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

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05909267

Collaborator

Prof. Dr. Stefan M. Gold (Other), Prof. Dr. Soyoung Q Park (Other), Dr. Ulrike Grittner (Other), Motognosis GmbH (Other)

165

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: L-dopa/Carbidopa Drug: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

165 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT). [All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.]
The PRT, which uses a signal detection paradigm, will be used to measure response bias, the propensity to select the more rewarded response ("rich").
The change in mean gait speed [m/s] after L-dopa/Carbidopa compared to placebo in the dual task. [All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.]
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.

Secondary Outcome Measures

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 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.
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 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.
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.]
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.
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

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.]
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).
Risk propensity in the Risky Decision-Making Task [At baseline on Day 1.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.