Reverse Cholesterol Transport (RCT) Study

Study Overview
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Brief Summary
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The purpose of this study is to investigate the use of radiolabeled particulate cholesterol administered intravenously in association with albumin, as a method to study reverse cholesterol transport (RCT) in humans by analyzing changes in the tracer activity in total plasma, lipoproteins and feces.

Detailed Description
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The study will use 3H-cholesterol bound to albumin (particulate cholesterol) to assess the ability of HDL to transport cholesterol to the liver to be eliminated. This process is called Reverse Cholesterol transport and is one of the main mechanisms by which HDL protect against atherosclerotic cardiovascular disease. The availability of a method to assess RCT is important for the development of new drugs which affect RCT and may result in useful treatments for atherosclerosis. This study will evaluate the use of radiolabeled particulate cholesterol administered intravenously in association with albumin, as a method to study reverse cholesterol transport (RCT) in humans by analyzing changes in the tracer activity in total plasma and lipoproteins. The study population is healthy volunteers.

Official Title
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A Pilot Study To Evaluate The Use Of 3H Particulate Cholesterol As A Method To Study Reverse Cholesterol Transport In Humans Followed By A Study On The Effect Of HDL-C On RCT Measured By This Method

Conditions
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Healthy

Intervention / Treatment
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* Other: 3H-Cholesterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1 (6 subjects): Men and women between the ages of 18 and 70 HDL cholesterol (HDL-C) as defined by levels ≥ 25th percentile and ≤ 75th percentile for age, gender and race Female subjects must be of non-childbearing potential. They must have been surgically sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion. Subjects must be in good overall health Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form. Subjects must be willing to comply with all study-related procedures. Group 2 (6 subjects): Men and women between the ages of 18 and 70 HDL cholesterol (HDL-C) as defined by levels <25th percentile for age, gender and race Female subjects must be of non-childbearing potential. They must have been surgically sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion. Subjects must be in good overall health Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form. Subjects must be willing to comply with all study-related procedures. Group 3 (6 subjects): Men and women between the ages of 18 and 70 HDL cholesterol (HDL-C) as defined by levels > 75th percentile for age, gender and race Female subjects must be of non-childbearing potential. They must have been surgically sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion. Subjects must be in good overall health Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form. Subjects must be willing to comply with all study-related procedures. Exclusion Criteria: Known cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit. History of any other endocrine disease History of a non-skin malignancy within the previous 5 years Anemia; Hemoglobin less than 10 g/dL Renal insufficiency as defined by creatinine ³ 1.3 mg/dl Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition History of hypertension Use of warfarin, or any known coagulopathy and /or elevated PT/PTT >1.5 x ULN Self-reported history of HIV positive Previous organ transplantation Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as ALT or AST > 1x ULN, or self-reported history of positive Hepatitis B or Hepatitis C test result Any major surgical procedure that occurred within the previous 3 months of the screening visit Use of tobacco products currently or during the previous 30 days History of drug abuse (< 3 years) Regular use of alcoholic beverages (> 2 drinks/day) Body mass index (BMI) > 30 kg/m2 or < 18.5 kg/m2 Participation in an investigational drug study within 6 weeks prior to the screening visit Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study will be excluded. Use of lipid lowering drugs within the 6 weeks prior to dosing or during the study Use of other prescription or non-prescription drugs (including vitamins and herbal supplements, but excluding replacement hormone therapy) within 2 weeks prior to dosing or during the study, however, acetaminophen up to 2g/day is acceptable. Male subjects who plan to conceive a child within 3 months of the conclusion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>Group 1 is comprised of 6 healthy subjects with HDL-C levels between the 25th and 75th percentile. | Other: 3H-Cholesterol<br>* A single dose of 25-50 μCi 3H free cholesterol -albumin complexes (containing approximately 0.1 - 0.3 mg of cholesterol) will be administered intravenously as a slow bolus injection within 1-2 minutes.<br>|
| Other: Group 2<br>Group 2 is comprised of 6 healthy subjects with high HDL-C levels > 75th percentile. | Other: 3H-Cholesterol<br>* A single dose of 25-50 μCi 3H free cholesterol -albumin complexes (containing approximately 0.1 - 0.3 mg of cholesterol) will be administered intravenously as a slow bolus injection within 1-2 minutes.<br>|
| Other: Group 3<br>Group 2 is comprised of 6 healthy subjects with low HDL-C levels < 25th percentile. | Other: 3H-Cholesterol<br>* A single dose of 25-50 μCi 3H free cholesterol -albumin complexes (containing approximately 0.1 - 0.3 mg of cholesterol) will be administered intravenously as a slow bolus injection within 1-2 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the tracer activity in total plasma and lipoproteins. |  | 10 minutes, Zero hour, 5, 10, 15, 30, 45 minutes, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 18, 24, 48, 72, 96 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of the tracer in feces. |  | Time zero to 96 Hour inclusive | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low HDL, High HDL, HDL, Reverse Cholesterol Transport, RCT, healthy volunteer, 3H, Average HDL