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Completed

NCT Number: NCT05347199

Effects of a Single Dose of Amisulpride on Functional Brain Changes

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).

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Charité Research Organisation GmbH

Berlin, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Amisulpride Pill

Drug

Two single low doses amisulpride (100 mg); orally

Placebo

Drug

two doses, orally

Primary outcomes

  1. BOLD fMRI parameter estimates

    Time frame: during MID task at treatment day 1

    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)

Other outcomes

  1. Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during SID

    Time frame: during SID task at treatment day 2

    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

  2. Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during intstrumental learning task

    Time frame: during instrumental learning task at treatment day 1

    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

  3. Exploratory endpoint: average %BOLD signal change and 90th percentile thereof within ROIs during effort-based decision making task

    Time frame: during effort-based decision making task at treatment day 2

    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

  4. Exploratory endpoint: reaction times in ms

    Time frame: during all tasks at treatment day 1 and day 2

    Reaction times in ms extracted from the in- scanner protocol log files

  5. Exploratory endpoint: response accuracy in percent

    Time frame: during all tasks at treatment day 1 and day 2

    Estimates of response accuracy extracted from the in- scanner protocol log files

  6. Exploratory endpoint:average %BOLD signal change and 90th percentile thereof within ROIs during resting state

    Time frame: during resting state at treatment day 1

    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)

  7. Exploratory endpoint: Arterial Spin Labeling (ASL)

    Time frame: during asl at treatment day 1

    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

  8. Exploratory endpoint (Correlation between BOLD signal and self-reported anhedonia )

    Time frame: treatment day 1 and treatment day 2

    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

  9. Exploratory endpoint (Correlation between BOLD signal and behavioral measures)

    Time frame: treatment day 1 and treatment day 2

    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

  10. Exploratory endpoint (Correlation between functional connectivity and self-reported anhedonia)

    Time frame: treatment day 1 and treatment day 2

    Correlation between resting state functional connectivity and self- reported anhedonia after amisulpride administration as compared to placebo in MDD patients relative to HV

  11. Exploratory endpoint (Correlation between functional connectivity and behavioral measures)

    Time frame: treatment day 1 and treatment day 2

    Correlation between resting state functional connectivity and behavioral measures after amisulpride administration as compared to placebo in MDD patients relative to HV

  12. Exploratory endpoint (Change in plasma levels of amisulpride)

    Time frame: treatment day 1 and treatment day 2

    Changes in plasma levels of amisulpride including correlation to changes in BOLD signal in MDD patients relative to HV

  13. Exploratory endpoint (Change in whole brain BOLD signal)

    Time frame: treatment day 1 and treatment day 2

    Changes in whole brain BOLD signal after amisulpride administration as compared to placebo in MDD patients relative to HV

Sponsors and collaborators

Lead sponsor

Simone Grimm

Other

Collaborators

  • Boehringer Ingelheim
  • Charité Research Organisation GmbH

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Apr 26, 2022
Registry last updated
Nov 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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