Influence of Dopaminergic Blockade on Stress Responses, Motivation and Emotional Reactivity in Humans.

NCT03863691 | Completed

• 1 other identifier: III/sja/kno FF96/2018
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (5)

• Change in Perceived stress level from baseline to post stress period.

  Before and after the stress test of experiment 1 we ask every participant for their perceived stress level. These data serve as an indicator of subjective stress responses. We analyze changes in subjective stress level compared to baseline measurements (76 min and 22 min before). Five minutes before the stress test starts we measure subjective anticipatory stress response and directly after the completion we measure post stressor responses and possible residual feelings of stress (16 minutes post completion). All measurements reflect a single time series. Stress levels are obtained with visual analogue scales ranging from 0 (no stress) to 100 points (extremely stressed).

  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).

• Percentage of difficult trials in the balloon effort task.

  In experiment 2 which is a computer task, participants can choose between an easy task with low monetary reinforcement or a hard task with higher monetary reinforcement. "Easy" means that there is a low amount of physical or cognitive effort per trial and "hard" means that there is a higher amount of physical or cognitive effort per trial. From the tasks that are described in Reddy et al (2015) the balloon effort task (physical effort) and the deck choice task (mental effort) will be used. For both tasks our software automatically obtains the percentage of difficult trials with respect to the total number of trials. Note that only a single composite score is obtained after finishing the balloon effort task.

  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.

• Percentage of difficult trials in the deck choice task.

  In experiment 2 which is a computer task, participants can choose between an easy task with low monetary reinforcement or a hard task with higher monetary reinforcement. "Easy" means that there is a low amount of physical or cognitive effort per trial and "hard" means that there is a higher amount of physical or cognitive effort per trial. From the tasks that are described in Reddy et al (2015) the balloon effort task (physical effort) and the deck choice task (mental effort) will be used. For both tasks our software automatically obtains the percentage of difficult trials with respect to the total number of trials. Note that only a single composite score is obtained after finishing the deck choice effort task.

  After finishing the balloon effort task. This will be approximately 145 minutes after medication / placebo intake.

• Mean positive affect ratings in response to International Affective Picture System (IAPS) images.

  Valence and arousal measures are collected as in Strauss et al. (2017) after presentation of IAPS pictures during experiment 3. Ratings for positive affect, negative affect and arousal ratings are obtained with a 10 point self-assessment manikin scale after the presentation of each individual picture. Note that only a single composite score for positive affect is calculated as the mean value of all evaluations following the individual pictures.

  After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.

• Mean negative affect ratings in response to International Affective Picture System (IAPS) images.

  Valence and arousal measures are collected as in Strauss et al. (2017) after presentation of IAPS pictures during experiment 3. Ratings for positive affect, negative affect and arousal ratings are obtained with a 10 point self-assessment manikin scale. Note that only a single composite score for negative affect is calculated as the mean value of all evaluations following the individual pictures.

  After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.

Secondary Outcomes (3)

• Saliva cortisol levels.

  After preparation period. Before (62 min before, 2 min before) and after the stress test (5, 15 and 25 min after completion).

• Heart rate changes and changes in heart rate variability.

  After preparation period. Before (68 min before, 49 min before), during (the whole procedure) and after (directly after completion) the stress test.

• Mean arousal ratings in response to International Affective Picture System (IAPS) images.

  After experiment 3 is finished. This will be approximately 216 minutes after medication / placebo intake.

Study Arms (2)

amisulpride group

ACTIVE COMPARATOR

300 mg of the atypical antipsychotic drug amisulpride

Drug: Amisulpride 300 MG

placebo group

PLACEBO COMPARATOR

Similar looking capsules for placebo control

Drug: Placebo oral capsule

Interventions

Amisulpride 300 MG DRUG

A single dose of 300 mg amisulpride that looks identical to placebo control capsules.

amisulpride group

Placebo oral capsule DRUG

A placebo capsule with no inert pharmacological effect. Looks identical to the amisulpride capsules.

placebo group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Philipps University Marburg: lead
• University of Hamburg-Eppendorf: collaborator

Study Sites (1)

Clinical Psychology and Psychotherapy, Gutenbergstr. 18

Marburg, Hesse, 35037, Germany

Location

Related Publications (5)

• 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.

  PMID: 25762937 BACKGROUND

• 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.

  PMID: 26209546 BACKGROUND

• 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.

  PMID: 26142081 BACKGROUND

• 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.

  PMID: 28469586 BACKGROUND

• 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.

  PMID: 28497008 BACKGROUND

MeSH Terms

Interventions

Amisulpride

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Winfried Rief, Professor

  Philipps-Univeristy of Marburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: randomized, double blind, placebo controlled, between subjects design
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: March 5, 2019
• Study Start: April 15, 2019
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: September 21, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)