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出境医 / 临床实验 / The Role of the Immune and Inflammatory Systems in Hypertension

The Role of the Immune and Inflammatory Systems in Hypertension

Study Description
Brief Summary:
To define the cytokine and cellular immune signature of primary hypertension. Cross sectional clinical/laboratory study.

Condition or disease Intervention/treatment
Hypertension Inflammation Vascular Diseases Other: None involved

Detailed Description:

Experimental data show the presence of immune and inflammatory systems dysregulation in hypertension. Understanding of the inflammatory and immune nature of hypertension is currently based on studies in rodent models of hypertension, but is supported by human epidemiological and genome wide association studies (GWAS) studies. It is now essential to identify key checkpoints and inflammatory mechanism(s) involved in human hypertension in comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth hypothesis-driven mechanistic studies. This approach may provide the basis for future randomized clinical trials (RCTs).

To define the relationships and predictive value of the immune signature of hypertension and clinical phenotypes of hypertension :

  • Predictive value of immune signature for blood pressure parameters measured by ambulatory blood pressure measurements (ABPM)
  • Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow mediated dilatation (FMD) both complementary non-invasive techniques.
  • Predictive value of immune signature for vascular stiffness and central pressure assessed by SphygmoCor
  • Predictive value of immune signature for renal function parameters
  • Predictive value of immune signature for cognitive function. To define genetic determinants of immune signature of hypertension.
Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Study of the Roles of the Immune and Inflammatory Systems in Hypertension
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2021
Arms and Interventions
Group/Cohort Intervention/treatment
Study group

80 with hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring.

Clinical and laboratory assessment. NO intervention.

Other: None involved
NO intervention

Control

80 WITHOUT hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring.

Clinical and laboratory assessment. NO intervention.

Other: None involved
NO intervention

Outcome Measures
Primary Outcome Measures :
  1. cellular immune signature of primary hypertension: flow cytometry quantification of peripheral blood monocyte subtypes [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    measuring expression of B cells markers, T cell markers, and DC cell markers

  2. demographics: blood pressure [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    systolic and diastolic; office and ambulatory; in mmHG

  3. demographics: BMI [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    in kg/m^2; calculated from height in meters and weight in kg


Secondary Outcome Measures :
  1. Endo-PAT2000 "hyperaemia index" [ Time Frame: until total number recruited or end of study period (June 2021) ]

    As a measure of endothelial function: measuring Peripheral Arterial Tone (PAT) signal changes to a reactive hyperemia challenge. The PAT signal is a measure of the digital pulsatile volume. The expected response is of a post occlusion increase of the PAT signal amplitude. PAT score is provided automatically by the system's software and is basically the ratio between the post- to pre- occlusion average signal size, corrected for systemic changes and baseline level.

    changes


  2. flow mediated dilatation (FMD) (percent) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    as a measure of endothelial function

  3. carotid intimal media thickness (mm) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure

  4. assessed by SphygmoCor (meters/second) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure

  5. serum Creatinine (mMol/L) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of renal function

  6. "International Physical Activity Questionnaire" (score) [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of physical activity. From hours of sedentary time, mild/moderate/vigorous activity over a week, it then calculates METs/week.

  7. Interheart Diet Questionnaire score [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of health and activity. Based on known risk factors ie smoking diabetes, family history, dietary factors. Used as a validated measure of cardiovascular risk; score from 0 (minimal risk) to 48 (high risk)


Biospecimen Retention:   Samples With DNA
Blood for flow cytometry. Blood and urine for biomarker analysis. Blood for possible RNA analysis

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Otherwise fit and healthy individuals with hypertension who are treatment naive.
Criteria

Inclusion Criteria:

  • Age between 18-55 years
  • Cases: Office blood pressure ≥140 and ≥90
  • Controls: Office blood pressure <140 and <90 and age, sex and BMI matching to cases

Exclusion Criteria:

  • Age >55 years old;
  • Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid disease)
  • Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks;
  • hospitalization within the past 3 months;
  • Life expectancy of < 3 years;
  • History of alcohol/substance abuse
  • Inflammatory conditions e.g. Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; pericardial or pleural effusion, ascites; liver disease;
  • Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's disease; non-basal cell malignancy or myelo- or lymphoproliferative disease within the past 5 years; known HIV+; Immunizations (3 months); pulmonary hypertension;
  • Pregnancy, nursing;
  • History of symptomatic coronary artery disease (events) or heart failure;
  • BMI>40,
  • diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);
  • Known albuminuria/microalbuminuria;
  • GFR<60mL/min/1.73m2.
  • Any chronic concurrent treatment: Use of systemic or local steroids/immunosuppressive agents (within 6 months) of the inclusion; Current (within past 3 months) use of anti-hypertensive medication;
  • Major depressive illness or other psychiatric conditions.
  • Participants who decline participation in the study or who are unable to provide informed consent
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Eleanor Murray, MBChB 0141 232 7600 cams-ins-inflammatension@glasgow.ac.uk
Contact: Tomasz Guzik, Prof tomasz.guzik@glasgow.ac.uk

Locations
Layout table for location information
United Kingdom
Clinical Research Facility Recruiting
Glasgow, City Of Glasgow, United Kingdom, G51 4LB
Contact: tomasz guzik    0141 3307590    cams-ins-inflammatension@glasgow.ac.uk   
Contact: Joanne Flynn    0141 232 7600    joanne.flynn@ggc.scot.nhs.uk   
Principal Investigator: eleanor c murray         
Sponsors and Collaborators
University of Glasgow
European Research Council
Tracking Information
First Submitted Date April 30, 2019
First Posted Date July 11, 2019
Last Update Posted Date May 14, 2021
Actual Study Start Date May 7, 2019
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 10, 2019)
  • cellular immune signature of primary hypertension: flow cytometry quantification of peripheral blood monocyte subtypes [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    measuring expression of B cells markers, T cell markers, and DC cell markers
  • demographics: blood pressure [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    systolic and diastolic; office and ambulatory; in mmHG
  • demographics: BMI [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    in kg/m^2; calculated from height in meters and weight in kg
Original Primary Outcome Measures
 (submitted: July 8, 2019)
  • cellular immune signature of primary hypertension: flow cytometry quantification of peripheral blood monocyte subtypes [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    measuring expression of B cells markers, T cell markers, and DC cell markers
  • demographics: blood pressure [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    office and ambulatory; in mmHG
  • demographics: BMI [ Time Frame: rolling analysis until total number recruited or end of study period (June 2021) ]
    in kg/m^2; calculated from height in meters and weight in kg
Change History
Current Secondary Outcome Measures
 (submitted: July 10, 2019)
  • Endo-PAT2000 "hyperaemia index" [ Time Frame: until total number recruited or end of study period (June 2021) ]
    As a measure of endothelial function: measuring Peripheral Arterial Tone (PAT) signal changes to a reactive hyperemia challenge. The PAT signal is a measure of the digital pulsatile volume. The expected response is of a post occlusion increase of the PAT signal amplitude. PAT score is provided automatically by the system's software and is basically the ratio between the post- to pre- occlusion average signal size, corrected for systemic changes and baseline level. changes
  • flow mediated dilatation (FMD) (percent) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    as a measure of endothelial function
  • carotid intimal media thickness (mm) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure
  • assessed by SphygmoCor (meters/second) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure
  • serum Creatinine (mMol/L) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of renal function
  • "International Physical Activity Questionnaire" (score) [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of physical activity. From hours of sedentary time, mild/moderate/vigorous activity over a week, it then calculates METs/week.
  • Interheart Diet Questionnaire score [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of health and activity. Based on known risk factors ie smoking diabetes, family history, dietary factors. Used as a validated measure of cardiovascular risk; score from 0 (minimal risk) to 48 (high risk)
Original Secondary Outcome Measures
 (submitted: July 8, 2019)
  • Endo-PAT2000 "hyperaemia index" [ Time Frame: until total number recruited or end of study period (June 2021) ]
    As a measure of endothelial function
  • flow mediated dilatation (FMD) (percent) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    as a measure of endothelial function
  • carotid intimal media thickness (mm) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure
  • assessed by SphygmoCor (meters/second) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of vascular stiffness and central pressure
  • serum Creatinine (mMol/L) [ Time Frame: until total number recruited or end of study period (June 2021) ]
    measure of renal function
  • International Physical Activity Questionnaire (score) [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of health and acitivty
  • Interheart Diet Questionnaire score [ Time Frame: until end of study period (June 2021) ]
    Questionnaire measures of health and acitivty
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title The Role of the Immune and Inflammatory Systems in Hypertension
Official Title A Study of the Roles of the Immune and Inflammatory Systems in Hypertension
Brief Summary To define the cytokine and cellular immune signature of primary hypertension. Cross sectional clinical/laboratory study.
Detailed Description

Experimental data show the presence of immune and inflammatory systems dysregulation in hypertension. Understanding of the inflammatory and immune nature of hypertension is currently based on studies in rodent models of hypertension, but is supported by human epidemiological and genome wide association studies (GWAS) studies. It is now essential to identify key checkpoints and inflammatory mechanism(s) involved in human hypertension in comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth hypothesis-driven mechanistic studies. This approach may provide the basis for future randomized clinical trials (RCTs).

To define the relationships and predictive value of the immune signature of hypertension and clinical phenotypes of hypertension :

  • Predictive value of immune signature for blood pressure parameters measured by ambulatory blood pressure measurements (ABPM)
  • Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow mediated dilatation (FMD) both complementary non-invasive techniques.
  • Predictive value of immune signature for vascular stiffness and central pressure assessed by SphygmoCor
  • Predictive value of immune signature for renal function parameters
  • Predictive value of immune signature for cognitive function. To define genetic determinants of immune signature of hypertension.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood for flow cytometry. Blood and urine for biomarker analysis. Blood for possible RNA analysis
Sampling Method Non-Probability Sample
Study Population Otherwise fit and healthy individuals with hypertension who are treatment naive.
Condition
  • Hypertension
  • Inflammation
  • Vascular Diseases
Intervention Other: None involved
NO intervention
Study Groups/Cohorts
  • Study group

    80 with hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring.

    Clinical and laboratory assessment. NO intervention.

    Intervention: Other: None involved
  • Control

    80 WITHOUT hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring.

    Clinical and laboratory assessment. NO intervention.

    Intervention: Other: None involved
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 12, 2021)
160
Original Estimated Enrollment
 (submitted: July 8, 2019)
240
Estimated Study Completion Date September 1, 2021
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age between 18-55 years
  • Cases: Office blood pressure ≥140 and ≥90
  • Controls: Office blood pressure <140 and <90 and age, sex and BMI matching to cases

Exclusion Criteria:

  • Age >55 years old;
  • Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid disease)
  • Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks;
  • hospitalization within the past 3 months;
  • Life expectancy of < 3 years;
  • History of alcohol/substance abuse
  • Inflammatory conditions e.g. Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; pericardial or pleural effusion, ascites; liver disease;
  • Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's disease; non-basal cell malignancy or myelo- or lymphoproliferative disease within the past 5 years; known HIV+; Immunizations (3 months); pulmonary hypertension;
  • Pregnancy, nursing;
  • History of symptomatic coronary artery disease (events) or heart failure;
  • BMI>40,
  • diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);
  • Known albuminuria/microalbuminuria;
  • GFR<60mL/min/1.73m2.
  • Any chronic concurrent treatment: Use of systemic or local steroids/immunosuppressive agents (within 6 months) of the inclusion; Current (within past 3 months) use of anti-hypertensive medication;
  • Major depressive illness or other psychiatric conditions.
  • Participants who decline participation in the study or who are unable to provide informed consent
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Eleanor Murray, MBChB 0141 232 7600 cams-ins-inflammatension@glasgow.ac.uk
Contact: Tomasz Guzik, Prof tomasz.guzik@glasgow.ac.uk
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT04015635
Other Study ID Numbers 300798-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party TOMASZ GUZIK, University of Glasgow
Study Sponsor University of Glasgow
Collaborators European Research Council
Investigators Not Provided
PRS Account University of Glasgow
Verification Date May 2021