Cognitive, Emotional, and Neural Responses to Acute Inflammation

June 21, 2019 updated by: University of California, San Francisco
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
      • San Francisco, California, United States, 94121
        • San Francisco Veterans Affairs Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
5-7 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Threat sensitivity between groups
Time Frame: 1-3 hours
Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity
1-3 hours
Reward sensitivity between groups
Time Frame: 1-2 hours
Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity
1-2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Francisco

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 25, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14-13204
  • K01MH109871 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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