The Effect of Ketamine on Aesthetics and Role for Antidepressant Effects

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess the impact of ketamine on aesthetic perception and processing. This study assesses the role of these effects in facilitating ketamine's antidepressant properties, with a focus on anhedonia. To address this aim, 25 patients with major depressive disorder and 35 healthy controls will be assessed twice with magnetic resonance imaging, once after administration of intravenous ketamine (subanesthetic dose) and once after administration of placebo.This study has a single-center, placebo-controlled, cross-over study design. During MRI, structural, resting state, and functional imaging will be performed. Functional imaging will comprise aesthetic processing, reward, and sexual arousal paradigms. In addition, various neuropsychological scales assessing depressive symptoms, anhedonia, and aesthetic processing will be performed. Eligibility for participation will be assessed during a screening visit, a follow up visit will end study participation.

Official Title
-----------------
Unraveling the Aesthetic Mind in Anhedonia, Insights From Pharmacological Imaging of the Human Brain: A Single-blind, Randomized, Placebo-controlled Cross-over Study

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: Ketamine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: General health based on medical history and physical examination Psychiatric health based on structured clinical interview for DSM-5 (SCID) for healthy controls Major depressive episode (first or recurrent) based on structured clinical interview for DSM-5 and ICD-10 for patients Age 18 to 55 years Right-handedness (due to potential lateralization effects of lefthanded subjects) Willingness and competence to sign the informed consent form Exclusion Criteria: Current or history of neurological disease Current medical illness requiring treatment Psychiatric diagnosis for healthy individuals Psychiatric comorbidity with the exception of anxiety disorders for depressed individuals Pregnancy or current breastfeeding Current or former substance abuse Previous ketamine use in lifetime Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts Failure to comply with the study protocol or to follow the instruction of the investigating team

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine first, then placebo<br>0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study, then placebo | Drug: Ketamine<br>* 0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study<br>Drug: Placebo<br>* 0.9% NaCl<br>|
| Experimental: Placebo frist, then ketamine<br>0.9% NaCl, then ketamine | Drug: Ketamine<br>* 0.5mg/kg bodyweight (or 0.25mg/kg bodyweight) ketamine, will be determined in pilot study<br>Drug: Placebo<br>* 0.9% NaCl<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD signal assessed with fMRI during aesthetic paradigm | Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during an aesthetic processing task | Change from baseline to up to 4 weeks | 
| BOLD signal assessed with fMRI during reward paradigm | Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during a reward processing task | Change from baseline to up to 4 weeks | 
| BOLD signal assessed with fMRI during sexual arousal paradigm | Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during a sexual arousal paradigm | Change from baseline to up to 4 weeks | 
| Levels of pleasantness assessed during aesthetic fMRI task | Level of pleasantness (Numbered scale) of aesthetic stimuli during aesthetic paradigm task | Change from baseline to up to 4 weeks | 
| Number of of chills assessed during aesthetic fMRI task | Number of chills in response to aesthetic stimuli during aesthetic paradigm task | Change from baseline to up to 4 weeks | 
| BOLD signal assessed with fMRI during resting state | Difference in Blood Oxygen Level Dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) between ketamine and placebo condition during resting state | Change from baseline to up to 4 weeks |