The Association of SAA With Apolipoprotein B Affects Cardiovascular Risk

NCT02770872 | Completed

• 1 other identifier: TAN-14-002-HAF
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular disease (CVD) is the leading cause of death in developed nations and a major health issue in Veterans. Despite a number of different treatments, cardiovascular disease remains a major health burden, thus further treatments are needed. Individuals with obesity and/or diabetes are at particularly high risk for cardiovascular disease, and research suggests that elevated levels of serum amyloid A (SAA) may contribute to cardiovascular disease, particularly atherosclerosis. In preliminary studies in both mouse and human the investigators have identified that SAA appears to shift between lipid particles. SAA is mainly found on high density lipoprotein (HDL) particles; however, the investigators have found that in both mice and humans with obesity and/or diabetes SAA is found on low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles, and the investigators hypothesize that the presence of SAA on LDL or VLDL makes these particles more likely to cause cardiovascular disease. To determine what leads SAA to shift between lipid particles, SAA knockout mice will be injected with HDL containing SAA then blood collected at several time points over 24 hours, and the lipid particles will be isolated to measure SAA. In some experiments the investigators will compare different isoforms of SAA, different types of HDL particles, or induce expression of enzymes likely involved in shifting SAA between particles. To determine if the presence of SAA makes lipid particles bind vascular matrix more strongly, the investigators will collect carotid arteries and compare the extent of lipid particles bound to the vascular matrix in the vessel wall when the particles have or do not have SAA present. If this research confirms this hypothesis then the presence of SAA on LDL or VLDL may 1) be a new marker indicating humans at highest risk for cardiovascular disease and 2) be a new target of therapy to prevent cardiovascular disease.

Conditions

Cardiovascular Disease

Keywords

serum amyloid a; lipoprotein; insulin resistance; dyslipidemia

Outcome Measures

Primary Outcomes (2)

• Post-prandial SAA content on apoB containing lipoproteins after consumption of a high fat shake

  Subjects will arrive at the clinic fasted and have an IV line established. A baseline blood sample will be drawn at hour zero. The subject will then consume a high fat shake within a 15 minute window. Blood samples will then be drawn every hour for eight hours to determine the time course of SAA shifting from HDL to apoB containing lipoproteins.

  Baseline and once every hour for 8 hours. Study completed in a single day

• Degree of insulin resistance

  Subjects will arrive at the clinic fasted. The subject will have IV sites established in both arms and two baseline blood samples will be drawn (-30 and -10 minute). At time zero, a bolus of glucose will be injected followed by blood sample collection. Blood will be collected at the following time points in minutes; 0, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19. At time 20 minutes, the subject will receive an IV bolus of insulin and frequent blood sampling will continue at the following time points in minutes; 20, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140 ,160, 180, 210, 240. A total of 32 blood samples will be collected over the course of 4.5 hours.

  4.5 hour study completed in a single day

Study Arms (3)

Obese, normal

Approximately 25 subjects aged 50-75 with BMI's between 27-45 kg/m2. Observation of SAA on apoB containing lipoproteins

Other: Observation of SAA on apoB containing lipoproteins

Obese, MetS

Approximately 25 subjects aged 50-75 with BMI's between 27-45 kg/m2, blood pressure above 135/80, HDL less than 40 mg/dl, triglycerides greater the 150 mg/dl and fasting blood glucose greater than 100 mg/dl but less than 126 mg/dl. Observation of SAA on apoB containing lipoproteins

Other: Observation of SAA on apoB containing lipoproteins

Obese, diabetic

Approximately 25 subjects aged 50-75 with BMI's between 27-45 kg/m2 and physician diagnosed diabetes mellitis. Observation of SAA on apoB containing lipoproteins

Other: Observation of SAA on apoB containing lipoproteins

Interventions

Observation of SAA on apoB containing lipoproteins OTHER

attempting to elicit the conditions by which SAA shifts from apo-A1 containing lipoproteins to apoB containing lipoproteins

Obese, MetS; Obese, diabetic; Obese, normal

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will recruit male and female subjects eligible for medical care within the VA healthcare system

You may qualify if:

• Up to 80 U.S. veterans age 50-75 will be recruited in the following three groups:
• Obese (BMI 27-45 kg/m2), metabolically healthy, (25-30 subjects)
• Obese (BMI 27-45 kg/m2), metabolic syndrome, (25-30 subjects)
• Obese (BMI 27-45 kg/m2), diabetic, (25-30 subjects)

You may not qualify if:

• The use of:
• Statins (we will not exclude subjects on lipid lowering medications if they are willing to discontinue them for 1-2 weeks prior to participation)
• Fibrates
• Niacin
• Anti-inflammatory drugs including Thiazolidinediones, non-steroidal anti-inflammatories (NSAID), aspirin, steroids
• Estrogen replacement
• Conditions such as:
• Acute illness
• Chronic inflammatory illness (such as psoriasis, rheumatoid arthritis, lupus, etc.)
• Infections
• Impaired renal function (eGFR \< 60 ml/min)
• Hypo- or hyperthyroidism (subjects biochemically euthyroid on levothyroxine therapy are permitted)
• Gastrointestinal dysfunction
• Lifestyles including:
• Use of tobacco products

Sponsors & Collaborators

• Lisa Tannock: lead
• VA Office of Research and Development: collaborator

Study Sites (1)

VA Medical Center

Lexington, Kentucky, 40515, United States

Location

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Biospecimen

Retention: SAMPLES WITH DNA

Whole blood will be collected, which will contain DNA

MeSH Terms

Conditions

Cardiovascular Diseases; Insulin Resistance; Dyslipidemias

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Lisa R Tannock, MD

  VA Medical System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor/PI

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 12, 2016
• Study Start: February 1, 2014
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2018
• Last Updated: March 29, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)