Investigation of the Influence of Gender on Cardiovascular Function

NCT01582321 | Completed Early Phase 1

• 1 other identifier: 11/LO/2038
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammation is a key initiating and damaging factor in many illnesses including infection, arthritis and cancer but also of particular relevance to this study in diseases of the heart and blood vessels (i.e. cardiovascular disease). Much evidence now exists demonstrating that male sex increases ones risk of cardiovascular disease. More recent evidence demonstrates that inflammatory responses in females appear to dampened in comparison to age matched males. Since inflammation is thought to be a key initiating phenomenon in many cardiovascular disease states the investigators will examine the differences in acute inflammatory responses between the sexes in healthy volunteers and the impact this has on the function of blood vessels.

Conditions

Cardiovascular Function

Keywords

vascular ultrasound; flow cytometry; platelet aggregation

Outcome Measures

Primary Outcomes (2)

• Comparison change in blister fluid total and differential leukocyte numbers (Part 1)

  plasma and fluid collected from the blisters at 24 hours (acute phase) and 72 hours (resolution phase) after the cantharidin application will be analysed using standard laboratory techniques including flow cytometry

  24, 72 h

• Flow-mediated dilatation (Part 2)

  Flow mediated dilatation of the brachial artery will be assessed using ultrasound will be measured at time 0, 24 and 48h. At the 16h timepoint a single typhoid vaccination will be administered in the arm or buttock.

  0, 24, 48 h

Secondary Outcomes (6)

• Blood pressure (Part 1)

  0, 48, 72 h

• Platelet reactivity (Part 2)

  0, 24 and 48h

• Platelet activation (Part 2)

  0,24 and 48h

• Arterial stiffness (Part 2)

  0, 24 and 48h

• Inflammatory cell expression (Part 1 and 2)

  0, 48, 72h part 1, 0, 24 and 48h part 2

Study Arms (4)

Part 1 Male

EXPERIMENTAL

16 healthy male volunteers will be recruited. Primary and secondary outcome measures will be made on day 1, 3 and 4. At 24 and 72 hours prior to outcome measures on day 3 a cantharidin-soaked 1cm2 filter paper disc will be applied to participants forearm or back on leg for blister formation. Blister fluids will be harvested on day 3.

Drug: Cantharidin

Part 1 Female

EXPERIMENTAL

16 healthy female volunteers will be recruited. Primary and secondary outcome measures will be made on day 1, 3 and 4. At 24 and 72 hours prior to outcome measures on day 3 a cantharidin-soaked 1cm2 filter paper disc will be applied to participants forearm or back on leg for blister formation. Blister fluids will be harvested on day 3.

Drug: Cantharidin

Part 2 Male

EXPERIMENTAL

12 healthy male volunteers will be recruited. Primary and secondary outcome measures will be made on day 0, 1 and 2. At 8 hours prior to outcome measures on day 1 intra-muscular typhoid vaccine will be administered.

Biological: Typhoid vaccine

Part 2 Female

EXPERIMENTAL

12 healthy female volunteers will be recruited. Primary and secondary outcome measures will be made on day 0, 1 and 2. At 8 hours prior to outcome measures on day 1 intra-muscular typhoid vaccine will be administered.

Biological: Typhoid vaccine

Interventions

Typhoid vaccine BIOLOGICAL

The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution

Also known as: Typhim Vi®

Part 2 Female; Part 2 Male

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: Cantharidin, cantharone 0.1%

Part 1 Female; Part 1 Male

Eligibility Criteria

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

You may qualify if:

• Healthy subjects aged 18-45 who have volunteered themselves and are willing to sign the consent form.

You may not qualify if:

• Healthy subjects unwilling to consent
• History of hypertension, diabetes or hypertensive on BP measurement
• Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
• History of any serious illnesses, including recent infections or trauma
• Subjects taking systemic medication (other than the oral contraceptive pill)
• Subjects with self-reported use of mouthwash or tongue scrapes
• Subjects with recent or current antibiotic use
• Subjects with a history, or recent treatment of (within last 3 months) of any oral condition (excluding caries), including gingivitis, periodontitis and halitosis.
• Subjects that have recently participated (preceding 3 months) in any clinical studies involving administration of an inflammogen.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

William Harvey Heart Centre, Barts & The London Medical School

London, EC1M 6BQ, United Kingdom

Location

Related Publications (2)

• Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, Donald AE, Palacios M, Griffin GE, Deanfield JE, MacAllister RJ, Vallance P. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation. 2000 Aug 29;102(9):994-9. doi: 10.1161/01.cir.102.9.994.

  PMID: 10961963 BACKGROUND

• 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 DERIVED

MeSH Terms

Interventions

Typhoid-Paratyphoid Vaccines; Vi polysaccharide vaccine, typhoid; Cantharidin

Intervention Hierarchy (Ancestors)

Salmonella Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Amrita Ahluwalia, BSC PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Vascular Pharmacology

Study Record Dates

• First Submitted: April 18, 2012
• First Posted: April 20, 2012
• Study Start: March 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

GB (1)