Clinical trial NCT03863691: Influence of Dopaminergic Blockade on Stress Responses, Motivation and Emotional Reactivity in Humans.
Official title: Influence of Partial Blockade of Dopaminergic Neurotransmission Using Amisulpride on Stress Responsivity, Motivated Behavior and Emotional Reactivity in Humans.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Participants
Keywords: dopamine antagonists
dopamine blockade
psychophysiological stress response
Maastricht acute stress test (MAST)
effort based paradigms
positivity offset theory
international affective picture system (IAPS)
Lead sponsor: Philipps University Marburg
Sponsor class: OTHER
Collaborators: name: University of Hamburg-Eppendorf
First posted: 2019-03-05
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The study aims to identify whether partial blockade of human dopamine signaling with antipsychotic drugs affects human stress responses, motivation and emotion. 84 healthy adult participants are planned to complete the study protocol.

Therefore three experiments are planned:

Experiment 1: Influence of amisulpride on human stress responses. Experiment 2: Influence of amisulpride on motivated effort. Experiment 3: Influence of amisulpride on emotion.

Detailed description: The study is a double blind, placebo controlled, randomized trial with two groups. One group will be receiving placebo (PG) and the other group will receive 300 mg amisulpride (VG). All participants are planned to complete all three experiments sequentially after drug/placebo intake.

In experiment 1 we want to test whether a medium single dosage of amisulpride (VG) changes human stress responses compared to the PG. Therefore test subjects take the medication / placebo and wait for peak plasma levels. Afterwards they undergo a standardized stress test (MAST procedure,e.g. Shilton et al., 2017) where they submerge their non-dominant hand in cold water and have to do mental arithmetic tasks. We collect ECG, cortisol and skin conductance data as well as subjective measures of the stress response.

In experiment 2 that is done after completion of experiment 1 the aim is testing whether the VG compared to the PG has an altered motivated effort. Therefore so called effort based paradigms (Reddy et al., 2015) are used. In these paradigms participants are given the option between an easy and effortless way of solving a trial that is reinforced with a small monetary reward or a harder and effortful way of trial solving that is rewarded higher. We measure how often the VG versus the PG will take the easy, low reward option over the hard, high reward option.

In experiment 3 and after the completion of experiment to the aim is it to test whether the mean intensity of visually evoked emotions in the VG is changed compared to the PG. Therefore we use a stimulus set (15 positive images, 15 negative images, 15 neutral images) out of the International Affective Picture System images to evoke emotions and plan to analyze data like in positivity offset research (detailed description in: Strauss et al, 2017).

Eligibility criteria: Inclusion Criteria:

* Common European Framework of Reference for Languages level B2 in German language.
* Consent ability for all relevant aspects of the experiment.

Exclusion Criteria:

* Amisulpride allergy.
* Allergy to other components of amisulpride / placebo capsules like lactose.
* Daily intake of other medication including contraceptives.
* Tendency to seizures.
* Diagnosis of cancer especially pheochromocytoma, prolactinoma, or breast cancer.
* Kidney dysfunction: creatinine clearance below 10 ml per minute.
* High risk for stroke or thrombosis.
* Known prolongation of the QT interval,
* Any substantial medical condition that is capable of reducing the volunteers ability to participate at the study.
* Suicidal thoughts or suicide attempts in the past or at present.
* Substantial mental disorders especially schizophrenia, bipolar disorder, drug abuse, or personality disorders.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Change in Perceived stress level from baseline to post stress period.
timeFrame: After preparation period. Before (76 min before, 22 min before, 5min before) and after the stress test (directly after, 16 min as well as 30 min after completion).
measure: Percentage of difficult trials in the balloon effort task.
timeFrame: After the cortisol response of experiment 1 is subsided and directly when experiment is 2 is completely finished. This will be approximately 121 minutes after medication / placebo intake.
measure: Percentage of difficult trials in the deck choice task.
timeFrame: After finishing the balloon effort task. This will be approximately 145 minutes after medication / placebo intake.
measure: Mean positive affect ratings in response to International Affective Picture System (IAPS) images.
timeFrame: After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.
measure: Mean negative affect ratings in response to International Affective Picture System (IAPS) images.
timeFrame: After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.
Secondary outcomes:
measure: Saliva cortisol levels.
timeFrame: After preparation period. Before (62 min before, 2 min before) and after the stress test (5, 15 and 25 min after completion).
measure: Heart rate changes and changes in heart rate variability.
timeFrame: After preparation period. Before (68 min before, 49 min before), during (the whole procedure) and after (directly after completion) the stress test.
measure: Mean arousal ratings in response to International Affective Picture System (IAPS) images.
timeFrame: After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.
Other outcomes:
Locations:
city: Marburg
country: Germany
facility: Clinical Psychology and Psychotherapy, Gutenbergstr. 18
state: Hessen
Study officials:
affiliation: Philipps-Univeristy of Marburg
name: Winfried Rief, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Billman GE, Huikuri HV, Sacha J, Trimmel K. An introduction to heart rate variability: methodological considerations and clinical applications. Front Physiol. 2015 Feb 25;6:55. doi: 10.3389/fphys.2015.00055. eCollection 2015. No abstract available.
citation: Horan WP, Reddy LF, Barch DM, Buchanan RW, Dunayevich E, Gold JM, Marder SR, Wynn JK, Young JW, Green MF. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 2-External Validity and Correlates. Schizophr Bull. 2015 Sep;41(5):1055-65. doi: 10.1093/schbul/sbv090. Epub 2015 Jul 23.
citation: Reddy LF, Horan WP, Barch DM, Buchanan RW, Dunayevich E, Gold JM, Lyons N, Marder SR, Treadway MT, Wynn JK, Young JW, Green MF. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1-Psychometric Characteristics of 5 Paradigms. Schizophr Bull. 2015 Sep;41(5):1045-54. doi: 10.1093/schbul/sbv089. Epub 2015 Jul 3.
citation: Shilton AL, Laycock R, Crewther SG. The Maastricht Acute Stress Test (MAST): Physiological and Subjective Responses in Anticipation, and Post-stress. Front Psychol. 2017 Apr 19;8:567. doi: 10.3389/fpsyg.2017.00567. eCollection 2017.
citation: Strauss GP, Frost KH, Lee BG, Gold JM. THE POSITIVITY OFFSET THEORY OF ANHEDONIA IN SCHIZOPHRENIA. Clin Psychol Sci. 2017 Mar;5(2):226-238. doi: 10.1177/2167702616674989. Epub 2017 Mar 10.