NCT04359147

Brief Summary

Incidental affective states, i.e., affective states can influence decision making and selective attention to threatening information. Acute stress is such an affective state and is a powerful contextual modulator of decision-making processes and selective attention to threat. In terms of physiological and neurohormonal changes, the stress response has been well characterized: Exposure to stress elicits an array of autonomic, endocrine, and behavioral responses. The physiological stress response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus noradrenergic (LC-NA) system with cortisol and norepinephrine (NE) as their end products. There is compelling evidence that the stress hormones cortisol and NE influence cognitive processes. However, only very few studies so far used pharmacological approaches to specify the role of stress neuromodulators on decision making and selective attention to threat and these studies are hardly comparable due to differences in the experimental design, e.g., the decision making task used. Furthermore, the neural underpinnings of stress effects on decision making and selective attention to threat are uninvestigated so far. The aim of the proposed project is to clarify the role of the major stress neuromodulators, NE and cortisol, in their contribution to different processes related to decision making under risk and selective attention to threat. To this end, combined precise pharmacological stimulation, behavioral modeling, and fMRI methods will be applied to systematically disentangle the effects of stress hormones on risk attitudes and loss aversion as well as their relation to neural correlates of processing subjective value and risk. Using pharmacological manipulation, the influence of noradrenergic and glucocorticoid activity on decision making under risk at the behavioral, computational, and neural level will be investigated. In addition, the influence of noradrenergic and glucocorticoid activity on selective attention to threat at the behavioural and neural level using a dot-probe paradigm with fearful and neutral faces will be examined. Participants are randomly assigned to one of four groups: (A) yohimbine, (B) hydrocortisone, (C) yohimbine and hydrocortisone, or (D) placebo.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
167

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Nov 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2019

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

April 20, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 24, 2020

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 22, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 22, 2021

Completed
Last Updated

March 15, 2022

Status Verified

March 1, 2022

Enrollment Period

2.1 years

First QC Date

April 20, 2020

Last Update Submit

March 14, 2022

Conditions

Outcome Measures

Primary Outcomes (4)

  • Risk and loss-aversion, choice consistency

    Behavioural outcome of the decision-making under risk task modeled using prospect theory (PT)

    45 minutes

  • Patch-leaving times

    Behavioural outcome of the decision-making under risk task including a foraging task part using marginal value theory

    45 minutes

  • Attentional bias to fearful faces

    Behavioural outcome of the dot-probe task

    12 minutes

  • Blood-oxygen-level-dependent (BOLD) response

    In both tasks

    45 + 12 minutes

Secondary Outcomes (4)

  • Salivary cortisol

    3 hours

  • Salivary alpha amylase

    3 hours

  • Systolic and diastolic blood pressure

    3 hours

  • Heart rate

    3 hours

Study Arms (4)

Yohimbine

ACTIVE COMPARATOR

10 mg

Drug: "Yohimbine"

Hydrocortisone

ACTIVE COMPARATOR

10 mg

Drug: "Hydrocortisone"

Yohimbine + Hydrocortisone

ACTIVE COMPARATOR

10 mg each

Drug: "Yohimbine + Hydrocortisone"

Placebo

PLACEBO COMPARATOR
Drug: "Placebo"

Interventions

Effects on neural correlates of decision-making under risk and selective attention to threat

Also known as: Pill (oral administration)
Yohimbine

Effects on neural correlates of decision-making under risk and selective attention to threat

Also known as: Pill (oral administration)
Hydrocortisone

Effects on neural correlates of decision-making under risk and selective attention to threat

Also known as: Pill (oral administration)
Yohimbine + Hydrocortisone

Effects on neural correlates of decision-making under risk and selective attention to threat

Also known as: Pill (oral administration)
Placebo

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Right-handed
  • High-school diploma

You may not qualify if:

  • Former and present DSM-5 axis I disorders according to the Structured Clinical Interview for DSM (SCID)
  • Permanent medication of any kind
  • Medical conditions associated with adrenal dysfunction or well-known impact on HPA activity or cognitive function
  • Steroid use

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Charite University

Berlin, Germany

Location

Related Publications (1)

  • Rosada C, Lipka R, Metz S, Otte C, Heekeren H, Wingenfeld K. Effects of stress-related neuromodulators on amygdala and hippocampus resting state functional connectivity. J Psychopharmacol. 2024 Jul;38(7):604-614. doi: 10.1177/02698811241260972. Epub 2024 Jun 20.

MeSH Terms

Interventions

YohimbineAdministration, OralHydrocortisone

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesDrug Administration RoutesDrug TherapyTherapeuticsPregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-Hydroxycorticosteroids

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 20, 2020

First Posted

April 24, 2020

Study Start

November 1, 2019

Primary Completion

December 22, 2021

Study Completion

December 22, 2021

Last Updated

March 15, 2022

Record last verified: 2022-03

Locations