Investigation of the Distinct Mechanisms Involved in Inflammatory Resolution Between Healthy Men and Women

NCT05597098 | Recruiting Early Phase 1

• 1 other identifier: 22/YH/0244
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Inflammation

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  24 hours, 48 hours, 72 hours

Secondary Outcomes (4)

• Comparison of blister leukocyte subsets (neutrophil and monocyte) between the sexes at each timepoint

  24 hours, 48 hours, 72 hours

• Comparison of blister lactate levels and LDH between the sexes at each timepoint

  24 hours, 48 hours, 72 hours

• Comparison of cell death, necrotic, and apoptotic cell numbers between the sexes at each timepoint

  24 hours, 48 hours, 72 hours

• 4. Comparison of markers of blister efferocytosis between the sexes at each timepoint

  24 hours, 48 hours, 72 hours

Study Arms (2)

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.

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.

Drug: Cantharidin

Interventions

Cantharidin DRUG

0.1% cantharidin solution in acetone from 0.7% stock solution of cantharone is prepared and applied immediately. 10 μl of cantharidin per disc.

Also known as: Cantharone 0.1%

Female; Male

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female volunteers
• Aged 18-45
• Volunteers who are willing to sign the consent form

You may not qualify if:

• 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

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

The William Harvey Research Institute

London, EC1M 6BQ, United Kingdom

RECRUITING

Related Publications (5)

• 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.

  PMID: 33035428 BACKGROUND

• Docherty 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.

  PMID: 31441038 BACKGROUND

• Rathod 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.

  PMID: 34849299 RESULT

• Kapil 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.

  PMID: 30031863 RESULT

• Rathod 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.

  PMID: 27893465 RESULT

MeSH Terms

Conditions

Inflammation

Interventions

Cantharidin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Amrita Ahluwalia, BSc PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amrita Ahluwalia, BSc PhD

CONTACT

0207 882 8377; a.ahluwalia@qmul.ac.uk

Andrew J Sullivan, MBBS BSc

CONTACT

020 7882 8931; a.j.sullivan@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: October 27, 2022
• Study Start: December 12, 2022
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)