Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Charité Research Organisation GmbH | OTHER |
| Boehringer Ingelheim | INDUSTRY |
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers Placebo | Placebo Comparator | placebo pill at two time points |
|
| Healthy Volunteers Amisulpride | Active Comparator | amisulpride pill at two time points |
|
| MDD Patients Placebo | Active Comparator | placebo pill at two time points |
|
| MDD Patients Amisulpride | Experimental | amisulpride pill at two time points |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amisulpride Pill | Drug | Two single low doses amisulpride (100 mg); orally |
|
| 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 |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
MDD Patients:
Inclusion:
Exclusion:
Healthy Volunteers:
Inclusion:
Exclusion:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Christian Keicher, Dr. med. | Charite University, Berlin, Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charité Research Organisation GmbH | Berlin | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38012795 | Derived | Carstens L, Popp M, Keicher C, Hertrampf R, Weigner D, Meiering MS, Luippold G, Sussmuth SD, Beckmann CF, Wunder A, Grimm S. Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder - study protocol for a randomized clinical trial. Trials. 2023 Nov 27;24(1):761. doi: 10.1186/s13063-023-07788-x. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077582 | Amisulpride |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | two doses, orally |
|
| during SID task at treatment day 2 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |