Measuring Psychomotor Response to L-DOPA Challenge As a Biomarker for Outcomes in Late-Life Depression: a Pilot Feasibility Trial

NCT ID: NCT06626152

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-15
• Study Completion Date: 2026-05-30

Brief Summary

Background

Adults over the age of 60 with symptoms of major depressive disorder are said to have late-life depression (LLD), a condition that usually decreases a person's quality of life and is associated with other risks like physical frailty and dementia. A common feature of more severe LLD is psychomotor slowing, where a person's ability to think and move are impaired. For example, they might not be able to walk or process information as quickly, and they might have problems with their working memory.

Psychomotor slowing in LLD might be the result of a problem with the way a person's body produces or responds to the neurotransmitter dopamine. The drug Levodopa (L-DOPA), which can replace missing dopamine in the brain, has been used to treat to treat Parkinson's disease for many decades, and it might also affect psychomotor slowing in LLD.

Methods

In this study, participants are adults aged 60 years or older with moderate to severe major depression. Participants undergo the "L-DOPA challenge"-a 2-week period where they receive a dose of L-DOPA once a day for the first week and a dose of L-DOPA twice a day for the second week. Before and after a participant completes the L-DOPA challenge, the study team assesses their depressive symptoms and psychomotor function. After the L-DOPA challenge, if a participant still shows signs of moderate or severe depression, they receive an antidepressant for 12 weeks.

Aims

The first aim of this study is to test the feasibility of the L-DOPA challenge-that is, whether most of the 50 participants recruited for this study will complete the L-DOPA challenge. For example, participants might have to withdraw if they can't make the daily visits to the research site to receive their L-DOPA medication, if they can't tolerate the medication's side effects, or if their depressive symptoms get significantly worse. Our hypothesis is that 80% of the participants will complete the L-DOPA challenge.

The second aim of the study is to see if L-DOPA affects participants' depressive symptoms, processing speed, and working memory. Our hypothesis is that L-DOPA response, measured as an improvement in gait speed, is associated with a decrease in depressive symptoms and an increase in processing speed and working memory.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

L-DOPA Challenge

Participants will be administered a levodopa-carbidopa challenge, at a dosage of 150mg/37.5mg once daily for one week, followed by twice daily for one week. Psychomotor speed will be assessed before and after the challenge.

Group Type: EXPERIMENTAL

Apo-levocarb

Intervention Type: DRUG

As above.

Interventions

Apo-levocarb

As above.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Outpatient persons capable of providing informed consent
• Minimum age of 60 years old
• MINI International Neuropsychiatric Interview diagnosis of major depressive disorder, based on DSM-5 criteria
• MADRS score of ≥15 (moderate/severe depression)
• On stable doses of psychotropic medication, including antidepressant medication, for at least 4 weeks
• Able to adhere to the intervention schedule

Exclusion Criteria

• Current diagnosis of major neurocognitive disorder
• Current active psychosis
• Unstable medical illness, including clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease
• Diagnosis of narrow angle glaucoma
• Suspicious, undiagnosed skin lesions or a history of melanoma
• History of myocardial infarction
• Atrial, nodal, or ventricular arrhythmias
• History of seizures or seizure disorder
• History of peptic ulcer disease
• History of allergy or other hypersensitivity to levodopa, carbidopa, or to any other ingredient in the formulation of Levocarb
• Active suicidal ideation
• Psychotropic medication initiation or dose change <4 weeks prior to enrolment
• Regular use of dopamine antagonist or benzodiazepines ≥2mg lorazepam equivalent per day
• Unable to complete neuropsychological testing in the English language
• Have a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete the neuropsychological tests)
• History of falls, with ≥1 fall per week during the past 4 weeks

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

Sponsors

Providence Health & Services

OTHER

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Kevin Smith

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Nicholas J Ainsworth, MD

Role: CONTACT

nainsworth@providencehealth.bc.ca

6048069090

Facility Contacts

Nicholas J Ainsworth, MD

Role: primary

nainsworth@providencehealth.bc.ca

6048069090

Other Identifiers

LLDOPA

Identifier Type: -

Identifier Source: org_study_id