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

Depressive Disorder, Major Clinical Trial

— MOTIVADE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05909267
• Other study ID #: MOTIVADE
• Status: Recruiting
• Phase: N/A
• Start date: July 26, 2023
• Est. completion date: October 2025

Study information

• Verified date: August 2023
• Source: Charite University, Berlin, Germany
• Contact: Woo Ri Chae, MD MSc
• Phone: +49 30 450 517625
• Email: woo-ri.chae[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 165
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Inflammation

Intervention

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

Locations

Country	Name	City	State
Germany	Klinik für Psychiatrie und Psychotherapie	Berlin-Steglitz

Sponsors (5)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Dr. Ulrike Grittner, Motognosis GmbH, Prof. Dr. Soyoung Q Park, Prof. Dr. Stefan M. Gold

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	Risk propensity in the Risky Decision-Making Task		At baseline on Day 1.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	Response bias (logb) in the PRT		After administration of placebo on Day 2 or Day 3.
Secondary	Mean gait speed [m/s] in the dual task		After administration of placebo on Day 2 or Day 3.
Secondary	Choice of the hard task in the EEfRT		After administration of placebo on Day 2 or Day 3.
Secondary	Movement time [ms] in the RTI		After administration of placebo on Day 2 or Day 3.