Summary

Eligibility
for people ages 25-45 (full criteria)
Healthy Volunteers
healthy people welcome
Location
at San Francisco, California
Dates
study started
completion around
Principal Investigator
by Aoife O'Donovan, PhD

Description

Summary

The goal of this study is to learn if short-term changes in the immune system alter how we process information and experience fear. The main questions it aims to answer are:

Do people who receive typhoid vaccine respond differently than those who receive a placebo saline vaccine? Do people who receive typhoid vaccine experience changes in how they think and feel?

Participants will:

Attend four appointments at the San Francisco VA Health Care System;

Receive typhoid vaccine or placebo at one of the visits;

Have their physiological responding measured while listening to sounds;

Complete questionnaires and psychological tests.

Official Title

Inflammatory Challenge and Fear Extinction: A Model to Enhance Understanding of Posttraumatic Stress Disorder

Details

Posttraumatic stress disorder (PTSD) is a chronic disorder affecting more than 8% of the general population and two-three times as many women as men. Deficits in fear responding play a critical role in PTSD. Interventions that target fear responding are first-line treatments for PTSD, but they are only partially effective. To develop new and enhanced interventions, we need a better understanding of the factors that influence fear responding in PTSD in both females and males. One such factor is inflammation, which is elevated in response to acute psychological stress and in PTSD. Preclinical models indicate that elevated inflammation in general, and elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in particular, can impair fear responses. People with PTSD and women may be more sensitive to the effects of inflammatory activity on fear responses. Our long-term goal is to uncover the mechanistic role that inflammation plays in PTSD in order to identify effective primary and adjunctive anti-inflammatory interventions. Our objective in this proposal is to determine the effects of acute inflammatory challenge on fear responding in trauma-exposed women and men with and without PTSD. Our central hypothesis is that acute inflammatory challenge will alter fear responding, with particularly strong effects in people with chronic PTSD and women. Our aims are to: 1) determine the effects of acute inflammatory challenge on fear responding in individuals with and without PTSD; 2) examine if increases in inflammatory activity mediate associations between acute inflammatory challenge and fear responses; and 3) elucidate sex differences in the effects of acute inflammatory challenge on fear responses. In our proposed study, we will use polysaccharide typhoid vaccine, which our preliminary data support as a robust acute inflammatory challenge, and a fear learning paradigm that we have used in >200 people with PTSD. Participants will first undergo physiological testing of fear responses. Then, three days later, they will receive either vaccine or placebo and undergo more tests, including physiological tests. One week later, we will test physiological responses again. Inflammatory markers will be measured at baseline, twice on the the vaccine/placebo day, and once at the one-week follow-up visit. This proposal is significant and innovative because it would be the first study to examine the effects of acute inflammatory activity on fear responses in trauma-exposed individuals with and without PTSD, and it has potential to elucidate biological mechanisms of impaired fear responses, uncover sex differences, and point us in the direction of novel interventions to treat PTSD.

Keywords

Posttraumatic Stress Disorder (PTSD), PTSD, posttraumatic stress, inflammation, fear, Traumatic Stress Disorders, Post-Traumatic Stress Disorders, Typhoid VI Polysaccharide Vaccine Injectable Solution, Polysaccharide typhoid vaccine

Eligibility

You can join if…

Open to people ages 25-45

All Subjects:

  1. Aged 25-45 years old
  2. Trauma Exposed
  3. Current PTSD/No history of PTSD

You CAN'T join if...

  1. Contraindications to typhoid vaccine
  2. Conditions associated with inflammation
  3. Pregnancy or plans to become pregnant in next three months
  4. Lack of skin conductance response to breathing and arithmetic tasks at screening visit

Location

  • San Francisco VA Health Care System
    San Francisco California 94121 United States

Lead Scientist at UCSF

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
Links
Related Info
ID
NCT06630884
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 288 study participants
Last Updated