/100mg levodopa tablets at 9am and placebo tablets at 1pm and 5pm. In Week 2 the L-DOPA daily dose will increase to 300mg (1.5 25mg carbidopa/100mg levodopa tablets at 9am and 5pm, with placebo at 1pm), followed by a Week 3 to 8 L-DOPA daily dose of 450mg (1.5 25mg carbidopa/100mg levodopa tablets three times daily). Subjects assigned to placebo will take 1.5 placebo tablets three times daily for three weeks. Individuals will be instructed to maintain the same timing of doses throughout the study. Individuals unable to tolerate an increased dose will have their dosage reduced to the maximum previously tolerated dose.

Also known as: sinemet

L-DOPA + Exercise; LDOPA + Control

Placebo DRUG

Carbidopa/levodopa matched placebo

Also known as: Placebo tablet

Placebo + Control; Placebo + Exercise

Exercise training BEHAVIORAL

Subjects assigned t Exercise will exercise individually at their home on a program set each week by Dr. Sloan and the research assistant (RA) coach, who will work with the patient to ensure they train according to the program at the appropriate level of intensity. Subjects will select from a series of aerobic activities and for Weeks 1-2 will train at 55-65 percent of maximum HR as established during their qualifying CPET. In Weeks 3-4, they will increase exercise intensity to 65-75 percent of maximum HR, and in Weeks 5-12 they will train at 75 percent of maximum HR.

Also known as: lifestyle counseling, psychotherapy

L-DOPA + Exercise; Placebo + Exercise

Control BEHAVIORAL

Control will engage in a series of stretches and toning exercises designed to promote flexibility and improve core strength.

LDOPA + Control; Placebo + Control

Eligibility Criteria

• Age: 60 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged greater than or equal to 60 years
• Diagnostic and Statistical Manual (DSM) 5 MDD, Dysthymia, or Depression Not Otherwise Specified (NOS)
• Hamilton Rating Scale for Depression (HRSD) greater than or equal to 18
• Decreased processing speed (defined as 1 SD below age-adjusted norms on the Digit Symbol Test) or decreased gait speed (defined as average walking speed over 15' course less than 1m/s)
• Willing to and capable of providing informed consent and complying with study procedures

You may not qualify if:

• Substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months
• History of psychosis, psychotic disorder, mania, or bipolar disorder
• Probable Alzheimer's Disease, Vascular Dementia, or Parkinson's disease
• Mini Mental Status Examination (MMSE) less than or equal to 24
• HRSD suicide item greater than 2 or Clinical Global Impressions (CGI) Severity score of 7 at baseline
• Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, or mood stabilizers
• History of allergy, hypersensitivity reaction, or severe intolerance to levodopa/carbidopa
• Any physical or intellectual disability adversely affecting ability to complete assessments, including physical inability to perform treadmill testing and exercise protocol
• 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
• Contraindication to magnetic resonance imaging

Sponsors & Collaborators

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

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Depressive Disorder

Interventions

carbidopa, levodopa drug combination; Exercise; Psychotherapy

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Behavioral Disciplines and Activities

Results Point of Contact

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

brr8@cumc.columbia.edu

646 774 8660

Study Officials

• Bret R 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Psychiatry

Model Details: Double-Blind

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: December 2, 2020
• Study Start: October 7, 2021
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 2, 2023
• Results First Posted: February 2, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)