Inflammatory Challenge and Fear (LIFE)

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 1

Conditions: Posttraumatic Stress Disorder (PTSD)

Treatments: Other: Saline Placebo (0.5mL injection); Biological: Typhoid VI Polysaccharide Vaccine Injectable Solution

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT06630884

R01MH135076 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 288 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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288 participants in 2 patient groups, including a placebo group

Polysaccharide typhoid vaccine

Experimental group

Description:

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.

Treatment:

Biological: Typhoid VI Polysaccharide Vaccine Injectable Solution

Saline Placebo Arm

Placebo Comparator group

Description:

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

Treatment:

Other: Saline Placebo (0.5mL injection)