Acute Plasma Abeta Responses to Stress

Effects of Acute Stress Exposure on Plasma Beta-amyloid Levels

Research has shown that activation of the sympathetic nervous system for extended periods or during certain times in life can increase the risk for Alzheimer's disease. Some research in animal models show that acute activation of the sympathetic nervous system through stress exposure can increase certain Alzheimer's disease-related biomarkers, such as amyloid-beta, within hours of exposure. However, how acute sympathetic nervous system activation via stress exposure affects amyloid-beta levels in humans has yet to be examined.

In this study, the investigators will examine whether brief increases in sympathetic activation result in immediate changes in plasma amyloid-beta levels in the five hours after exposure.

Study Overview

• Status: Recruiting
• Conditions: Stress Physiology; Stress Reaction
• Intervention / Treatment: Behavioral: Sympathetic Nervous System Activation; Behavioral: No-stress

Detailed Description

Aim 1: determine whether acute exposure to stress (increasing sympathetic nervous system activation) increases plasma amyloid-beta-40 and amyloid-beta-42 in the five hours following exposure.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lab Manager; Phone Number: 213-740-9543; Email: matherlab@usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • Recruiting
      • University of Southern California
      • Contact: Mara Mather, Ph.D.; Phone Number: 213-740-9543; Email: matherlab@usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adult weighing at least 110 pounds
• No chronic conditions or illness
• Taking no medications or drugs that might alter the stress response (e.g., corticosteroids, beta-blockers, and others)
• Not using any hormone-containing medication (e.g., hormonal contraceptives, hormone replacement, etc.)
• No contraindications for cold pressor test exposure (high blood pressure, heart disease, dysrhythmia, peripheral vascular disease, any other cardiovascular disorder, diabetes, vasculitis, lupus, tingling or numbness in the hands and/or feet, cryoglobulinemia, and Reynaud's phenomenon)
• No history of fainting during blood draws
• No phobia of having their blood drawn
• No general history of fainting or seizures
• Not currently diagnosed with a mood disorder (e.g., major depressive disorder)
• Not pregnant in the past 12 months
• Not lactating in the past 12 months
• Not trying to become pregnant if premenopausal
• Experienced natural menopause if postmenopausal
• Be non-smokers
• Be fluent in English

Exclusion Criteria:

- Unwilling to be filmed during the stress task OR unwilling to sign the waiver allowing their filmed responses to be used in scientific presentations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: No-stress; Participants will hold a hand in room temperature water for 3 minutes.	Behavioral: No-stress; Participants will complete a task that will not affect their sympathetic nervous system activity.
Experimental: Stress (sympathetic nervous system activation); Stress will be induced using the socially evaluated cold pressor test. Participants will complete three rounds of the socially evaluated cold pressor test. The socially evaluated cold pressor test involves submerging one hand in ice-cold water for 3 minutes while participants' reactions are filmed on camera.	Behavioral: Sympathetic Nervous System Activation; Participants will complete a task that increases sympathetic nervous system activation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma amyloid-beta-40	Changes in levels of amyloid-beta-40 in blood from before to after acute intervention (stress/no-stress).	9.5 hours
Plasma amyloid-beta-42	Changes in levels of amyloid-beta-42 in blood from before to after acute intervention (stress/no-stress).	9.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary amyloid-beta-42	Change in urine levels of amyloid-beta-42 from before to after acute intervention (stress/no-stress).	9.5 hours

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Washington University School of Medicine; Keck School of Medicine of USC

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Stress; Stress Reaction; Amyloid-Beta
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Fractures, Stress
• Other Study ID Numbers: UP-22-00404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data (values of outcome measures and associated experimental conditions) will be shared publicly on Open Science Framework.
• IPD Sharing Time Frame: Data will be made available by publication of the paper reporting on the results.
• IPD Sharing Access Criteria: Publicly available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No