HealthyPhase 1EndoscreenNCT02847247
Systemic Inflammatory Response to CCRE
A Phase 1 study testing CCRE in people with Healthy, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Purpose: The purpose of this study is to classify volunteers as endotoxin-responders or non-responders following inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE). Endotoxin is a commonly encountered bioaerosol and component of indoor and outdoor air pollution. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- CCRE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2017to 6 Aug 2019
- Phase
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be 18-50 years of age to be eligible for study participation
- Subjects must be willing to and able to provide informed consent and participate in all study procedures
- Normal lung function, defined as (Knudson 1976/1984 predicted set):
- 1. Forced Vital Capacity (FVC) of > 80% of that predicted for gender, ethnicity, age and height
- 2. Forced Expiratory Volume in the first second (FEV1) of > 80% of that predicted for gender, ethnicity, age and height
- 3. FEV1/FVC ratio of > 0.75 of that predicted for gender, ethnicity, age and height
- Oxygen saturation of > 94% Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
- Symptom Score (defined in section "f") no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.
Who cannot join
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
- Physician directed emergency treatment for asthma exacerbation within the preceding 3 months.
- Moderate or Severe asthma
- Exacerbation of asthma more than 2x/week that would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
- Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
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- History of intubation for asthma
- Daily use of NSAIDs, or inability to withhold NSAIDs for 4 days prior to dosing.
- Use of medications that may impact the results of the study to include, but not limited to, systemic corticosteroids, beta blockers.
- Cigarette smoking > 1 pack per month.
- BMI>35.
- Pregnant or breast feeding women will not be included.
- Subjects who are employed within the past 6 months in an occupation with high risk for endotoxin exposure, such as grain storage sites or swine containment.
- Subjects will be deferred after any acute, non-chronic medical condition requiring treatment, such as bronchitis, pneumonia or febrile illness for a minimum of 4 weeks after complete resolution of symptoms.
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Trial locations and contacts
1 site in 1 country.
United States1 site
Environmental Protection Agency Human Studies facility
Chapel Hill, North Carolina, 27599
About this study
Official title: Systemic Inflammatory Response to 20,000 EU Clinical Center Reference Endotoxin in Normal Adults
Purpose: The purpose of this study is to classify volunteers as endotoxin-responders or non-responders following inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE). Endotoxin is a commonly encountered bioaerosol and component of indoor and outdoor air pollution. For reasons that remain unclear, some individuals appear to be more susceptible to the inflammatory effects of inhaled endotoxin than are others, possibly owing to single nucleotide polymorphisms in the Toll-like receptor 4 (TLR4) gene that influence TLR4 signaling and function. These susceptible individuals represent a population of particular interest for further mechanistic studies of the effects of endotoxin and for therapeutic trials. Susceptibility to inhaled endotoxin will be determined by measuring change in peripheral blood neutrophil counts, a biomarker of systemic inflammation, following inhaled CCRE. In our previous work, the investigators have found that inhalation of 20,000 EU CCRE is well tolerated and induces measurable increase in neutrophil content of peripheral blood in susceptible individuals. Our hope is that this CCRE inhalation protocol can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin.
Read the detailed description
This is a single center, screening study involving recruitment of 18 normal volunteers (NV). The protocol is powered to compare absolute neutrophil count (ANC) in the blood 6 hours after inhalational challenge with CCRE compared baseline. In addition, as secondary endpoints, the investigators will evaluate inflammatory cytokine levels in systemic circulation and access for the presence of genes thought to be related to endotoxin response. Visits will be conducted by a study coordinator or other study staff, physical exams will be performed by the PI or other study physician.
Eighteen subjects will be recruited. There will be no gender or ethnic restrictions, and subjects will be healthy volunteers. Prior to enrollment in this study, subjects will have participated in our protocol 98-0799 (screening and database study for the CEMALB). Data such as medical history and allergy skin testing collected during the screening protocol will be included with data in this study. Subjects with positive allergy skin testing will not be excluded. Spirometry will be performed to determine the current level of lung function.
In order to identify those individuals who appear more susceptible to the systemic inflammatory effects of endotoxin exposure, subjects will undergo inhaled endotoxin challenge at the baseline visit followed 6 hours later by blood draw for complete blood count with differential to allow for calculation of absolute neutrophil count (ANC). Subjects will be considered "responders" if their peripheral ANC increases by at least 20% following inhaled endotoxin challenge.
- Conditions
- Healthy
- Being tested
- CCRE
- Keywords
- healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CCREDrug
Also called endotoxin, lipopolysaccharide (LPS)
Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The CCRE will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes).
| Study group | Role | What they receive |
|---|---|---|
| CCRE | Experimental | 20,000 EU of CCRE (Clinical Center Reference Endotoxin) Receives: Drug: CCRE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peripheral blood PMNs
The objective of this study is to identify endotoxin responders, characterized by an increase in post-CCRE peripheral blood polymorphonuclear (PMN)s compared to that day's baseline values of > 20%. Thus, there will be two data points for this cohort, blood PMNs at baseline and PMNs 6 hours following 20,000 endotoxin units (EU) of CCRE.
Measured: 6 hrs post exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study start11 Dec 2017
- Primary completion6 Aug 2019
- Study completion6 Aug 2019
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.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Responsible party
- Sponsor
- Investigators
- Michelle Hernandez, MD, Principal investigator, UNC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02847247
- Sponsor's protocol ID
- 15-1458
- Acronym
- Endoscreen
- Status last verified
- Sep 2019
- First submitted
- 25 Jul 2016
- Last updated
- 20 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: for internal analysis only
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Inflammatory Response to 20,000 EU Clinical Center Reference Endotoxin in Normal Adults
- ClinicalTrials.gov ID
- NCT02847247
- Acronym / sponsor ID
- Endoscreen / 15-1458
- Conditions
- Healthy
- Keywords
- healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Study start
- 11 Dec 2017 (actual)
- Primary completion
- 6 Aug 2019 (actual)
- Study completion
- 6 Aug 2019 (actual)
- First posted
- 28 Jul 2016 (estimated)
- 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.
Purpose: The purpose of this study is to classify volunteers as endotoxin-responders or non-responders following inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE). Endotoxin is a commonly encountered bioaerosol and component of indoor and outdoor air pollution. For reasons that remain unclear, some individuals appear to be more susceptible to the inflammatory effects of inhaled endotoxin than are others, possibly owing to single nucleotide polymorphisms in the Toll-like receptor 4 (TLR4) gene that influence TLR4 signaling and function. These susceptible individuals represent a population of particular interest for further mechanistic studies of the effects of endotoxin and for therapeutic trials. Susceptibility to inhaled endotoxin will be determined by measuring change in peripheral blood neutrophil counts, a biomarker of systemic inflammation, following inhaled CCRE. In our previous work, the investigators have found that inhalation of 20,000 EU CCRE is well tolerated and induces measurable increase in neutrophil content of peripheral blood in susceptible individuals. Our hope is that this CCRE inhalation protocol can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin.
Detailed description
This is a single center, screening study involving recruitment of 18 normal volunteers (NV). The protocol is powered to compare absolute neutrophil count (ANC) in the blood 6 hours after inhalational challenge with CCRE compared baseline. In addition, as secondary endpoints, the investigators will evaluate inflammatory cytokine levels in systemic circulation and access for the presence of genes thought to be related to endotoxin response. Visits will be conducted by a study coordinator or other study staff, physical exams will be performed by the PI or other study physician.
Eighteen subjects will be recruited. There will be no gender or ethnic restrictions, and subjects will be healthy volunteers. Prior to enrollment in this study, subjects will have participated in our protocol 98-0799 (screening and database study for the CEMALB). Data such as medical history and allergy skin testing collected during the screening protocol will be included with data in this study. Subjects with positive allergy skin testing will not be excluded. Spirometry will be performed to determine the current level of lung function.
In order to identify those individuals who appear more susceptible to the systemic inflammatory effects of endotoxin exposure, subjects will undergo inhaled endotoxin challenge at the baseline visit followed 6 hours later by blood draw for complete blood count with differential to allow for calculation of absolute neutrophil count (ANC). Subjects will be considered "responders" if their peripheral ANC increases by at least 20% following inhaled endotoxin challenge.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CCRE | Experimental | Drug: CCRE20,000 EU of CCRE (Clinical Center Reference Endotoxin) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subjects must be 18-50 years of age to be eligible for study participation
- Subjects must be willing to and able to provide informed consent and participate in all study procedures
- Normal lung function, defined as (Knudson 1976/1984 predicted set):
- Oxygen saturation of > 94% Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
- Symptom Score (defined in section "f") no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.
Key exclusion criteria (15 listed)
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
- Physician directed emergency treatment for asthma exacerbation within the preceding 3 months.
- Moderate or Severe asthma
- Exacerbation of asthma more than 2x/week that would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
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 |
|---|---|---|
| CCREAlso: endotoxin, lipopolysaccharide (LPS)Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The CCRE will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes). | Drug | CCRE |
Primary outcome
Change in peripheral blood PMNs
Time frame: 6 hrs post exposure
The objective of this study is to identify endotoxin responders, characterized by an increase in post-CCRE peripheral blood polymorphonuclear (PMN)s compared to that day's baseline values of > 20%. Thus, there will be two data points for this cohort, blood PMNs at baseline and PMNs 6 hours following 20,000 endotoxin units (EU) of CCRE.
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 20 Sep 2019.
- Individual participant dataSharing planned: No. for internal analysis only
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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.
Michelle Hernandez, MD principal investigator
UNC
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 CCRE in people with Healthy, run by University of North Carolina, Chapel Hill 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 8 inclusion and 15 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 20 Sep 2019. 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. 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?
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?
Change in peripheral blood PMNs (time frame: 6 hrs post exposure). 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 20 Sep 2019.