MeMo: Reverse Cholesterol Transport (RCT) Study

Sponsor

University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT01031758

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Arms

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Other: 3H-Cholesterol	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: Group 1 Group 1 is comprised of 6 healthy subjects with HDL-C levels between the 25th and 75th percentile.	Other: 3H-Cholesterol 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.
Other: Group 2 Group 2 is comprised of 6 healthy subjects with high HDL-C levels > 75th percentile.	Other: 3H-Cholesterol 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.
Other: Group 3 Group 2 is comprised of 6 healthy subjects with low HDL-C levels < 25th percentile.	Other: 3H-Cholesterol 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.

Arm

Intervention/Treatment

Other: Group 1

Group 1 is comprised of 6 healthy subjects with HDL-C levels between the 25th and 75th percentile.

Other: 3H-Cholesterol

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.

Other: Group 2

Group 2 is comprised of 6 healthy subjects with high HDL-C levels > 75th percentile.

Other: 3H-Cholesterol

Other: Group 3

Group 2 is comprised of 6 healthy subjects with low HDL-C levels < 25th percentile.

Other: 3H-Cholesterol

Outcome Measures

Primary Outcome Measures

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

Presence of the tracer in feces. [Time zero to 96 Hour inclusive]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.