Los Angeles, California 90048


Purpose:

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.


Study summary:

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.


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).


Study is Available At:


Original ID:

Pro00037026


NCT ID:

NCT02402803


Secondary ID:


Study Acronym:

DBS


Brief Title:

Dried Blood Spot- Statin Pilot Study


Official Title:

Dried Blood Spot- Statin Pilot Study


Overall Status:

Recruiting


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Cedars-Sinai Medical Center


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Observational


Study Design:


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

20


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:C. Noel Bairey Merz, MD
Principal Investigator
Cedars-Sinai Medical Center
Primary Contact:Ying Mou, PhD
310-248-7669
ying.mou@cshs.org
Backup Contact:Sophie Yoo, MS
424-315-4306
Jihye.Yoo@cshs.org

Study Dates

Start Date:October 2015
Completion Date:October 2019
Completion Type:Anticipated
Primary Completion Date:October 2019
Primary Completion Type:Anticipated
Verification Date:April 2019
Last Changed Date:April 22, 2019
First Received Date:March 25, 2015

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Clinical Cardiovascular Risk Score
Time Frame:Baseline
Safety Issues:False
Description:Compare the research protein measurements of CVD protein markers with the ACC/AHA 10-year atherosclerotic CVD risk score
Outcome Type:Secondary Outcome
Measure:Research protein measurements in dried blood spot vs plasma
Time Frame:Baseline and 4-6 week follow-up
Safety Issues:False
Description:3) Compare research protein measurements of CVD protein markers in dried blood spot and plasma samples to investigate parallelism of results
Outcome Type:Secondary Outcome
Measure:Biomarker change
Time Frame:Baseline and 4-6 week follow-up
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Clinical lipid and research protein measurements (composite)
Time Frame:up to 4-6 week follow-up
Safety Issues:False
Description: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 followi

Study Interventions

Intervention Type:Other
Name:Dried blood spot testing and phlebotomy
Description: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

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Cedars-Sinai Medical Center

Samples and Retentions

Sample Retention:Samples Without DNA
Description: 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.
Study Population: Men and women age> 18 years who are initiated on statin therapy in the clinical setting
Sample Method:Non-Probability Sample

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


If you would like to be contacted by the clinical trial representative please fill out the form below.