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Cognitive, Emotional, and Neural Responses to Acute Inflammation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03294564
Recruitment Status : Completed
First Posted : September 27, 2017
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This study is a pilot study to examine the effects of acute inflammation on cognition and emotion in healthy participants using a between-subjects, randomized, double-blind design.

Condition or disease Intervention/treatment Phase
Healthy Biological: Typhoid Vi Polysaccharide Vaccine Biological: Placebo Early Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Biological: Placebo
The placebo injection will consist of 0.5mL of saline.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Threat sensitivity between groups [ Time Frame: 1-3 hours ]
    Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity

  2. Reward sensitivity between groups [ Time Frame: 1-2 hours ]
    Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy individuals (free of chronic illness or lifetime history of psychiatric disorder)
  • Non-smokers

Exclusion Criteria:

  • Lifetime history of an psychiatric disorder with psychotic features, bipolar disorder, obsessive-compulsive disorder, alcohol or substance dependence, or a history of alcohol or substance abuse within the past 2 years.
  • Currently exposed to recurrent trauma or have been exposed to a traumatic event within the past 3 months, or has current diagnosis of PTSD.
  • Diagnosis of sleep apnea, neurological disorder, systemic illness affective central nervous system function, and/or anemia.
  • Any suicidal or homicidal ideation within the past year.
  • Subjects currently receiving selective serotonin reuptake inhibitors (SSRIs), benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, any antidepressant medication including trazodone, or any psychotropic medication.
  • Termination of SSRIs, benzodiazepine or benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, any antidepressant medication including trazodone in the last month, or plans to start these medications during the course of the study.
  • Contraindications to fMRI, including severe claustrophobia and presence of ferromagnetic objects in the body that would interfere with magnetic resonance examination and/or cause a safety risk (e.g., pace makers, implanted stimulators, pumps, extensive dental work, upper body tattoos).
  • Contraindications to typhoid vaccine, which include acute febrile illness within the past two weeks, disorders characterized by a deficiency to ability to mount a humoral or cell-mediated immune response, use of anti-malarial medications in the past six months, antibiotics in past three months, a history of hypersensitivity to typhoid vaccine or any other vaccine, pervious immunization with whole-cell typhoid or live, oral typhoid vaccines, vaccination with the polysaccharide version of the typhoid vaccine within the past 3 years.
  • Conditions or use of substances that may be associated with inflammation, including drugs that affect the immune system.
  • Any chronic medical illness.
  • Having a body mass index (BMI) over 30.
  • Individuals who work the night shift

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03294564


Locations
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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
Sponsors and Collaborators
University of California, San Francisco
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Aoife S O'Donovan, PhD University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03294564    
Other Study ID Numbers: 14-13204
K01MH109871 ( U.S. NIH Grant/Contract )
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of California, San Francisco:
Inflammation
Threat sensitivity
Reward sensitivity
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes