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

Effects of Pharmacological Dopamine Modulation on Motivation and Motor Function in Major Depression Characterized by Low-grade Inflammation.

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.

Study Overview

• Status: Recruiting
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: L-dopa/Carbidopa; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Woo Ri Chae, MD MSc; Phone Number: +49 30 450 517625; Email: woo-ri.chae@charite.de

Study Locations

• Germany
  • Berlin-Steglitz, Germany, 12203
    • Recruiting
    • Klinik für Psychiatrie und Psychotherapie
    • Contact: Woo Ri Chae, MD MSc; Phone Number: 030 450 517625; Email: motivade-studie@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For patients with major depressive disorder:

• diagnosis of major depressive disorder according to DSM-5
• C-reactive protein (CRP): > 3 mg/l or ≤ 1 mg/l
• free of antidepressant medication

For healthy participants:

• C-reactive protein (CRP): ≤ 1 mg/l
• free of antidepressant medication
• free of any current psychiatric disorder

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-dopa/Carbidopa followed by placebo; Participants will receive first L-dopa/Carbidopa (100/25 mg), and then placebo.	Drug: L-dopa/Carbidopa; Patients and healthy controls will receive one time administration of L-dopa/Carbidopa (100/25 mg).; Drug: Placebo; Patients and healthy controls will receive one time administration of Placebo.
Experimental: Placebo followed by L-dopa/Carbidopa; Participants will receive first placebo, and then L-dopa/Carbidopa (100/25 mg).	Drug: L-dopa/Carbidopa; Patients and healthy controls will receive one time administration of L-dopa/Carbidopa (100/25 mg).; Drug: Placebo; Patients and healthy controls will receive one time administration of Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in choice of the hard task after L-dopa/Carbidopa compared to placebo in the Effort Expenditure for Rewards Task (EEfRT).	The EEfRT, a widely used, multi-trial task in which participants are given an opportunity on each trial to choose between two different task difficulty levels in order to obtain monetary rewards, will be used as an objective measure of reward motivation. The EEfRT is reported as the percent of high effort (hard) trials selected. A higher percentage reflects higher motivation for effort expenditure.	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).	The RTI from the Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess movement time, which is the time taken to touch the stimulus on the computer screen after the press pad had been released.	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.	In the Risky Decision-Making Task, participants have to make choices between a risky option and a safe alternative. Risk Propensity, the proportion of risk-taking trials, will be a secondary outcome.	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.
Choice of the hard task in the EEfRT		After administration of placebo on Day 2 or Day 3.
Movement time [ms] in the RTI		After administration of placebo on Day 2 or Day 3.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in speed and accuracy after L-dopa/Carbidopa compared to placebo in the Rapid Visual Information Processing Task (RVP).	The RVP from the Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess performance speed (mean latency for correct responses) and accuracy (target sensitivity score).	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.

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Prof. Dr. Stefan M. Gold; Prof. Dr. Soyoung Q Park; Dr. Ulrike Grittner; Motognosis GmbH
• Investigators: Principal Investigator: Woo Ri Chae, MD MSc, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: June 11, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: depression; inflammation; anhedonia; psychomotor retardation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Inflammation; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Carbidopa
• Other Study ID Numbers: MOTIVADE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No