Dopamine Modulation of Motivation and Motor Function in Major Depression & Inflammation

NCT05909267 | Recruiting

• 1 other identifier: MOTIVADE
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

A large body of evidence on depression heterogeneity point to an "immunometabolic" subtype characterized by the clustering of immunometabolic dysregulations with atypical behavioral symptoms related to energy homeostasis. Motivational and motor impairments reflected by symptoms of anhedonia and psychomotor retardation in major depression are closely related to alterations in energy homeostasis, are associated with increased inflammation, and may be a direct consequence of the impact of inflammatory cytokines on the dopamine system in the brain. In the proposed project, the investigators will examine the effect of dopamine stimulation on motivation and motor function in patients with major depression and healthy controls and the role of inflammation using a double-blind, randomized, placebo-controlled, cross-over design. If successful, this study would provide crucial evidence that pharmacologic strategies that increase dopamine may effectively treat inflammation-related symptoms of anhedonia and psychomotor retardation in major depression.

Conditions

Depressive Disorder, Major

Keywords

depression; inflammation; anhedonia; psychomotor retardation

Outcome Measures

Primary Outcomes (2)

• The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT).

  The PRT, which uses a signal detection paradigm, will be used to measure response bias, the propensity to select the more rewarded response ("rich").

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

• The change in mean gait speed [m/s] after L-dopa/Carbidopa compared to placebo in the dual task.

  The dual task mean gait speed will be measured with six wearable inertial measurement units. In this dual task, participants walk at their usual speed while naming as many animals as possible.

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

Secondary Outcomes (7)

• The change in choice of the hard task after L-dopa/Carbidopa compared to placebo in the Effort Expenditure for Rewards Task (EEfRT).

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

• The change in movement time [ms] after L-dopa/Carbidopa compared to placebo in the Reaction Time Task (RTI).

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

• The change in risk propensity after L-dopa/Carbidopa compared to placebo in the Risky Decision-Making Task.

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

• Response bias (logb) in the PRT

  After administration of placebo on Day 2 or Day 3.

• Mean gait speed [m/s] in the dual task

  After administration of placebo on Day 2 or Day 3.

Other Outcomes (2)

• The change in speed and accuracy after L-dopa/Carbidopa compared to placebo in the Rapid Visual Information Processing Task (RVP).

  All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.

• Risk propensity in the Risky Decision-Making Task

  At baseline on Day 1.

Study Arms (2)

L-dopa/Carbidopa followed by placebo

EXPERIMENTAL

Participants will receive first L-dopa/Carbidopa (100/25 mg), and then placebo.

Drug: L-dopa/Carbidopa; Drug: Placebo

Placebo followed by L-dopa/Carbidopa

EXPERIMENTAL

Participants will receive first placebo, and then L-dopa/Carbidopa (100/25 mg).

Drug: L-dopa/Carbidopa; Drug: Placebo

Interventions

L-dopa/Carbidopa DRUG

Patients and healthy controls will receive one time administration of L-dopa/Carbidopa (100/25 mg).

L-dopa/Carbidopa followed by placebo; Placebo followed by L-dopa/Carbidopa

Placebo DRUG

Patients and healthy controls will receive one time administration of Placebo.

L-dopa/Carbidopa followed by placebo; Placebo followed by L-dopa/Carbidopa

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For patients with major depressive disorder:
• diagnosis of major depressive disorder according to DSM-5
• free of antidepressant medication
• For healthy participants:
• C-reactive protein (CRP): ≤ 1 mg/l
• free of antidepressant medication
• free of any current psychiatric disorder

You may not qualify if:

• diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, dementia, and current/past alcohol or drug dependence
• central nervous system diseases
• neurological diseases
• suspicious undiagnosed skin lesions or a history of melanoma
• narrow-angle or wide-angle glaucoma
• bronchial asthma
• history of peptic ulcer disease
• history of seizures
• any severe somatic disease
• current infections or chronic inflammatory diseases (e.g., rheumatic diseases, inflammatory bowel disease)
• pregnancy / breast-feeding
• class 3 obesity (body mass index of 40 or higher)
• Use of medication containing reserpine (certain antihypertensive agents), tricyclic antidepressants, bon-selective monoamine oxidase (MAO) inhibitors, antiparkinsonian drugs, sympathomimetic drugs, tetrabenazine.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Prof. Dr. Stefan M. Gold: collaborator
• Prof. Dr. Soyoung Q Park: collaborator
• Dr. Ulrike Grittner: collaborator
• Motognosis GmbH: collaborator

Study Sites (1)

Klinik für Psychiatrie und Psychotherapie

Steglitz, 12203, Germany

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Inflammation; Anhedonia; Psychomotor Disorders

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Study Officials

• Woo Ri Chae, MD MSc

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Woo Ri Chae, MD MSc

CONTACT

+49 30 450 517625; woo-ri.chae@charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 18, 2023
• Study Start: July 26, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

DE (1)