Cognitive, Emotional, and Neural Responses to Acute Inflammation
|ClinicalTrials.gov Identifier: NCT03294564|
Recruitment Status : Completed
First Posted : September 27, 2017
Last Update Posted : June 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Biological: Typhoid Vi Polysaccharide Vaccine Biological: Placebo||Early Phase 1|
The inflammatory response of the immune system is responsive to stress and it impacts brain function. Animal studies have shown that inflammation appears to alter threat- and reward-related brain activity. Accumulating evidence points to inflammatory proteins, specifically cytokines, as key players in this relationship. Although cytokines are typically too large to pass through the blood brain barrier (BBB), they can influence brain function and structure by transmitting signals from peripheral systems to the brain.
The administration of endotoxin within the polysaccharide form of Salmonella typhi vaccination provides an ideal model for studying the causal effects of short-term inflammation on thinking patterns (i.e., cognition) and emotions in the brain. Endotoxin is a component of the cell walls of Gram-negative bacteria, which promotes the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) via toll-like receptor-4 (TLR-4) activation and nuclear factor- κB (NF-κB) signaling.
To examine the effects of acute inflammation on brain functioning, 24 healthy participants will be recruited. The investigators will will randomize participants to placebo or inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) and will use validated behavioral tasks and questionnaires to assess threat and reward sensitivity. They will assess chronic resting levels of inflammation as well as the inflammatory response to Salmonella typhi vaccination.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Cognitive, Emotional, and Neural Responses to Acute Inflammation|
|Actual Study Start Date :||January 1, 2018|
|Actual Primary Completion Date :||December 30, 2018|
|Actual Study Completion Date :||December 30, 2018|
Active Comparator: Typhoid Vi Polysaccharide Vaccine
Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide.
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.
Placebo Comparator: Placebo
Patients will receive one intramuscular 0.5 mL injection of saline placebo.
The placebo injection will consist of 0.5mL of saline.
- Inflammatory markers elicited by the typhoid vaccine [ Time Frame: 5-7 hours ]Participants will receive a vaccine or placebo and investigators will examine inflammation levels during three different time points via blood draws
- Threat sensitivity between groups [ Time Frame: 1-3 hours ]Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity
- Reward sensitivity between groups [ Time Frame: 1-2 hours ]Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03294564
|United States, California|
|San Francisco Veterans Affairs Medical Center|
|San Francisco, California, United States, 94121|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|Principal Investigator:||Aoife S O'Donovan, PhD||University of California, San Francisco|