Inflammatory Challenge and Fear
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Interventions
- Other: Saline Placebo (0.5mL injection)
- Registration Number
- NCT06630884
- Lead Sponsor
- University of California, San Francisco
- 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. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 288
All Subjects:
- Aged 25-45 years old
- Trauma Exposed
- Current PTSD/No history of PTSD
- Contraindications to typhoid vaccine
- Conditions associated with inflammation
- Pregnancy or plans to become pregnant in next three months
- Lack of skin conductance response to breathing and arithmetic tasks at screening visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Polysaccharide typhoid vaccine Typhoid VI Polysaccharide Vaccine Injectable Solution 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. Saline Placebo Arm Saline Placebo (0.5mL injection) Participants in this condition will receive and injection of 0.5ml of saline.
- Primary Outcome Measures
Name Time Method Skin conductance response (SCR) SCR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo. Skin conductance level (SCL)will be sampled at 1000 Hz beginning 2 s prior to the conditioned stimulus (CS) onset and continuing until 6 s following CS offset. The skin conductance response (SCR) score for each CS interval will be obtained by subtracting the mean SCL for the 2 s preceding CS onset from the peak during the 8 s CS interval.
- Secondary Outcome Measures
Name Time Method Heart rate HR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo. HR will be calculated by subtracting average HR of every 0.5 s interval during 6 s before CS (baseline) from peak HR during 0.5 s interval of 8 s after CS onset (response).
Eyeblink electromyography (EMG) Eyeblink EMG will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo. EMG will be calculated by subtracting the mean signal amplitude during 2 s preceding CS onset (baseline) from the peak during the 8 s CS interval (response).
Trial Locations
- Locations (1)
San Francisco VA Health Care System
🇺🇸San Francisco, California, United States