Inflammation; SkinEarly Phase 1NCT04308889
Pro-Resolving Mediators in Acute Inflammation in Humans
A Early Phase 1 study testing Lovaza, Cantharone and Phlebotomy in people with Inflammation; Skin and Resolution, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The investigators are undertaking a clinical blister model with or without dietary supplementation with omega-3 fatty acids (i.e., Lovaza) to determine the role of specialized pro-resolving mediators - endogenous lipids converted from omega-3 fatty acid precursors including those in Lovaza - on inflammation parameters… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation; Skin, Resolution, Blister
- What is being tested?
- Lovaza, Cantharone and Phlebotomy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2018to 22 Feb 2022
- 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 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults
- Ages 18-64
Who cannot join
- Known acute or chronic infection
- Known acute or chronic disease of any kind
- Known allergy to fish or shellfish
- Use of any prescription medication
- Use of over-the-counter medication except multivitamins
- Use of dietary or herbal supplement except protein supplements
Show all 16Show fewer
- Women that are pregnant, trying to become pregnant, or breastfeeding
- Any skin disease
- Known immunocompromise, HIV, or Diabetes mellitus
- History of cardiopulmonary disease
- History of upper extremity cellulitis
- Significant allergy of any kind
- Known bleeding diathesis
- History of keloid scar formation
- Forearm tattoo
- Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) during study or within 2 weeks prior to enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
The investigators are undertaking a clinical blister model with or without dietary supplementation with omega-3 fatty acids (i.e., Lovaza) to determine the role of specialized pro-resolving mediators - endogenous lipids converted from omega-3 fatty acid precursors including those in Lovaza - on inflammation parameters and their resolution.
Read the detailed description
The specific aims of this study are based on the hypothesis that in health, natural pro-resolving mechanisms, including specialized pro-resolving mediators and cellular effectors, are generated to promote the resolution of acute inflammation. The specific aims are:
Aim 1. Map the formation of specialized pro-resolving mediators and their relationship to acute tissue inflammation Aim 2. Determine the influence of omega-3 fatty acids on the formation and action of pro-resolving mediators during acute inflammation.
Medical history and clinical information will be obtained from the participant's health record for study purposes to be sure that participants meet the appropriate inclusion and exclusion criteria. The phlebotomy and topical application of the cantharidin, the imaging and clinical assessment and sampling of blister exudates will be performed by Dr. Katherine Walker or Dr. Joseph Merola and clinical study team at Brigham and Women's Hospital in the Building For Transformative Medicine (3rd floor, 60 Fenwood Road, Boston, MA). The biochemical, immunological and histological analyses will be performed in the laboratories of Drs. Bruce Levy and Charles Serhan at BWH in the Building For Transformative Medicine (3rd floor, 60 Fenwood Road).
The intervention protocol will involve simultaneous topical application of 12.5 mcl 0.1% cantharidin to two sites on the volar surface of one forearm. This dose is known to elicit a consistent, safe, localized reaction entailing redness (erythema), mild tenderness and warmth at the site, 2-3 cm in diameter. Subsequently, blister exudative fluid will be removed from each blister site, one during onset phase of inflammation (24 hrs after cantharidin) and the second during resolution phase (72 hrs after cantharidin). The blister exudates will be sampled by piercing the roof of the blister with a sterile needle to collect the exudate at designated time points. The site is disinfected prior to collection of the blister exudate and subsequently protected by a wound dressing after the sample collection step.
The intervention protocol will be performed twice for each participant, under 2 distinct conditions:
- without omega-3 fatty acid supplementation
- with omega-3 fatty acid supplementation: the participant will take 4 capsules (1gram each) of Lovaza daily at 8pm, starting the evening before blister induction and continuing until the second blister fluid has been removed.
This study is a crossover design to evaluate the production of pro-resolving mediators and resolution of experimental inflammation with and without additional omega-3 fatty acid supplementation, and to allow each subject to serve as an internal control by undergoing blister formation in both conditions. In order to reduce the influence of repeated cantharidin blister exposures on the outcome measurements, subjects will be randomized to start with either the Lovaza arm or the non-supplementation arm of the blister protocol.
- Conditions
- Inflammation; Skin, Resolution, Blister
- Being tested
- Lovaza, Cantharone, Phlebotomy
- Keywords
- Specialized pro-resolving mediators
- Medical subject headings
- Dermatitis, Blister
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LovazaDrug
Also called omega-3 fatty acid ethyl esters
Lovaza contains ethyl esters of omega-3 fatty acids (EPA and DHA) obtained from the oil of several fish sources.
CantharoneOther
Cantharone is a clinical blistering agent for topical use to remove warts and molluscum contagiosum. We plan to use the drug to elicit a small skin blister and inflammatory response. This is a well described clinical inflammation research experimental model with multiple publications of its safety and utility in tracking the host inflammatory response.
PhlebotomyOther
Subjects will have blood drawn from the antecubital vein for not more than 15mL at each visit.
| Study group | Role | What they receive |
|---|---|---|
| Without Supplementation | Active comparator | No planned dietary supplementation Receives: Other: Cantharone; Other: Phlebotomy |
| With Supplementation | Experimental | The subject will take 4 capsules (1gram each) of Lovaza daily at 8pm, starting the evening before blister induction and continuing until the second blister fluid has been removed. Receives: Drug: Lovaza; Other: Cantharone; Other: Phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Specialized Pro-Resolving Mediators in Acute Inflammation
Specialized Pro-Resolving Mediators (SPMs) in a participant's peripheral blood and blister fluid will be extracted and analyzed by targeted metabolo-lipidomics with liquid chromatography - tandem mass spectrometry to identify and quantify SPMs and related bioactive lipid mediators, namely leukotrienes and prostaglandins. Note that these fatty acids and bioactive mediators in blister exudates and peripheral blood will have the same units of measure.
Measured: 24 hours after blister induction
Secondary outcomes (4)
Inflammatory Cells in Acute Blister Exudates
Blister exudate fluid will be collected for determination of the presence of inflammatory cells by total cell count, and wright-giemsa staining of cytospins. Flow cytometry will be performed to confirm cell identity.
Measured: Change from 24 to 72 hours after blister induction
Inflammatory Cell Changes During Resolution of Acute Inflammation
Blister exudate fluid will be collected for determination of cell activation by flow cytometry, including SPM receptor expression and indicators of cell death.
Measured: Change from 24 to 72 hours after blister induction
Peripheral Blood Inflammatory Cells During Acute Inflammation and Resolution
Peripheral blood mononuclear cells will be analyzed by flow cytometry to determine activation markers, including SPM receptor expression.
Measured: Change from baseline to 24 hours and then to 72 hours after blister induction
Specialized Pro-Resolving Mediator Levels During Resolution of Acute Inflammation
Specialized Pro-Resolving Mediators (SPMs) in a participant's peripheral blood and blister fluid will be extracted and analyzed by targeted metabolo-lipidomics with liquid chromatography - tandem mass spectrometry to identify and quantify SPMs and related bioactive lipid mediators, namely leukotrienes and prostaglandins. Note that these fatty acids and bioactive mediators in blister exudates and peripheral blood will have the same units of measure.
Measured: Change from 24 hours to 72 hours after blister induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start2 Jul 2018
- Primary completion3 Feb 2022
- Study completion22 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammation; SkinStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Non-randomised
- Intervention model
- Crossover
- Model description
- Subjects will participate in a total of 6 study visits clustered into two groups of 3 visits (baseline, 24h and 72h after blister induction) for a total of 72 hours duration. The crossover for each group of 3 visits will be separated by at least 1 week.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Bruce D. Levy, Brigham and Women's Hospital
- Investigators
- Bruce D Levy, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308889
- Sponsor's protocol ID
- 2017P000836
- Other IDs
- 2P01GM095467-06
- Status last verified
- May 2022
- First submitted
- 10 Mar 2020
- Last updated
- 26 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The dissemination plan for the results of this study will include publication in peer-reviewed journals and presentation at scientific meetings. No IPD is planned for sharing with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pro-Resolving Mediators in Acute Inflammation in Humans
- ClinicalTrials.gov ID
- NCT04308889
- Acronym / sponsor ID
- 2017P000836
- Conditions
- Inflammation; Skin, Resolution, Blister
- Keywords
- Specialized pro-resolving mediators
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 2 Jul 2018 (actual)
- Primary completion
- 3 Feb 2022 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 16 Mar 2020 (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 investigators are undertaking a clinical blister model with or without dietary supplementation with omega-3 fatty acids (i.e., Lovaza) to determine the role of specialized pro-resolving mediators - endogenous lipids converted from omega-3 fatty acid precursors including those in Lovaza - on inflammation parameters and their resolution.
Detailed description
The specific aims of this study are based on the hypothesis that in health, natural pro-resolving mechanisms, including specialized pro-resolving mediators and cellular effectors, are generated to promote the resolution of acute inflammation. The specific aims are:
Aim 1. Map the formation of specialized pro-resolving mediators and their relationship to acute tissue inflammation Aim 2. Determine the influence of omega-3 fatty acids on the formation and action of pro-resolving mediators during acute inflammation.
Medical history and clinical information will be obtained from the participant's health record for study purposes to be sure that participants meet the appropriate inclusion and exclusion criteria. The phlebotomy and topical application of the cantharidin, the imaging and clinical assessment and sampling of blister exudates will be performed by Dr. Katherine Walker or Dr. Joseph Merola and clinical study team at Brigham and Women's Hospital in the Building For Transformative Medicine (3rd floor, 60 Fenwood Road, Boston, MA). The biochemical, immunological and histological analyses will be performed in the laboratories of Drs. Bruce Levy and Charles Serhan at BWH in the Building For Transformative Medicine (3rd floor, 60 Fenwood Road).
The intervention protocol will involve simultaneous topical application of 12.5 mcl 0.1% cantharidin to two sites on the volar surface of one forearm. This dose is known to elicit a consistent, safe, localized reaction entailing redness (erythema), mild tenderness and warmth at the site, 2-3 cm in diameter. Subsequently, blister exudative fluid will be removed from each blister site, one during onset phase of inflammation (24 hrs after cantharidin) and the second during resolution phase (72 hrs after cantharidin). The blister exudates will be sampled by piercing the roof of the blister with a sterile needle to collect the exudate at designated time points. The site is disinfected prior to collection of the blister exudate and subsequently protected by a wound dressing after the sample collection step.
The intervention protocol will be performed twice for each participant, under 2 distinct conditions:
- without omega-3 fatty acid supplementation
- with omega-3 fatty acid supplementation: the participant will take 4 capsules (1gram each) of Lovaza daily at 8pm, starting the evening before blister induction and continuing until the second blister fluid has been removed.
This study is a crossover design to evaluate the production of pro-resolving mediators and resolution of experimental inflammation with and without additional omega-3 fatty acid supplementation, and to allow each subject to serve as an internal control by undergoing blister formation in both conditions. In order to reduce the influence of repeated cantharidin blister exposures on the outcome measurements, subjects will be randomized to start with either the Lovaza arm or the non-supplementation arm of the blister protocol.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Subjects will participate in a total of 6 study visits clustered into two groups of 3 visits (baseline, 24h and 72h after blister induction) for a total of 72 hours duration. The crossover for each group of 3 visits will be separated by at least 1 week.
| Arm | Type | Receives |
|---|---|---|
| Without Supplementation | Active comparator | Other: Cantharone, Other: PhlebotomyNo planned dietary supplementation |
| With Supplementation | Experimental | Drug: Lovaza, Other: Cantharone, Other: PhlebotomyThe subject will take 4 capsules (1gram each) of Lovaza daily at 8pm, starting the evening before blister induction and continuing until the second blister fluid has been removed. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy adults
- Ages 18-64
Key exclusion criteria (16 listed)
- Known acute or chronic infection
- Known acute or chronic disease of any kind
- Known allergy to fish or shellfish
- Use of any prescription medication
- Use of over-the-counter medication except multivitamins
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 |
|---|---|---|
| LovazaAlso: omega-3 fatty acid ethyl estersLovaza contains ethyl esters of omega-3 fatty acids (EPA and DHA) obtained from the oil of several fish sources. | Drug | With Supplementation |
| CantharoneCantharone is a clinical blistering agent for topical use to remove warts and molluscum contagiosum. We plan to use the drug to elicit a small skin blister and inflammatory response. This is a well described clinical inflammation research experimental model with multiple publications of its safety and utility in tracking the host inflammatory response. | Other | With Supplementation, Without Supplementation |
| PhlebotomySubjects will have blood drawn from the antecubital vein for not more than 15mL at each visit. | Other | With Supplementation, Without Supplementation |
Primary outcome
Specialized Pro-Resolving Mediators in Acute Inflammation
Time frame: 24 hours after blister induction
Specialized Pro-Resolving Mediators (SPMs) in a participant's peripheral blood and blister fluid will be extracted and analyzed by targeted metabolo-lipidomics with liquid chromatography - tandem mass spectrometry to identify and quantify SPMs and related bioactive lipid mediators, namely leukotrienes and prostaglandins. Note that these fatty acids and bioactive mediators in blister exudates and peripheral blood will have the same units of measure.
4 secondary outcomes
Inflammatory Cells in Acute Blister Exudates
Time frame: Change from 24 to 72 hours after blister induction
Inflammatory Cell Changes During Resolution of Acute Inflammation
Time frame: Change from 24 to 72 hours after blister induction
Peripheral Blood Inflammatory Cells During Acute Inflammation and Resolution
Time frame: Change from baseline to 24 hours and then to 72 hours after blister induction
Specialized Pro-Resolving Mediator Levels During Resolution of Acute Inflammation
Time frame: Change from 24 hours to 72 hours after blister induction
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 26 May 2022.
- Individual participant dataSharing planned: No. The dissemination plan for the results of this study will include publication in peer-reviewed journals and presentation at scientific meetings. No IPD is planned for sharing with other researchers.
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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.
Bruce D Levy, MD principal investigator
Brigham and Women's Hospital
1 site 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 Lovaza, Cantharone and Phlebotomy in people with Inflammation; Skin and Resolution, run by Brigham and Women's Hospital 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 2 inclusion and 16 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 26 May 2022. 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?
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?
Specialized Pro-Resolving Mediators in Acute Inflammation (time frame: 24 hours after blister induction). 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 26 May 2022.