NCT03048929

Inflammation and Threat Sensitivity in PTSD

Effects of Inflammation on Neural Mechanisms of Threat Sensitivity in Posttraumatic Stress Disorder

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 30 Years – 60 Years
• Healthy volunteers: Accepted

Summary

The overall goals of this study are to examine the relationship between chronic inflammation and threat and reward sensitivity, and to determine the effects of acute inflammation on threat sensitivity, in individuals with and without moderate to severe PTSD symptoms. The investigators will first conduct an observational study to examine the relationship between chronic inflammation and neural and behavioral measures of threat sensitivity. Then, the investigators will conduct a randomized, double-blind, placebo-controlled, between-subjects study to examine the effects of acute inflammation on neural and behavioral measures of threat sensitivity.

Detailed description

Posttraumatic stress disorder (PTSD) is a disabling chronic psychiatric disorder that affects more than 8% of the population. New treatments for PTSD symptoms are desperately needed because current pharmacologic and behavioral treatments for PTSD are inadequate or they have low uptake. Accumulating evidence supports elevated inflammation as a new potential treatment target for PTSD. Inflammation is increased in PTSD, and can promote threat sensitivity, a core mechanism underlying several PTSD symptoms. Two major gaps in knowledge prevent progress towards effective anti- inflammatory treatments for PTSD symptoms. First, researchers know little about the relationship between chronic inflammation and exaggerated threat sensitivity. Second, no studies have directly examined the effects of acute inflammation on neural and behavioral measures of threat sensitivity in PTSD. The objective of this study is to uncover the effects of chronic and acute inflammation on neural mechanisms and behavioral measures of threat sensitivity in individuals with and without PTSD symptoms. The central hypothesis is that both chronic and acute inflammation will be associated with exaggerated threat sensitivity overall, with particularly strong relationships in PTSD. The scientific rationale is that establishing a link between elevated inflammation and threat sensitivity in both observational and experimental studies in individuals with and without PTSD symptoms will drive progress towards a targeted approach to identifying effective anti- inflammatory treatments for PTSD symptoms. In particular, this work has the potential to identify a target for clinical trials of anti-inflammatory interventions in PTSD. Guided by preliminary data, hypotheses will be tested by pursuing two specific aims: 1) Examine the association of chronic inflammation with threat sensitivity; and 2) Determine the effects of an acute inflammatory challenge on threat sensitivity. To achieve these aims, 40 participants with moderate to severe PTSD symptoms and 40 age- and body mass index-matched trauma-exposed participants with no history of PTSD will be recruited. The investigators will assess chronic resting levels of inflammation (Aim 1) and will randomize participants to placebo or inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) (Aim 2) and will use validated functional MRI paradigms and behavioral tasks to assess threat sensitivity.

Conditions

• Posttraumatic Stress Disorder

Interventions

Type	Name	Description
BIOLOGICAL	Typhoid Vi Polysaccharide Vaccine	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.
BIOLOGICAL	Placebo	The placebo injection will consist of 0.5mL of saline.

Timeline

• Start date: 2019-04-01
• Primary completion: 2020-03-30
• Completion: 2021-03-31
• First posted: 2017-02-09
• Last updated: 2021-05-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study