InflammationEarly Phase 1RESOLVE-SEXNCT05597098
Investigation of the Distinct Mechanisms Involved in Inflammatory Resolution Between Healthy Men and Women
A Early Phase 1 study testing Cantharidin in people with Inflammation, run by Queen Mary University of London at 1 site in United Kingdom.
Trial summary
Important differences exist between sexes in incidence, disease patterns and outcomes in coronary artery disease that is not well understood. It is likely that key differences in the underlying biological mechanism, in particular in inflammatory responses, play a part in underpinning these differences. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation
- What is being tested?
- Cantharidin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Dec 2022to 12 Dec 2027
- Phase
- Early 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male and female volunteers
- Aged 18-45
- Volunteers who are willing to sign the consent form
Who cannot join
- Healthy subjects unwilling to consent
- Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
- Current breast feeding
- History of any serious illnesses, including recent infections or trauma
- Subjects taking systemic medication (other than the oral contraceptive pill)
- Subjects with recent (2 weeks) or current antibiotic use
- Subjects with any history of a blood-borne infectious disease such as Hepatitis B or C virus, or HIV
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The William Harvey Research Institute
London, EC1M 6BQ
About this study
Official title: Investigation of the Distinct Mechanisms Involved in Inflammatory Resolution Between Healthy Men and Women: RESOLVE-SEX
Important differences exist between sexes in incidence, disease patterns and outcomes in coronary artery disease that is not well understood. It is likely that key differences in the underlying biological mechanism, in particular in inflammatory responses, play a part in underpinning these differences. Previous evidence demonstrates that healthy females appear to be more adept at resolving inflammation compared to healthy males. Since inflammation is thought to be a key initiating phenomenon in coronary artery disease the investigators will examine the differences in inflammatory resolution between the sexes in healthy volunteers.
Read the detailed description
Inflammation is a key process in triggering events caused by coronary artery disease. Indeed, large scale trials have tested the efficacy of a range of anti-inflammatory approaches. However, whilst some of these confirmed the utility of such approaches in leading to reductions in coronary artery disease; the benefits came at a cost with an increased risk of infection. In their previous work the investigators discovered that, women demonstrate enhanced resolution of inflammation compared to males. This accelerated resolution coincided with improved blood vessel function and health. It is also now accepted that a failure of resolution plays an important part in the enhanced inflammation seen in coronary artery disease. Whether the differences in the incidence of coronary artery disease between men and women might be related to differences in their capacity to mount a resolution response is unknown.
To determine whether inflammatory resolution differs between sexes the investigators will use the validated cantharidin-induced model of acute inflammation in healthy volunteers. Previous published studies have shown when cantharidin is applied to the skin it causes acantholysis and blister formation. It is a safe, reproducible technique with no permanent scarring or ill-effects. The investigators will study the effects on inflammatory responses by measuring the levels of cells, inflammatory mediators and markers of vascular function in blister fluid, urine, saliva and blood. Cantharidin application will be applied to separate areas of the skin over the course of three days to create three small blisters in order to examine different timepoints of the inflammatory process. The blister fluid will then be collected on the fourth day which will be analysed according to standard laboratory techniques including flow cytometry.
- Conditions
- Inflammation
- Being tested
- Cantharidin
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CantharidinDrug
Also called Cantharone 0.1%
0.1% cantharidin solution in acetone from 0.7% stock solution of cantharone is prepared and applied immediately. 10 μl of cantharidin per disc.
| Study group | Role | What they receive |
|---|---|---|
| Female | Experimental | The participant will initially attend either in person or virtually for a screening visit for eligibility. Cantharidin will be applied on the second visit to the forearm, back or abdomen (depending on patient preference) via 1cm2 cantharidin soaked filter paper. The particpant will then attend for two further cantharidin applications (24 hr and 48 hr after the first application). 72 hours after initial cantharidin application the blister fluid will be collected. Receives: Drug: Cantharidin |
| Male | Experimental | The participant will initially attend either in person or virtually for a screening visit for eligibility. Cantharidin will be applied on the second visit to the forearm, back or abdomen (depending on patient preference) via 1cm2 cantharidin soaked filter paper. The particpant will then attend for two further cantharidin applications (24 hr and 48 hr after the first application). 72 hours after initial cantharidin application the blister fluid will be collected. Receives: Drug: Cantharidin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the presence or not of blister at each timepoint over 24-72h between the sexes
Visual inspection as to the presence of an intact blister of 24hr, 48 hr and 72 hr cantharidin blisters
Measured: 24 hours, 48 hours, 72 hours
Comparison of blister volume at each timepoint over 24-72h between the sexes
Blister fluid sampled and weighed to determine volume
Measured: 24 hours, 48 hours, 72 hours
Comparison of blister cell number at each timepoint over 24-72 hours between the sexes
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Fluid will be analysed using standard laboratory techniques including labelled flow cytometry
Measured: 24 hours, 48 hours, 72 hours
Secondary outcomes (4)
Comparison of blister leukocyte subsets (neutrophil and monocyte) between the sexes at each timepoint
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Fluid will be analysed using standard laboratory techniques including labelled flow cytometry
Measured: 24 hours, 48 hours, 72 hours
Comparison of blister lactate levels and LDH between the sexes at each timepoint
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Analysis as per standard laboratory techniques.
Measured: 24 hours, 48 hours, 72 hours
Comparison of cell death, necrotic, and apoptotic cell numbers between the sexes at each timepoint
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Fluid will be analysed using standard laboratory techniques including labelled flow cytometry
Measured: 24 hours, 48 hours, 72 hours
4. Comparison of markers of blister efferocytosis between the sexes at each timepoint
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Fluid will be analysed using standard laboratory techniques including labelled flow cytometry
Measured: 24 hours, 48 hours, 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2022
- Study start12 Dec 2022
- Primary completion12 Dec 2027 (estimated)
- Study completion12 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amrita Ahluwalia, BSc PhD, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05597098
- Sponsor's protocol ID
- 22/YH/0244
- Acronym
- RESOLVE-SEX
- Status last verified
- Jul 2026
- First submitted
- 24 Oct 2022
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shabbir A, Rathod KS, Khambata RS, Ahluwalia A. Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease. Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:333-359. doi: 10.1146/annurev-pharmtox-010919-023229. Epub 2020 Oct 9.
PubMed 33035428Docherty JR, Stanford SC, Panattieri RA, Alexander SPH, Cirino G, George CH, Hoyer D, Izzo AA, Ji Y, Lilley E, Sobey CG, Stanley P, Stefanska B, Stephens G, Teixeira M, Ahluwalia A. Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable. Br J Pharmacol. 2019 Nov;176(21):4081-4086. doi: 10.1111/bph.14761. Epub 2019 Aug 23. No abstract available.
PubMed 31441038Rathod KS, Jones DA, Jain AK, Lim P, MacCarthy PA, Rakhit R, Lockie T, Kalra S, Dalby MC, Malik IS, Whitbread M, Firoozi S, Bogle R, Redwood S, Cooper J, Gupta A, Lansky A, Wragg A, Mathur A, Ahluwalia A. The influence of biological age and sex on long-term outcome after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiovasc Dis. 2021 Oct 25;11(5):659-678. eCollection 2021.
PubMed 34849299Kapil V, Rathod KS, Khambata RS, Bahra M, Velmurugan S, Purba A, S Watson D, Barnes MR, Wade WG, Ahluwalia A. Sex differences in the nitrate-nitrite-NO* pathway: Role of oral nitrate-reducing bacteria. Free Radic Biol Med. 2018 Oct;126:113-121. doi: 10.1016/j.freeradbiomed.2018.07.010. Epub 2018 Jul 20.
PubMed 30031863Rathod KS, Kapil V, Velmurugan S, Khambata RS, Siddique U, Khan S, Van Eijl S, Gee LC, Bansal J, Pitrola K, Shaw C, D'Acquisto F, Colas RA, Marelli-Berg F, Dalli J, Ahluwalia A. Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans. J Clin Invest. 2017 Jan 3;127(1):169-182. doi: 10.1172/JCI89429. Epub 2016 Nov 28.
PubMed 27893465
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Distinct Mechanisms Involved in Inflammatory Resolution Between Healthy Men and Women: RESOLVE-SEX
- ClinicalTrials.gov ID
- NCT05597098
- Acronym / sponsor ID
- RESOLVE-SEX / 22/YH/0244
- Conditions
- Inflammation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 12 Dec 2022 (actual)
- Primary completion
- 12 Dec 2027 (estimated)
- Study completion
- 12 Dec 2027 (estimated)
- First posted
- 27 Oct 2022 (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.
Important differences exist between sexes in incidence, disease patterns and outcomes in coronary artery disease that is not well understood. It is likely that key differences in the underlying biological mechanism, in particular in inflammatory responses, play a part in underpinning these differences. Previous evidence demonstrates that healthy females appear to be more adept at resolving inflammation compared to healthy males. Since inflammation is thought to be a key initiating phenomenon in coronary artery disease the investigators will examine the differences in inflammatory resolution between the sexes in healthy volunteers.
Detailed description
Inflammation is a key process in triggering events caused by coronary artery disease. Indeed, large scale trials have tested the efficacy of a range of anti-inflammatory approaches. However, whilst some of these confirmed the utility of such approaches in leading to reductions in coronary artery disease; the benefits came at a cost with an increased risk of infection. In their previous work the investigators discovered that, women demonstrate enhanced resolution of inflammation compared to males. This accelerated resolution coincided with improved blood vessel function and health. It is also now accepted that a failure of resolution plays an important part in the enhanced inflammation seen in coronary artery disease. Whether the differences in the incidence of coronary artery disease between men and women might be related to differences in their capacity to mount a resolution response is unknown.
To determine whether inflammatory resolution differs between sexes the investigators will use the validated cantharidin-induced model of acute inflammation in healthy volunteers. Previous published studies have shown when cantharidin is applied to the skin it causes acantholysis and blister formation. It is a safe, reproducible technique with no permanent scarring or ill-effects. The investigators will study the effects on inflammatory responses by measuring the levels of cells, inflammatory mediators and markers of vascular function in blister fluid, urine, saliva and blood. Cantharidin application will be applied to separate areas of the skin over the course of three days to create three small blisters in order to examine different timepoints of the inflammatory process. The blister fluid will then be collected on the fourth day which will be analysed according to standard laboratory techniques including flow cytometry.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Female | Experimental | Drug: CantharidinThe participant will initially attend either in person or virtually for a screening visit for eligibility. Cantharidin will be applied on the second visit to the forearm, back or abdomen (depending on patient preference) via 1cm2 cantharidin soaked filter paper. The particpant will then attend for two further cantharidin applications (24 hr and 48 hr after the first application). 72 hours after initial cantharidin application the blister fluid will be collected. |
| Male | Experimental | Drug: CantharidinThe participant will initially attend either in person or virtually for a screening visit for eligibility. Cantharidin will be applied on the second visit to the forearm, back or abdomen (depending on patient preference) via 1cm2 cantharidin soaked filter paper. The particpant will then attend for two further cantharidin applications (24 hr and 48 hr after the first application). 72 hours after initial cantharidin application the blister fluid will be collected. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy male and female volunteers
- Aged 18-45
- Volunteers who are willing to sign the consent form
Key exclusion criteria (7 listed)
- Healthy subjects unwilling to consent
- Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
- Current breast feeding
- History of any serious illnesses, including recent infections or trauma
- Subjects taking systemic medication (other than the oral contraceptive pill)
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 |
|---|---|---|
| CantharidinAlso: Cantharone 0.1%0.1% cantharidin solution in acetone from 0.7% stock solution of cantharone is prepared and applied immediately. 10 μl of cantharidin per disc. | Drug | Female, Male |
Primary outcome
Comparison of the presence or not of blister at each timepoint over 24-72h between the sexes
Time frame: 24 hours, 48 hours, 72 hours
Visual inspection as to the presence of an intact blister of 24hr, 48 hr and 72 hr cantharidin blisters
Comparison of blister volume at each timepoint over 24-72h between the sexes
Time frame: 24 hours, 48 hours, 72 hours
Blister fluid sampled and weighed to determine volume
Comparison of blister cell number at each timepoint over 24-72 hours between the sexes
Time frame: 24 hours, 48 hours, 72 hours
Blister fluid collected from 24 hour, 48 hour and 72 hour cantharidin blisters. Fluid will be analysed using standard laboratory techniques including labelled flow cytometry
4 secondary outcomes
Comparison of blister leukocyte subsets (neutrophil and monocyte) between the sexes at each timepoint
Time frame: 24 hours, 48 hours, 72 hours
Comparison of blister lactate levels and LDH between the sexes at each timepoint
Time frame: 24 hours, 48 hours, 72 hours
Comparison of cell death, necrotic, and apoptotic cell numbers between the sexes at each timepoint
Time frame: 24 hours, 48 hours, 72 hours
4. Comparison of markers of blister efferocytosis between the sexes at each timepoint
Time frame: 24 hours, 48 hours, 72 hours
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 16 Jul 2026.
- Background: PubMed 33035428Shabbir A, Rathod KS, Khambata RS, Ahluwalia A. Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease. Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:333-359. doi: 10.1146/annurev-pharmtox-010919-023229. Epub 2020 Oct 9.
- Background: PubMed 31441038Docherty JR, Stanford SC, Panattieri RA, Alexander SPH, Cirino G, George CH, Hoyer D, Izzo AA, Ji Y, Lilley E, Sobey CG, Stanley P, Stefanska B, Stephens G, Teixeira M, Ahluwalia A. Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable. Br J Pharmacol. 2019 Nov;176(21):4081-4086. doi: 10.1111/bph.14761. Epub 2019 Aug 23. No abstract available.
- Results publication: PubMed 34849299Rathod KS, Jones DA, Jain AK, Lim P, MacCarthy PA, Rakhit R, Lockie T, Kalra S, Dalby MC, Malik IS, Whitbread M, Firoozi S, Bogle R, Redwood S, Cooper J, Gupta A, Lansky A, Wragg A, Mathur A, Ahluwalia A. The influence of biological age and sex on long-term outcome after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiovasc Dis. 2021 Oct 25;11(5):659-678. eCollection 2021.
- Results publication: PubMed 30031863Kapil V, Rathod KS, Khambata RS, Bahra M, Velmurugan S, Purba A, S Watson D, Barnes MR, Wade WG, Ahluwalia A. Sex differences in the nitrate-nitrite-NO* pathway: Role of oral nitrate-reducing bacteria. Free Radic Biol Med. 2018 Oct;126:113-121. doi: 10.1016/j.freeradbiomed.2018.07.010. Epub 2018 Jul 20.
- Results publication: PubMed 27893465Rathod KS, Kapil V, Velmurugan S, Khambata RS, Siddique U, Khan S, Van Eijl S, Gee LC, Bansal J, Pitrola K, Shaw C, D'Acquisto F, Colas RA, Marelli-Berg F, Dalli J, Ahluwalia A. Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans. J Clin Invest. 2017 Jan 3;127(1):169-182. doi: 10.1172/JCI89429. Epub 2016 Nov 28.
- Individual participant dataSharing planned: No
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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.
Amrita Ahluwalia, BSc PhD principal investigator
Queen Mary University of London
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 Cantharidin in people with Inflammation, run by Queen Mary University of London at 1 site in United Kingdom.
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 3 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 16 Jul 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 Kingdom. 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?
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?
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?
Comparison of the presence or not of blister at each timepoint over 24-72h between the sexes (time frame: 24 hours, 48 hours, 72 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05597098, which also lists 5 linked publications.
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 16 Jul 2026.