Inflammation and Threat Sensitivity in PTSD

NCT03048929 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 15-18367K01MH109871
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Neural activity to threat as assessed with functional magnetic resonance imaging

  On visits 1 (baseline) and 2 (post-vaccine or post-placebo administration), participants will perform computerized threat and reward tasks and investigators will measure and compare neural activity between groups (PTSD vs. control) and condition (endotoxin vs. placebo).

  Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)

Secondary Outcomes (1)

• Threat sensitivity

  Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)

Study Arms (2)

Typhoid Vi Polysaccharide Vaccine

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

Typhoid Vi Polysaccharide Vaccine BIOLOGICAL

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.

Typhoid Vi Polysaccharide Vaccine

Placebo BIOLOGICAL

The placebo injection will consist of 0.5mL of saline.

Placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All Subjects:
• Veterans aged 30-60.
• PTSD Subjects:
• Positive for current chronic moderate to severe PTSD symptoms of at least three months duration as indexed by the Clinically Administered PTSD Scale for DSM 5 (CAPS-5).
• Control Subjects:
• Negative for lifetime PTSD.
• Negative for lifetime diagnosis of Mood Disorders, Generalized Anxiety Disorder, Obsessive-Compulsive Disorder and Panic Disorder.

You may not qualify if:

• All Subjects:
• Lifetime history of any psychiatric disorder with psychotic features, bipolar disorder, panic 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.
• Diagnosis of neurologic disorder, systemic illness affecting central nervous system function, and/or anemia.
• Prominent suicidal or homicidal ideation.
• Current and planned ongoing use of medications that impact inflammation or immune function, or use of such medications in the past 6 months.
• Subjects currently receiving serotonin reuptake inhibitors (SSRIs), benzodiazepine or benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, any antidepressant medication including trazodone.
• 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 Magnetic Resonance Imaging (MRI), which include claustrophobia severe enough to prevent MRI examination and presence of ferrometallic objects in the body that would interfere with MR examination and/or cause a safety risk (e.g., pace makers, implanted stimulators, pumps).
• Contraindications to typhoid vaccine, which include acute febrile illness within the past two weeks, disorders characterized by a deficiency in ability to mount a humoral or cell-mediated immune response, use of anti-malarial medications in past six months, antibiotics in past three months, a history of hypersensitivity to typhoid vaccine or any other vaccine, previous immunization with whole-cell typhoid or live, oral typhoid vaccine, vaccination with the polysaccharide version of the typhoid vaccine within the past 3 year, coagulation disorders and thrombocytopenia.
• Conditions or use of substances that may be associated with inflammation independent of trauma and PTSD, including chronic physical disease.
• History of neurologic disorders, traumatic brain injury (TBI), brain tumor, brain hemorrhage, or head injury with loss of consciousness.
• Women who are currently, or are planning to become, pregnant during the study.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

San Francisco Veterans Affairs Medical Center

San Francisco, California, 94121, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Vi polysaccharide vaccine, typhoid

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Aoife S O'Donovan, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 9, 2017
• Study Start: April 1, 2019
• Primary Completion: March 30, 2020
• Study Completion: March 31, 2021
• Last Updated: May 13, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)