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Dried Blood Spot- Statin Pilot Study (DBS)

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ClinicalTrials.gov Identifier: NCT02402803
Recruitment Status : Terminated (No recruitment)
First Posted : March 30, 2015
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Noel Bairey Merz, Cedars-Sinai Medical Center

Brief Summary:

Cardiovascular disease (CVD) is the number one cause of mortality for men and women in the United States. Dyslipidemia, particularly a high low-density-lipoprotein cholesterol (LDL-C) level, is a well-established cardiovascular risk factor and the current American Heart Association guideline for CVD risk assessment recommends a lipid panel to be checked. In addition, guidelines recommend statin therapy in all patients with clinical atherosclerotic CVD, all patients with LDL-C = 190 mg/dL, patients age 40-75 years with diabetes and LDL-C 70-189 mg/dL, and patients with an estimated 10-year atherosclerotic CVD risk = 7.5%. For all of these patients, a fasting lipid panel should be drawn prior to statin initiation as well as during follow-up to assess medication and lifestyle adherence. These fasting lipid panels are obtained via conventional phlebotomy via venopuncture in an office-based or hospital laboratory setting. However, research protein quantitation with mass spectrometry and enzyme-linked immunosorbent assay (ELISA) are technologies that allow for sensitive quantitation of protein biomarkers and targets, including lipoproteins. Most importantly, multiple reaction monitoring (MRM) mass spectrometry is able to assess samples from a dried blood spot (DBS), whose advantages include minimal volume requirements, ease of sample attainment by finger stick with minimal training required, ease of transport, and sample stability.

The purpose of the proposed analysis is to 1) measure changes in CVD biomarkers before and after initiation of statin therapy and 2) compare lipid measurements by conventional phlebotomy blood samples to research protein quantitation measurements in DBS and plasma.


Condition or disease Intervention/treatment
Hyperlipidemias Cardiovascular Diseases Other: Dried blood spot testing and phlebotomy

Detailed Description:

Despite reductions in cardiovascular disease (CVD) mortality in the past 20 years, CVD remains the leading cause of mortality in the United States, accounting for ~1 of every 3 deaths. CVD costs the U.S. over $100 billion annually and is an important field for targeted primary and secondary prevention. Dyslipidemia, particularly a high low-density-lipoprotein cholesterol (LDL-C) level, is a well-established cardiovascular risk factor, and fasting lipid panels (including total cholesterol, LDL-C, triglycerides, and high-density-lipoprotein cholesterol [HDL-C]) are included in the recent 2013 ACC/AHA Risk Assessment Guidelines. Clinical trials have shown that low density lipoprotein cholesterol (LDL-C) reduction with statin therapy predicts cardiovascular event reduction. About a quarter of all adults >45 years old were on statin therapy in 2008, and this will likely increase due to the recent 2013 ACC/AHA Cholesterol Management guidelines. These guidelines recommend statin therapy in all patients with clinical atherosclerotic CVD, all patients with LDL-C = 190 mg/dL, patients age 40-75 years with diabetes and LDL-C 70-189 mg/dL, and patients with an estimated 10-year atherosclerotic CVD risk = 7.5%. For all of these patients, a fasting lipid panel should be drawn prior to statin initiation as well as during follow-up to assess medication and lifestyle adherence. These fasting lipid panels are obtained via conventional phlebotomy via venopuncture in an office-based or hospital laboratory setting.

Research protein quantitation with mass spectrometry and enzyme-linked immunosorbent assay (ELISA) are technologies that allow for sensitive quantitation of protein biomarkers and targets, including lipoproteins. Most importantly, multiple reaction monitoring (MRM) mass spectrometry is able to assess samples from a dried blood spot (DBS), whose advantages include minimal volume requirements, ease of sample attainment by finger stick with minimal training required, ease of transport, and sample stability. DBS sampling has been used for clinical and pre-clinical studies, simplifying sample collection and handling. However, research protein quantitation with mass spectrometry and ELISA has not been compared against conventional blood sample for evaluating changes in cholesterol levels during statin therapy.

While LDL-C is well-established in predicting CVD event reduction, other laboratory lipid, thrombotic and inflammatory biomarkers have been shown to be associated with atherosclerotic plaque development or CVD risk. These include Apo A-I, Apo B, Apo E, IgM, plasminogen, TIMP-1, Von Willebrand factor, antithrombin III, cystatin C, mesothelin, C-reactive protein, SAA, LPS-binding protein, mannose-binding lectin, myeloperoxidase, fibrinogen, alpha-1-acid glycoprotein, soluble transferrin receptor, haptoglobin. All of these CVD protein biomarkers can be measured by research protein quantitation techniques.

In a pilot study of 20 subjects, we aim to:

  1. measure changes in a panel of CVD protein biomarkers before and after initiation of statin therapy.
  2. compare clinical laboratory measurements of LDL-C and HDL-C in conventional phlebotomy blood samples with research protein quantitation mass spectrometry and ELISA measurements of LDL-C (Apo B) and HDL-C (Apo A-I) proteins in DBS and plasma.

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Study Type : Observational
Actual Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Dried Blood Spot- Statin Pilot Study
Study Start Date : October 2015
Actual Primary Completion Date : October 2020
Actual Study Completion Date : October 2020

Resource links provided by the National Library of Medicine



Intervention Details:
  • Other: Dried blood spot testing and phlebotomy
    At baseline and 4-6 week follow-up, a phlebotomy serum sample (5 ml) will be collected in one golden-top tube for clinical laboratory measurement of cholesterol (total cholesterol, LDL-C, triglycerides, HDL-C) . During the same phlebotomy, a fingerprick dried blood spot (DBS) sample and two lavender EDTA plasma tubes (5 ml each) will be collected for analysis of CVD protein markers


Primary Outcome Measures :
  1. Clinical lipid and research protein measurements (composite) [ Time Frame: up to 4-6 week follow-up ]
    Compare LDL-C and HDL-C clinical laboratory test measurements in serum vs Apo B and ApoA-I research protein measurements in DBS and plasma as to correlation coefficient across subject samples and level of response (expected reduction) in LDL/Apo B following initiation of statin therapy


Secondary Outcome Measures :
  1. Biomarker change [ Time Frame: Baseline and 4-6 week follow-up ]
    Compare biomarker changes Pre- vs Post-statin treatment as observed by LDL-C and HDL-C clinical laboratory tests, research protein measurements in plasma and in dried blood spot

  2. Research protein measurements in dried blood spot vs plasma [ Time Frame: Baseline and 4-6 week follow-up ]
    3) Compare research protein measurements of CVD protein markers in dried blood spot and plasma samples to investigate parallelism of results

  3. Clinical Cardiovascular Risk Score [ Time Frame: Baseline ]
    Compare the research protein measurements of CVD protein markers with the ACC/AHA 10-year atherosclerotic CVD risk score


Biospecimen Retention:   Samples Without DNA
cholesterol panel (total cholesterol, LDL-C, triglycerides, HDL-C), Apo A-I, Apo B, Apo E, IgM, plasminogen, TIMP-1, Von Willebrand factor, antithrombin III, cystatin C, mesothelin, C-reactive protein, SAA, LPS-binding protein, mannose-binding lectin, myeloperoxidase, fibrinogen, alpha-1-acid glycoprotein, soluble transferrin receptor, haptoglobin.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Men and women age> 18 years who are initiated on statin therapy in the clinical setting
Criteria

Inclusion criteria:

1. Men and women age> 18 years who are initiated on statin therapy in the clinical setting.

Exclusion criteria:

  1. History of rhabdomyolysis
  2. History of prior allergic reaction to statins
  3. History of liver failure
  4. Contraindications to antecubital phlebotomy or finger stick (including those with bilateral dialysis AV fistulae).

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): NCT02402803


Locations
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United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
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Principal Investigator: C. Noel Bairey Merz, MD Cedars-Sinai Medical Center
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Responsible Party: Noel Bairey Merz, Principal Investigator, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT02402803    
Other Study ID Numbers: Pro00037026
First Posted: March 30, 2015    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Additional relevant MeSH terms:
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Cardiovascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases