Effects of a Single Dose of Amisulpride on Functional Brain Changes

Study Overview
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Brief Summary
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This study is designed to investigate effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing and at rest in healthy volunteers (HV) and in patients with Major Depressive Disorder (MDD).

Detailed Description
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Double blind, placebo-controlled, randomized, single dose, parallel-group design The study is designed to investigate effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing and at rest. Measurement of functional brain changes will occur after a single dose of amisulpride or placebo in HV and patients with MDD. It is hypothesized that functional brain changes previously linked to reward- and motivation-related processing require dopaminergic signaling and are diminished in MDD compared to HV. In MDD, but not in HV, treatment with a single low dose (100 mg) amisulpride should increase brain activation associated with reward- and motivation-related processing. To test these hypotheses, we will implement a randomized, placebo-controlled, parallel- group design with 4 treatment arms (MDD/placebo, MDD/amisulpride, HV/placebo and HV/ amisulpride). All subjects will undergo MRI scanning sessions at Visit 3 and Visit 4. Treatment with amisulpride or matching placebo will occur 3.5 to 4 hours before the start of each scanning session. Time of treatment will be standardized across subjects. At Visit 3 and Visit 4, blood samples will be taken 30 minutes pre-dose, and 1 hour, 3.5 to 4 hours, and 4.5 to 5 hours after oral drug administration to determine target plasma levels of amisulpride. The study is composed of 4 outpatient visits: Screening, baseline and 2 scanning sessions.

Official Title
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Effects of a Single Dose of Amisulpride on Functional Brain Changes During Reward- and Motivation-related Processing

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Amisulpride Pill
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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MDD Patients: Inclusion: Male and female patients with MDD; aged 18 to 45 years Montgomery-Åsberg Depression Rating Scale (MADRS) score > 7 and <26 at screening. Exclusion: Meeting diagnostic criteria for any major psychiatric disorder (other than MDD), as determined by DSM-5 at screening. Having received prescribed medication (including antidepressants (AD)) within 14 days or fluoxetine within 90 days prior to Visit 3 (apart from the contraceptive pill). Having received psychotherapy within 14 days prior to Visit 3. Positive severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) test. Healthy Volunteers: Inclusion: Healthy aged 18 to 45 years Exclusion: Meeting diagnostic criteria for any major psychiatric disorder. A history of psychiatric or neurologic disorders. Having received prescribed medication within 14 days prior to Visit 3 (apart from the contraceptive pill). Positive SARS-CoV-2 test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Healthy Volunteers Placebo<br>placebo pill at two time points | Drug: Placebo<br>* two doses, orally<br>|
| Active Comparator: Healthy Volunteers Amisulpride<br>amisulpride pill at two time points | Drug: Amisulpride Pill<br>* Two single low doses amisulpride (100 mg); orally<br>|
| Active Comparator: MDD Patients Placebo<br>placebo pill at two time points | Drug: Placebo<br>* two doses, orally<br>|
| Experimental: MDD Patients Amisulpride<br>amisulpride pill at two time points | Drug: Amisulpride Pill<br>* Two single low doses amisulpride (100 mg); orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD fMRI parameter estimates | Blood oxygen level dependent (BOLD) fMRI parameter estimates (ß-weights within the GLM analysis) will be extracted from task-related regions of interest (average %BOLD signal change and 90th percentile thereof within ROIs) under the following task-specific contrasts: Monetary Incentive Delay (MID) task: Contrast of 'High-gain'vs. 'No-gain' condition during the task CUE period ROIs ventral striatum (including nucleus accumbens) | during MID task at treatment day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Amisulpride, Functional Brain Changes, BOLD responses