Inflammatory Challenge and Fear

NCT ID: NCT06630884

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-28
• Study Completion Date: 2028-11-30

Brief 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.

Detailed Description

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. The 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. The 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. The central hypothesis is that acute inflammatory challenge will alter fear responding, with particularly strong effects in people with chronic PTSD and women. The 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 the proposed study, we will use polysaccharide typhoid vaccine, which 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, participants 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.

Conditions

Posttraumatic Stress Disorder (PTSD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Polysaccharide typhoid vaccine

Participants in this condition will receive an injection of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA), which contains 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection.

Group Type: EXPERIMENTAL

Typhoid VI Polysaccharide Vaccine Injectable Solution

Intervention Type: BIOLOGICAL

Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.

Saline Placebo Arm

Participants in this condition will receive and injection of 0.5ml of saline.

Group Type: PLACEBO_COMPARATOR

Saline Placebo (0.5mL injection)

Intervention Type: OTHER

The placebo injection will consist of 0.5mL of saline.

Interventions

Typhoid VI Polysaccharide Vaccine Injectable Solution

Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.

Intervention Type: BIOLOGICAL

Saline Placebo (0.5mL injection)

The placebo injection will consist of 0.5mL of saline.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

All Subjects:

1. Aged 18-60 years old

2. Trauma Exposed

3. Current PTSD/No history of PTSD

Exclusion Criteria

1. Contraindications to typhoid vaccine

2. Conditions associated with inflammation

3. Pregnancy or plans to become pregnant in next three months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Northern California Institute of Research and Education

OTHER

Sponsor Role: collaborator

San Francisco Veterans Affairs Medical Center

FED

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aoife O'Donovan, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

San Francisco VA Health Care System

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Aoife O'Donovan, PhD

Role: CONTACT

aoife.odonovan@ucsf.edu

415-221-4810

Michael Srouji, BA

Role: CONTACT

415-221-4810

Related Links

http://odonovanlab.ucsf.edu

Related Info

Other Identifiers

R01MH135076

Identifier Type: NIH

Identifier Source: secondary_id

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R01MH135076

Identifier Type: NIH

Identifier Source: org_study_id

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