Clinical trial NCT05347199: Effects of a Single Dose of Amisulpride on Functional Brain Changes
Official title: Effects of a Single Dose of Amisulpride on Functional Brain Changes During Reward- and Motivation-related Processing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
Amisulpride
Functional Brain Changes
BOLD responses
Lead sponsor: Medical School Berlin
Sponsor class: OTHER
Collaborators: name: Charité Research Organisation GmbH
name: Boehringer Ingelheim
First posted: 2022-04-26
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: BOLD fMRI parameter estimates
timeFrame: during MID task at treatment day 1
Secondary outcomes:
Other outcomes:
measure: Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during SID
timeFrame: during SID task at treatment day 2
measure: Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during intstrumental learning task
timeFrame: during instrumental learning task at treatment day 1
measure: Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during effort-based decision making task
timeFrame: during effort-based decision making task at treatment day 2
measure: Exploratory endpoint: reaction times in ms
timeFrame: during all tasks at treatment day 1 and day 2
measure: Exploratory endpoint: response accuracy in percent
timeFrame: during all tasks at treatment day 1 and day 2
measure: Exploratory endpoint:average %BOLD signal change and 90th percentile thereof within ROIs during resting state
timeFrame: during resting state at treatment day 1
measure: Exploratory endpoint: Arterial Spin Labeling (ASL)
timeFrame: during asl at treatment day 1
measure: Exploratory endpoint (Correlation between BOLD signal and self-reported anhedonia )
timeFrame: treatment day 1 and treatment day 2
measure: Exploratory endpoint (Correlation between BOLD signal and behavioral measures)
timeFrame: treatment day 1 and treatment day 2
measure: Exploratory endpoint (Correlation between functional connectivity and self-reported anhedonia)
timeFrame: treatment day 1 and treatment day 2
measure: Exploratory endpoint (Correlation between functional connectivity and behavioral measures)
timeFrame: treatment day 1 and treatment day 2
measure: Exploratory endpoint (Change in plasma levels of amisulpride)
timeFrame: treatment day 1 and treatment day 2
measure: Exploratory endpoint (Change in whole brain BOLD signal)
timeFrame: treatment day 1 and treatment day 2
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
Study officials:
affiliation: Charite University, Berlin, Germany
name: Christian Keicher, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: