Mendelian Reverse Cholesterol Transport Study

NCT01782027 | Terminated

• 1 other identifier: 815075
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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 people carrying mutations in genes known to affect high density lipoprotein (HDL) metabolism by analyzing changes in the tracer activity in total plasma, lipoproteins fractions and feces.

Conditions

Cholesterol, HDL; Lipid Metabolism, Inborn Errors; Tangier Disease; LCAT Deficiency; Cholesteryl Ester Transfer Protein (CETP) Deficiency

Keywords

healthy controls; Tangier Disease; Adenosine triphosphate-binding cassette transporter 1 (ABCA1); apoA-I; LCAT deficiency; Scavenger receptor BI (SRBI) deficiency; CETP deficiency

Outcome Measures

Primary Outcomes (1)

• determination of 3H cholesterol in plasma and lipoproteins

  up to 192 hr

Secondary Outcomes (1)

• determination of 3H cholesterol and its metabolites in red blood cells over time

  up to 192 hr

Other Outcomes (1)

• determination of 3H cholesterol activity in feces

  up to 192 hours

Study Arms (1)

3H-cholesterol

EXPERIMENTAL

Drug: 3H-cholesterol bound to albumin

Interventions

3H-cholesterol bound to albumin DRUG

up to 100 uCi of \[3H\]-cholesterol (containing approximately 0.2 mg of cholesterol) mixed with a solution containing human serum albumin will be administered as an intravenous bolus injection

Also known as: particulate cholesterol

3H-cholesterol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 18 and 75
• Subjects must be:
• Carriers of functional mutations of genes encoding proteins affecting HDL metabolism;
• Healthy control subjects with HDL cholesterol levels within the normal range of the lab where screening tests are run, or at the discretion of the investigator, and matched for gender, race, age (± 5 years) to the patients.
• Negative screening pregnancy test if female of child bearing potential (females of child-bearing potential must be following a medically accepted form of contraception)
• Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form.
• Subjects must be willing and able to comply with all study-related procedures.

You may not qualify if:

• Known cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease (control subjects only)
• History of diabetes mellitus or fasting glucose \> 126 mg/dL at the screening visit (control subjects only).
• Any current, unstable endocrine disease as assessed by collection of medical history during screening. Subjects with rare Mendelian disorders with thyroid disease that is well controlled by stable treatment may be considered for enrollment at the discretion of the principal investigator
• History of previous malignancy, other than basal cell or squamous cell carcinoma of the skin, from which the patient has been disease free for less than 5 years as assessed by collection of medical history during screening
• Current diagnosis of anemia as assessed by collection of medical history during screening or hemoglobin less than 10 g/dL as evaluated during safety lab at screening
• History of kidney disease or chronic renal insufficiency, as defined as estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2 in control subjects and patients with other disorders of HDL metabolism and eGFR \< 30 ml/min/1.73m2 in subjects with Lecithin-Cholesterol Acyltransferase (LCAT) deficiency.
• Any active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition as assessed by collection of medical history during screening, and judged by the investigator to be a major condition.
• Sustained uncontrolled hypertension (Systolic \>160 mm Hg and/or Diastolic BP \>100 mmHg) at screening. Blood pressure may be re-tested twice after initial assessment in the supine position at five minute intervals (for a total of 3 blood pressure assessments). The pressure elevation is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits for all three assessments
• Use of warfarin, or any known coagulopathy and /or elevated prothrombin time/partial thromboplastin time (PT/PTT) \>1.5 x upper limit of normal (ULN)
• Self-reported history of human immunodeficiency virus (HIV) positive
• History of previous organ transplantation, as assessed by collection of medical history during screening
• Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5x ULN, or self-reported history of positive Hepatitis B or Hepatitis C test result
• Any surgical procedure that occurred within the previous 3 months of the screening visit, as assessed by collection of medical history during screening, and judged by the investigator to be a major procedure.
• History of drug abuse (\< 1 year), as assessed by collection of medical history during screening procedures
• Regular abuse of alcoholic beverages (\> 2 drinks/day), as assessed by collection of medical history during screening procedures

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lipid Metabolism, Inborn Errors; Tangier Disease; Lecithin Cholesterol Acyltransferase Deficiency; Cholesteryl Ester Transfer Protein Deficiency

Condition Hierarchy (Ancestors)

Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Hypoalphalipoproteinemias; Hypolipoproteinemias; Dyslipidemias

Study Officials

• Marina Cuchel, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: October 1, 2012
• Primary Completion: September 4, 2024
• Study Completion: September 4, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (1)