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Association Between Coronary Flow Reserve and BH4 Levels in High CV Risk

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ClinicalTrials.gov Identifier: NCT03841383
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Servier
Information provided by (Responsible Party):
Prof. Paolo G Camici MD FACC, IRCCS San Raffaele

Brief Summary:
To determine if there is a relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels in patients with high cardiovascular risk .

Condition or disease Intervention/treatment
Hypertension,Essential Diagnostic Test: Echo stress dipyridamole

Detailed Description:

Primary parameter :

relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels in patients with hypertension and concomitant cardiovascular risk factors.

Secondary parameter:

Levels of cGMP in platelets.

4. Study design

Three parallel groups of patients (n=15 per group):

  • Group 1 with normal coronary flow reserve (CFR ≥2.5)
  • Group 2 with reduced coronary flow reserve (CFR≤2.0)

    o Group 3 control subjects (without a high risk profile according to ESC score chart http://www.heartscore.org. ) matched for age (between 40 and 80 years of age)

  • and gender. 1/3 enrolled patients must be diabetic (Type2 diabetes)

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Study to Investigate the Association Between Coronary Flow Reserve and BH4 Levels in Patients With High Cardiovascular Risk
Actual Study Start Date : June 6, 2017
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : June 14, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Healthy controls Diagnostic Test: Echo stress dipyridamole
Echo stress dipyridamole
Other Name: Blood sample

Hypertensive patients Diagnostic Test: Echo stress dipyridamole
Echo stress dipyridamole
Other Name: Blood sample




Primary Outcome Measures :
  1. BH2 and BH4 levels (ng/ml) in plasma and platelets [ Time Frame: 1 week ]
    Blood samples will be withdrawn and subsequently analyzed to assess biopterins BH4 and BH2 ng/mL concentration in plasma and platelets Each will be determined separately from the same sample, by high-performance liquid chromatography followed by serial electrochemical and fluorescent detection.

  2. Coronary Flow Reserve (CFR) Trans Thoracic Doppler Echocardiography [ Time Frame: 1 week ]
    Measurement of coronary flow reserve of the left anterior descending coronary artery will be carried out with transthoracic Doppler Echocardiography (TDE) and dipyridamole stress. CFR will be calculated as the ratio between stress and resting flow velocity (cm/sec)

  3. Relationship between coronary flow reserve (CFR) and platelet/plasma BH2 and BH4 levels. [ Time Frame: 1 week ]
    Simple regression analysis or logistic regression will be used to test the relationship between CFR and biopterins values in plasma and platelets.


Secondary Outcome Measures :
  1. Levels of cGMP in platelets [ Time Frame: 1 week ]
    Comparison of levels of cGMP in platelets among normals, patients with normal CFR and patients with reduced CFR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Symptomatic (angina symptoms both typical and atypical ) patients referred to the hospital with hypertension plus risk factors: diabetes, hypercholesterolemia, smoking, chronic renal failure
Criteria

Inclusion Criteria:

  • o men and women (females of childbearing potential must be using highly effective contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner)

    • Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test
    • between 40 and 80 years of age
    • documented history of hypertension
    • smokers/non smokers R
    • type 2 diabetes R
    • Moderate to severe kidney disease (GFR >30 and <60 ml/min/1.73m2 (estimated MDRD) R
    • Hypercholesterolemia R
    • Receiving an optimal standard antihypertensive treatment for at least 6 months, stable for at least 15 days
    • All other concomitant treatments stabilized at least for the preceding 15 days
    • Able to give written informed consent

Exclusion Criteria:

  • o Females of childbearing potential not using highly effective contraceptive precautions

    • Patients with obstructive (>50% diameter reduction) CAD on the LAD (based on invasive angiography or coronary CTA) or with evidence of previous myocardial infarction or history of revascularization in the LAD territory.
    • CAD on the RCA or CX with diameter reduction > 50% (based on invasive angiography or coronary CTA) , either native or revascularized (stent)
    • Patients with infectious disease and/or chronic inflammatory diseases
    • Epicardial coronary arteries spasm
    • Patients with severe valve disease and/or significant left ventricular wall motion abnormalities
    • Patients under treatment with non-selective beta blockers including propranolol, nadolol, pindolol, labetalol, penbutolol, sotalol, carvedilol, and timolol.
    • Contraindications to dipyridamole infusion: asthma, bronchospasm, previous < 24 hours ingestion of phylline derivatives (tea, coffee, cola, xanthines and chocolate) sick sinus syndrome, advanced AV block (second and third degree), systolic blood pressure < 90 mmHg, cerebral ischemia, severe sinus bradycardia (heart rate <40/min), use of dipyridamole during the last 24 h, severe atherosclerotic lesions of extracranial artery >75%.
    • Acute treatment or treatment for acute diseases
    • Patients receiving steroidal anti-inflammatory drugs, dietary supplements of folic acid, or antioxidant vitamins.
    • Any condition that may prevent the pt to give informed consent , enter the study or bias the results.
    • Participating into other studies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03841383


Contacts
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Contact: Ornella P Rimoldi, MD +390226435456 rimoldi.ornella@hsr.it
Contact: Silvia Galvani +390226436206 galvani.silvia@hsr.it

Locations
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Italy
ASST Papa Giovanni XXIII Recruiting
Bergamo, Italy, 24127
Contact: Michele Senni, MD       msenni@asst-pg23.it   
IRCCS Ospedale San Raffaele Recruiting
Milan, Italy, 20132
Contact: Paolo G Camici, Md         
Sponsors and Collaborators
IRCCS San Raffaele
Servier
Investigators
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Principal Investigator: Paolo G Camici, MD IRCCS Ospedale San Raffaele

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Responsible Party: Prof. Paolo G Camici MD FACC, Professor of Cardiology, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT03841383     History of Changes
Other Study ID Numbers: CFRBH4_IT1
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Essential Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Dipyridamole
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents