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Cognitive, Emotional, and Neural Responses to Acute Inflammation

Primary Purpose

Healthy

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Typhoid Vi Polysaccharide Vaccine

Placebo

About this trial

This is an interventional basic science trial for Healthy focused on measuring Inflammation, Threat sensitivity, Reward sensitivity

Eligibility Criteria

30 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

San Francisco Veterans Affairs Medical Center
University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Typhoid Vi Polysaccharide Vaccine

Placebo

Arm Description

Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide.

Patients will receive one intramuscular 0.5 mL injection of saline placebo.

Outcomes

Primary Outcome Measures

Inflammatory markers elicited by the typhoid vaccine

Participants will receive a vaccine or placebo and investigators will examine inflammation levels during three different time points via blood draws

Secondary Outcome Measures

Threat sensitivity between groups

Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity

Reward sensitivity between groups

Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity

Full Information

NCT ID

NCT03294564

First Posted

September 22, 2017

Last Updated

June 21, 2019

Sponsor

University of California, San Francisco

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT03294564

Brief Title

Cognitive, Emotional, and Neural Responses to Acute Inflammation

Official Title

Cognitive, Emotional, and Neural Responses to Acute Inflammation

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

January 1, 2018 (Actual)

Primary Completion Date

December 30, 2018 (Actual)

Study Completion Date

December 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy

Keywords

Inflammation, Threat sensitivity, Reward sensitivity

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Typhoid Vi Polysaccharide Vaccine

Arm Type

Active Comparator

Arm Description

Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients will receive one intramuscular 0.5 mL injection of saline placebo.

Intervention Type

Biological

Intervention Name(s)

Typhoid Vi Polysaccharide Vaccine

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

The placebo injection will consist of 0.5mL of saline.

Primary Outcome Measure Information:

Title

Inflammatory markers elicited by the typhoid vaccine

Description

Participants will receive a vaccine or placebo and investigators will examine inflammation levels during three different time points via blood draws

Time Frame

5-7 hours

Secondary Outcome Measure Information:

Title

Threat sensitivity between groups

Description

Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity

Time Frame

1-3 hours

Title

Reward sensitivity between groups

Description

Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity

Time Frame

1-2 hours

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aoife S O'Donovan, PhD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

San Francisco Veterans Affairs Medical Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94121

Country

United States

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Cognitive, Emotional, and Neural Responses to Acute Inflammation

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