Clinical trial NCT05909267: Dopamine Modulation of Motivation and Motor Function in Major Depression & Inflammation
Official title: Effects of Pharmacological Dopamine Modulation on Motivation and Motor Function in Major Depression Characterized by Low-grade Inflammation.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depressive Disorder, Major
Keywords: depression
inflammation
anhedonia
psychomotor retardation
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Prof. Dr. Stefan M. Gold
name: Prof. Dr. Soyoung Q Park
name: Dr. Ulrike Grittner
name: Motognosis GmbH
First posted: 2023-06-18
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

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

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.

Primary outcomes:
measure: The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT).
timeFrame: All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.
measure: The change in mean gait speed [m/s] after L-dopa/Carbidopa compared to placebo in the dual task.
timeFrame: 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:
measure: The change in choice of the hard task after L-dopa/Carbidopa compared to placebo in the Effort Expenditure for Rewards Task (EEfRT).
timeFrame: All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.
measure: The change in movement time [ms] after L-dopa/Carbidopa compared to placebo in the Reaction Time Task (RTI).
timeFrame: All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.
measure: The change in risk propensity after L-dopa/Carbidopa compared to placebo in the Risky Decision-Making Task.
timeFrame: All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.
measure: Response bias (logb) in the PRT
timeFrame: After administration of placebo on Day 2 or Day 3.
measure: Mean gait speed [m/s] in the dual task
timeFrame: After administration of placebo on Day 2 or Day 3.
measure: Choice of the hard task in the EEfRT
timeFrame: After administration of placebo on Day 2 or Day 3.
measure: Movement time [ms] in the RTI
timeFrame: After administration of placebo on Day 2 or Day 3.
Other outcomes:
measure: The change in speed and accuracy after L-dopa/Carbidopa compared to placebo in the Rapid Visual Information Processing Task (RVP).
timeFrame: All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo.
measure: Risk propensity in the Risky Decision-Making Task
timeFrame: At baseline on Day 1.
Locations:
city: Berlin-Steglitz
country: Germany
facility: Klinik für Psychiatrie und Psychotherapie
Study officials:
affiliation: Charite University, Berlin, Germany
name: Woo Ri Chae, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: