Posttraumatic Stress Disorder (PTSD)Phase 1LIFENCT06630884
Inflammatory Challenge and Fear
A Phase 1 study testing Typhoid VI Polysaccharide Vaccine Injectable Solution in people with Posttraumatic Stress Disorder (PTSD), run by University of California, San Francisco at 1 site in United States.
Trial summary
The goal of this study is to learn if short-term changes in the immune system alter how we process information and experience fear. The main questions it aims to answer are: Do people who receive typhoid vaccine respond differently than those who receive a placebo saline vaccine? Do people who receive typhoid vaccine… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Posttraumatic Stress Disorder (PTSD)
- What is being tested?
- Typhoid VI Polysaccharide Vaccine Injectable Solution
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2025to Nov 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All Subjects:
- Aged 18-65 years old
- Trauma Exposed
- Current PTSD/No history of PTSD
Who cannot join
- Contraindications to typhoid vaccine
- Conditions associated with inflammation
- Pregnancy or plans to become pregnant in next three months
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Michael Srouji, BA contact
United States1 site, 1 recruiting
- Recruiting
San Francisco VA Health Care System
San Francisco, California, 94121
About this study
Official title: Inflammatory Challenge and Fear Extinction: A Model to Enhance Understanding of Posttraumatic Stress Disorder
The goal of this study is to learn if short-term changes in the immune system alter how we process information and experience fear. The main questions it aims to answer are:
Do people who receive typhoid vaccine respond differently than those who receive a placebo saline vaccine? Do people who receive typhoid vaccine experience changes in how they think and feel?
Participants will:
Attend four appointments at the San Francisco VA Health Care System;
Receive typhoid vaccine or placebo at one of the visits;
Have their physiological responding measured while listening to sounds;
Complete questionnaires and psychological tests.
Read the detailed description
Posttraumatic stress disorder (PTSD) is a chronic disorder affecting more than 8% of the general population and two-three times as many women as men. Deficits in fear responding play a critical role in PTSD. Interventions that target fear responding are first-line treatments for PTSD, but they are only partially effective. To develop new and enhanced interventions, we need a better understanding of the factors that influence fear responding in PTSD in both females and males. One such factor is inflammation, which is elevated in response to acute psychological stress and in PTSD. Preclinical models indicate that elevated inflammation in general, and elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in particular, can impair fear responses. People with PTSD and women may be more sensitive to the effects of inflammatory activity on fear responses. The long-term goal is to uncover the mechanistic role that inflammation plays in PTSD in order to identify effective primary and adjunctive anti-inflammatory interventions. The objective in this proposal is to determine the effects of acute inflammatory challenge on fear responding in trauma-exposed women and men with and without PTSD. The central hypothesis is that acute inflammatory challenge will alter fear responding, with particularly strong effects in people with chronic PTSD and women. The aims are to: 1) determine the effects of acute inflammatory challenge on fear responding in individuals with and without PTSD; 2) examine if increases in inflammatory activity mediate associations between acute inflammatory challenge and fear responses; and 3) elucidate sex differences in the effects of acute inflammatory challenge on fear responses. In the proposed study, we will use polysaccharide typhoid vaccine, which preliminary data support as a robust acute inflammatory challenge, and a fear learning paradigm that we have used in >200 people with PTSD. Participants will first undergo physiological testing of fear responses. Then, three days later, participants will receive either vaccine or placebo and undergo more tests, including physiological tests. One week later, we will test physiological responses again. Inflammatory markers will be measured at baseline, twice on the the vaccine/placebo day, and once at the one-week follow-up visit. This proposal is significant and innovative because it would be the first study to examine the effects of acute inflammatory activity on fear responses in trauma-exposed individuals with and without PTSD, and it has potential to elucidate biological mechanisms of impaired fear responses, uncover sex differences, and point us in the direction of novel interventions to treat PTSD.
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Being tested
- Typhoid VI Polysaccharide Vaccine Injectable Solution, Saline Placebo (0.5mL injection)
- Keywords
- PTSD, posttraumatic stress, inflammation, fear
- Medical subject headings
- Stress Disorders, Post-Traumatic, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Typhoid VI Polysaccharide Vaccine Injectable SolutionBiological
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.
Saline Placebo (0.5mL injection)Other
The placebo injection will consist of 0.5mL of saline.
| Study group | Role | What they receive |
|---|---|---|
| Polysaccharide typhoid vaccine | Experimental | Participants in this condition will receive an injection of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA), which contains 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. Receives: Biological: Typhoid VI Polysaccharide Vaccine Injectable Solution |
| Saline Placebo Arm | Placebo comparator | Participants in this condition will receive and injection of 0.5ml of saline. Receives: Other: Saline Placebo (0.5mL injection) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin conductance response (SCR)
Skin conductance level (SCL)will be sampled at 1000 Hz beginning 2 s prior to the conditioned stimulus (CS) onset and continuing until 6 s following CS offset. The skin conductance response (SCR) score for each CS interval will be obtained by subtracting the mean SCL for the 2 s preceding CS onset from the peak during the 8 s CS interval.
Measured: SCR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Secondary outcomes (2)
Heart rate
HR will be calculated by subtracting average HR of every 0.5 s interval during 6 s before CS (baseline) from peak HR during 0.5 s interval of 8 s after CS onset (response).
Measured: HR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Eyeblink electromyography (EMG)
EMG will be calculated by subtracting the mean signal amplitude during 2 s preceding CS onset (baseline) from the peak during the 8 s CS interval (response).
Measured: Eyeblink EMG will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2024
- Study start28 Mar 2025
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress Disorder (PTSD)Studies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Northern California Institute of Research and Education, San Francisco Veterans Affairs Medical Center
- Responsible party
- Sponsor
- Investigators
- Aoife O'Donovan, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06630884
- Sponsor's protocol ID
- R01MH135076
- Other IDs
- R01MH135076
- Acronym
- LIFE
- Status last verified
- Sep 2026
- First submitted
- 4 Oct 2024
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Demographic, clinical, biological, and psychophysiological data will be acquired from 120 individuals with PTSD and 120 individuals without PTSD. Demographic data will be self-reported. Clinical data will include information from validated semi-structured clinical interviews and validated self-report measures assessing symptoms of PTSD and other psychiatric disorders. Biological data will include levels of eleven inflammatory markers derived from five blood draws for each participant. Psychophysiological data will include skin conductance level, heart rate (HR), and HR variability (HRV) assessed 34 times for each participant.
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory Challenge and Fear Extinction: A Model to Enhance Understanding of Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT06630884
- Acronym / sponsor ID
- LIFE / R01MH135076
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Keywords
- PTSD, posttraumatic stress, inflammation, fear
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Northern California Institute of Research and Education, San Francisco Veterans Affairs Medical Center
- Study start
- 28 Mar 2025 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 8 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to learn if short-term changes in the immune system alter how we process information and experience fear. The main questions it aims to answer are:
Do people who receive typhoid vaccine respond differently than those who receive a placebo saline vaccine? Do people who receive typhoid vaccine experience changes in how they think and feel?
Participants will:
Attend four appointments at the San Francisco VA Health Care System;
Receive typhoid vaccine or placebo at one of the visits;
Have their physiological responding measured while listening to sounds;
Complete questionnaires and psychological tests.
Detailed description
Posttraumatic stress disorder (PTSD) is a chronic disorder affecting more than 8% of the general population and two-three times as many women as men. Deficits in fear responding play a critical role in PTSD. Interventions that target fear responding are first-line treatments for PTSD, but they are only partially effective. To develop new and enhanced interventions, we need a better understanding of the factors that influence fear responding in PTSD in both females and males. One such factor is inflammation, which is elevated in response to acute psychological stress and in PTSD. Preclinical models indicate that elevated inflammation in general, and elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in particular, can impair fear responses. People with PTSD and women may be more sensitive to the effects of inflammatory activity on fear responses. The long-term goal is to uncover the mechanistic role that inflammation plays in PTSD in order to identify effective primary and adjunctive anti-inflammatory interventions. The objective in this proposal is to determine the effects of acute inflammatory challenge on fear responding in trauma-exposed women and men with and without PTSD. The central hypothesis is that acute inflammatory challenge will alter fear responding, with particularly strong effects in people with chronic PTSD and women. The aims are to: 1) determine the effects of acute inflammatory challenge on fear responding in individuals with and without PTSD; 2) examine if increases in inflammatory activity mediate associations between acute inflammatory challenge and fear responses; and 3) elucidate sex differences in the effects of acute inflammatory challenge on fear responses. In the proposed study, we will use polysaccharide typhoid vaccine, which preliminary data support as a robust acute inflammatory challenge, and a fear learning paradigm that we have used in >200 people with PTSD. Participants will first undergo physiological testing of fear responses. Then, three days later, participants will receive either vaccine or placebo and undergo more tests, including physiological tests. One week later, we will test physiological responses again. Inflammatory markers will be measured at baseline, twice on the the vaccine/placebo day, and once at the one-week follow-up visit. This proposal is significant and innovative because it would be the first study to examine the effects of acute inflammatory activity on fear responses in trauma-exposed individuals with and without PTSD, and it has potential to elucidate biological mechanisms of impaired fear responses, uncover sex differences, and point us in the direction of novel interventions to treat PTSD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Polysaccharide typhoid vaccine | Experimental | Biological: Typhoid VI Polysaccharide Vaccine Injectable SolutionParticipants in this condition will receive an injection of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA), which contains 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. |
| Saline Placebo Arm | Placebo comparator | Other: Saline Placebo (0.5mL injection)Participants in this condition will receive and injection of 0.5ml of saline. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged 18-65 years old
- Trauma Exposed
- Current PTSD/No history of PTSD
Key exclusion criteria (3 listed)
- Contraindications to typhoid vaccine
- Conditions associated with inflammation
- Pregnancy or plans to become pregnant in next three months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Typhoid VI Polysaccharide Vaccine Injectable SolutionSalmonella 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. | Biological | Polysaccharide typhoid vaccine |
| Saline Placebo (0.5mL injection)The placebo injection will consist of 0.5mL of saline. | Other | Saline Placebo Arm |
Primary outcome
Skin conductance response (SCR)
Time frame: SCR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Skin conductance level (SCL)will be sampled at 1000 Hz beginning 2 s prior to the conditioned stimulus (CS) onset and continuing until 6 s following CS offset. The skin conductance response (SCR) score for each CS interval will be obtained by subtracting the mean SCL for the 2 s preceding CS onset from the peak during the 8 s CS interval.
2 secondary outcomes
Heart rate
Time frame: HR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Eyeblink electromyography (EMG)
Time frame: Eyeblink EMG will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Demographic, clinical, biological, and psychophysiological data will be acquired from 120 individuals with PTSD and 120 individuals without PTSD. Demographic data will be self-reported. Clinical data will include information from validated semi-structured clinical interviews and validated self-report measures assessing symptoms of PTSD and other psychiatric disorders. Biological data will include levels of eleven inflammatory markers derived from five blood draws for each participant. Psychophysiological data will include skin conductance level, heart rate (HR), and HR variability (HRV) assessed 34 times for each participant.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Srouji, BA contact
Aoife O'Donovan, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Typhoid VI Polysaccharide Vaccine Injectable Solution in people with Posttraumatic Stress Disorder (PTSD), run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aoife O'Donovan, PhD (415-221-4810, aoife.odonovan@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skin conductance response (SCR) (time frame: SCR will be assessed at baseline, 4.5 hours, and one week after vaccine/placebo.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.