HealthyEarly Phase 1NCT03294564
Cognitive, Emotional, and Neural Responses to Acute Inflammation
A Early Phase 1 study testing Typhoid Vi Polysaccharide Vaccine in people with Healthy, run by University of California, San Francisco at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Typhoid Vi Polysaccharide Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2018to 30 Dec 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 30 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy individuals (free of chronic illness or lifetime history of psychiatric disorder)
- Non-smokers
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
San Francisco Veterans Affairs Medical Center
San Francisco, California, 94121
University of California, San Francisco
San Francisco, California, 94143
About this study
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Typhoid Vi Polysaccharide Vaccine, Placebo
- Keywords
- Inflammation, Threat sensitivity, Reward sensitivity
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Typhoid Vi Polysaccharide VaccineBiological
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.
PlaceboBiological
The placebo injection will consist of 0.5mL of saline.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Typhoid Vi Polysaccharide Vaccine |
| Placebo | Placebo comparator | Patients will receive one intramuscular 0.5 mL injection of saline placebo. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5-7 hours
Secondary outcomes (2)
Threat sensitivity between groups
Participants will complete questionnaires and perform computerized tasks designed to assess threat sensitivity
Measured: 1-3 hours
Reward sensitivity between groups
Participants will complete questionnaires and perform computerized tasks designed to assess reward sensitivity
Measured: 1-2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2017
- Study start1 Jan 2018
- Primary completion30 Dec 2018
- Study completion30 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Aoife S O'Donovan, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03294564
- Sponsor's protocol ID
- 14-13204
- Other IDs
- K01MH109871
- Status last verified
- Jun 2019
- First submitted
- 22 Sep 2017
- Last updated
- 25 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive, Emotional, and Neural Responses to Acute Inflammation
- ClinicalTrials.gov ID
- NCT03294564
- Acronym / sponsor ID
- 14-13204
- Conditions
- Healthy
- Keywords
- Inflammation, Threat sensitivity, Reward sensitivity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 27 Sep 2017 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Typhoid Vi Polysaccharide Vaccine | Active comparator | Biological: Typhoid Vi Polysaccharide VaccinePatients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide. |
| Placebo | Placebo comparator | Biological: PlaceboPatients will receive one intramuscular 0.5 mL injection of saline placebo. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy individuals (free of chronic illness or lifetime history of psychiatric disorder)
- Non-smokers
Key exclusion criteria (12 listed)
- 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.
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 VaccineSalmonella 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 | Typhoid Vi Polysaccharide Vaccine |
| PlaceboThe placebo injection will consist of 0.5mL of saline. | Biological | Placebo |
Primary outcome
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
2 secondary outcomes
Threat sensitivity between groups
Time frame: 1-3 hours
Reward sensitivity between groups
Time frame: 1-2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Aoife S O'Donovan, PhD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Typhoid Vi Polysaccharide Vaccine in people with Healthy, run by University of California, San Francisco at 2 sites 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 2 inclusion and 12 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: finished, as of the sponsor's last update on 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammatory markers elicited by the typhoid vaccine (time frame: 5-7 hours). 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 25 Jun 2019.