Effects of a Single Dose of Amisulpride on Functional Brain Changes

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05347199
• Other study ID #: MSB-C002
• Status: Completed
• Phase: Phase 1
• Start date: May 17, 2022
• Est. completion date: September 25, 2023

Study information

• Verified date: November 2023
• Source: Medical School Berlin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: September 25, 2023
• Est. primary completion date: September 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Amisulpride Pill
Two single low doses amisulpride (100 mg); orally
• Placebo
two doses, orally

Locations

Country	Name	City	State
Germany	Charité Research Organisation GmbH	Berlin

Sponsors (3)

Lead Sponsor	Collaborator
Simone Grimm	Boehringer Ingelheim, Charité Research Organisation GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during SID	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: Social Incentive Delay (SID) task: Contrast of 'High-gain' vs. 'No-gain' condition during the task CUE period ROIs: ventral striatum (including nucelues accumbens), ventral tegmental area, dorsal anterior cingulate cortex, insula, ventromedial prefrontal cortex/ orbitofrontal cortex and ventral pallidum	during SID task at treatment day 2
Other	Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during intstrumental learning task	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: Instrumental Learning task: Contrast of the Gain-cue vs. neutral cue conditions during the task cue and feedback periods; ROIs: ventral striatum (including nucelues accumbens), ventral tegmental area, dorsal anterior cingulate cortex, insula, ventromedial prefrontal cortex/ orbitofrontal cortex and ventral pallidum	during instrumental learning task at treatment day 1
Other	Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during effort-based decision making task	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: Effort-based Decision Making task: Contrast of the High reward vs. Low reward conditions during the task CUE2 period Contrast of the High effort vs. Low effort conditions during the task CUE2 period; ROIs: ventral striatum (including nucelues accumbens), ventral tegmental area, dorsal anterior cingulate cortex, insula, ventromedial prefrontal cortex/ orbitofrontal cortex and ventral pallidum	during effort-based decision making task at treatment day 2
Other	Exploratory endpoint: reaction times in ms	Reaction times in ms extracted from the in- scanner protocol log files	during all tasks at treatment day 1 and day 2
Other	Exploratory endpoint: response accuracy in percent	Estimates of response accuracy extracted from the in- scanner protocol log files	during all tasks at treatment day 1 and day 2
Other	Exploratory endpoint:average %BOLD signal change and 90th percentile thereof within ROIs during resting state	Blood oxygen level dependent (BOLD) fMRI signal magnitude and BOLD signal standard deviation during Resting State within the following a-priori defined regions: Default Mode Network (posterior cingulate, vmPFC and medial temporal lobe), Central Executive Network (dorsolateral prefrontal cortex, premotor cortex, precuneus), and Salience Network Network (amygdala, insula and dorsal anterior cingulate)	during resting state at treatment day 1
Other	Exploratory endpoint: Arterial Spin Labeling (ASL)	Changes in relative and absolute cerebral blood flow measured through Arterial Spin Labelling MR in whole brain and in the following brain regions: (bilateral): ventral striatum, ventromedial prefrontal cortex/ orbitofrontal cortex, ventral tegmental area, dorsal anterior cingulate cortex, insula, and ventral pallidum after amisulpride administration	during asl at treatment day 1
Other	Exploratory endpoint (Correlation between BOLD signal and self-reported anhedonia )	Correlation between magnitude of BOLD signal during reward-and motivation-related processing and self-reported anhedonia after amisulpride administration as compared to placebo in MDD patients relative to HV	treatment day 1 and treatment day 2
Other	Exploratory endpoint (Correlation between BOLD signal and behavioral measures)	Correlation between magnitude of BOLD signal during reward-and motivation-related processing and behavioral measures after amisulpride administration as compared to placebo in MDD patients relative to HV	treatment day 1 and treatment day 2
Other	Exploratory endpoint (Correlation between functional connectivity and self-reported anhedonia)	Correlation between resting state functional connectivity and self- reported anhedonia after amisulpride administration as compared to placebo in MDD patients relative to HV	treatment day 1 and treatment day 2
Other	Exploratory endpoint (Correlation between functional connectivity and behavioral measures)	Correlation between resting state functional connectivity and behavioral measures after amisulpride administration as compared to placebo in MDD patients relative to HV	treatment day 1 and treatment day 2
Other	Exploratory endpoint (Change in plasma levels of amisulpride)	Changes in plasma levels of amisulpride including correlation to changes in BOLD signal in MDD patients relative to HV	treatment day 1 and treatment day 2
Other	Exploratory endpoint (Change in whole brain BOLD signal)	Changes in whole brain BOLD signal after amisulpride administration as compared to placebo in MDD patients relative to HV	treatment day 1 and treatment day 2
Primary	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