Cardiovascular FunctionEarly Phase 1NCT01582321
Investigation of the Influence of Gender on Cardiovascular Function
A Early Phase 1 study testing Typhoid vaccine and Cantharidin in people with Cardiovascular Function, run by Queen Mary University of London at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Function
- What is being tested?
- Typhoid vaccine and Cantharidin
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2012to Jan 2017
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects aged 18-45 who have volunteered themselves and are willing to sign the consent form.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
William Harvey Heart Centre, Barts & The London Medical School
London, EC1M 6BQ
About this study
Official title: Investigation of the Influence of Gender on Cardiovascular Function and Inflammation
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.
Read the detailed description
We now know that one of the earliest events involved in precipitating disease of the heart and blood vessels is the phenomenon of inflammation and that this inflammation is a key process involved in dampening the protective nature of the inner lining (the endothelium) of the blood vessel wall, called endothelial dysfunction. In healthy arteries the endothelium releases a number of factors that maintain the health of the blood vessel. These factors act to keep the blood vessel in an open and dilated state and prevent the furring up of the vessel by actively inhibiting the cell components of the blood from collecting at the endothelium and blocking the flow of blood through the artery. Recent research in animals has demonstrated that one of the key components of inflammation i.e. the attraction of white cells, is reduced in females compared to males and that this is due to a reduced expression of key proteins called 'adhesion molecules', an in particular a molecule called P-selectin, on the endothelium. We now wish to determine whether similar differences in white cell attraction and adhesion molecules exist between the sexes in humans and whether these differences might underlie differences in endothelial function.
To investigate this possibility we will conduct a study in two parts, using well validated models of acute inflammation in healthy volunteers.
Part 1 To determine whether responses to inflammation differ between sexes in part 1 we will use a cantharidin-induced model of acute inflammation. 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. We will study the effects on inflammatory responses by measuring the levels of cells and inflammatory mediators in blister fluids, urine and plasma. Participants will given two blisters that will be harvested at 24 hours (acute phase) and 72 hours (resolution phase) after cantharidin application. The effects of inflammation on blood vessels will also be studied through non invasive blood pressure measurements.
Part 2 To determine whether susceptibility to inflammation-induced endothelial dysfunction is distinct between the sexes in part 2 we will use typhoid vaccine to induce mild inflammation throughout the body including the blood vessels. Previous published studies have shown that vaccination induces an acute inflammation that results in a temporary (reversed within 48h) dysfunction of the endothelium that can be measured using a range of non-invasive techniques called ultrasound flow-mediated dilatation and pulse wave velocity. We will use these techniques together with biochemical measurements to determine possible associations of endothelial dysfunction with specific inflammatory factors. In particular we will investigate the possibility that differences in the expression of the adhesion molecule P-selectin might have a role to play in differences between the sexes.
- Conditions
- Cardiovascular Function
- Being tested
- Typhoid vaccine, Cantharidin
- Keywords
- vascular ultrasound, flow cytometry, platelet aggregation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Typhoid vaccineBiological
Also called Typhim Vi®
The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution
CantharidinDrug
Also called Cantharidin, 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 |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Typhoid vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 0, 24, 48 h
Secondary outcomes (6)
Blood pressure (Part 1)
Blood pressure will be measured every 15 minutes for 1 hour
Measured: 0, 48, 72 h
Platelet reactivity (Part 2)
Blood will be collected and platelet reactivity assessed using impedance aggreometry
Measured: 0, 24 and 48h
Platelet activation (Part 2)
Blood will be collected and platelet p-selectin and platelet-monocyte expression determined using flow cytometry
Measured: 0,24 and 48h
Arterial stiffness (Part 2)
The speed of blood pressure waves will be measured to give a pulse wave velocity measure for the aorta.
Measured: 0, 24 and 48h
Inflammatory cell expression (Part 1 and 2)
Blood will be collected and inflammatory cell populations determined using flow cytometry
Measured: 0, 48, 72h part 1, 0, 24 and 48h part 2
Blood inflammatory molecule expression (Part 1 and 2)
Plasma will be collected for assessment of inflammatory markers
Measured: 0, 48, 72 h part 1, 0, 24 and 48h part 2,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study startMar 2012
- Primary completionDec 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular FunctionStudies 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
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amrita Ahluwalia, Queen Mary University of London
- Investigators
- Amrita Ahluwalia, BSC PhD, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01582321
- Sponsor's protocol ID
- 11/LO/2038
- Status last verified
- Jun 2017
- First submitted
- 18 Apr 2012
- Last updated
- 14 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 10961963Rathod 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 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Influence of Gender on Cardiovascular Function and Inflammation
- ClinicalTrials.gov ID
- NCT01582321
- Acronym / sponsor ID
- 11/LO/2038
- Conditions
- Cardiovascular Function
- Keywords
- vascular ultrasound, flow cytometry, platelet aggregation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Dec 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 20 Apr 2012 (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.
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.
Detailed description
We now know that one of the earliest events involved in precipitating disease of the heart and blood vessels is the phenomenon of inflammation and that this inflammation is a key process involved in dampening the protective nature of the inner lining (the endothelium) of the blood vessel wall, called endothelial dysfunction. In healthy arteries the endothelium releases a number of factors that maintain the health of the blood vessel. These factors act to keep the blood vessel in an open and dilated state and prevent the furring up of the vessel by actively inhibiting the cell components of the blood from collecting at the endothelium and blocking the flow of blood through the artery. Recent research in animals has demonstrated that one of the key components of inflammation i.e. the attraction of white cells, is reduced in females compared to males and that this is due to a reduced expression of key proteins called 'adhesion molecules', an in particular a molecule called P-selectin, on the endothelium. We now wish to determine whether similar differences in white cell attraction and adhesion molecules exist between the sexes in humans and whether these differences might underlie differences in endothelial function.
To investigate this possibility we will conduct a study in two parts, using well validated models of acute inflammation in healthy volunteers.
Part 1 To determine whether responses to inflammation differ between sexes in part 1 we will use a cantharidin-induced model of acute inflammation. 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. We will study the effects on inflammatory responses by measuring the levels of cells and inflammatory mediators in blister fluids, urine and plasma. Participants will given two blisters that will be harvested at 24 hours (acute phase) and 72 hours (resolution phase) after cantharidin application. The effects of inflammation on blood vessels will also be studied through non invasive blood pressure measurements.
Part 2 To determine whether susceptibility to inflammation-induced endothelial dysfunction is distinct between the sexes in part 2 we will use typhoid vaccine to induce mild inflammation throughout the body including the blood vessels. Previous published studies have shown that vaccination induces an acute inflammation that results in a temporary (reversed within 48h) dysfunction of the endothelium that can be measured using a range of non-invasive techniques called ultrasound flow-mediated dilatation and pulse wave velocity. We will use these techniques together with biochemical measurements to determine possible associations of endothelial dysfunction with specific inflammatory factors. In particular we will investigate the possibility that differences in the expression of the adhesion molecule P-selectin might have a role to play in differences between the sexes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 Male | Experimental | Drug: Cantharidin16 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. |
| Part 1 Female | Experimental | Drug: Cantharidin16 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. |
| Part 2 Male | Experimental | Biological: Typhoid vaccine12 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. |
| Part 2 Female | Experimental | Biological: Typhoid vaccine12 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy subjects aged 18-45 who have volunteered themselves and are willing to sign the consent form.
Key exclusion criteria (9 listed)
- 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)
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 |
|---|---|---|
| Typhoid vaccineAlso: Typhim Vi®The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution | Biological | Part 2 Female, Part 2 Male |
| CantharidinAlso: Cantharidin, 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 | Part 1 Female, Part 1 Male |
Primary outcome
Comparison change in blister fluid total and differential leukocyte numbers (Part 1)
Time frame: 24, 72 h
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
Flow-mediated dilatation (Part 2)
Time frame: 0, 24, 48 h
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.
6 secondary outcomes
Blood pressure (Part 1)
Time frame: 0, 48, 72 h
Platelet reactivity (Part 2)
Time frame: 0, 24 and 48h
Platelet activation (Part 2)
Time frame: 0,24 and 48h
Arterial stiffness (Part 2)
Time frame: 0, 24 and 48h
Inflammatory cell expression (Part 1 and 2)
Time frame: 0, 48, 72h part 1, 0, 24 and 48h part 2
Blood inflammatory molecule expression (Part 1 and 2)
Time frame: 0, 48, 72 h part 1, 0, 24 and 48h part 2,
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 14 Jun 2017.
- Background: PubMed 10961963Hingorani 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.
- Derived from this study: 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.
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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 Typhoid vaccine and Cantharidin in people with Cardiovascular Function, 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 1 inclusion and 9 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 14 Jun 2017. 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?
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?
Comparison change in blister fluid total and differential leukocyte numbers (Part 1) (time frame: 24, 72 h). The study lists 2 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 NCT01582321, which also lists 2 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 14 Jun 2017.