Physiological Study of Human Cholesterol Metabolism and Excretion

NCT01603758 | Completed Phase 1

• 2 other identifiers: 201110042R01HL108160
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The underlying hypothesis is that whole body cholesterol - including cholesterol present in tissues that cannot be measured by standard blood tests - is related to heart disease risk. Endogenous cholesterol will be labeled with an intravenous infusion of one type of cholesterol tracer and dietary cholesterol will be labeled with another. These tracers will be used to measure how fast cholesterol is synthesized and excreted using mass spectrometry to distinguish the tracers. Data will be related to circulating biomarkers (blood tests) and to the thickness of the lining of the carotid artery. The effect of the drug ezetimibe on these processes will also be determined. Successful completion of this study will give us more knowledge about cholesterol metabolism that may be useful in designing new drugs and treatments for patients with heart disease, especially those that are already receiving maximum amounts of current medications.

Conditions

Coronary Heart Disease; Cardiovascular Disease; Dyslipidemia; Disorder of Cholesterol Metabolism

Keywords

Cholesterol; Spectrometry, mass; Deuterium; Kinetics; Cholesterol absorption; Coronary Heart Disease

Outcome Measures

Primary Outcomes (1)

• Fractional Excretion of Endogenous Cholesterol

  The fractional rate of endogenous cholesterol excretion will be measured and related to circulating biomarkers and carotid intima-media thickness (Aim #2) or the change in fractional endogenous cholesterol excretion after treatment with ezetimibe will be determined (Aim #3)

  4 years

Study Arms (2)

Observational Arm

NO INTERVENTION

Cholesterol metabolic parameters will be measured in 100 subjects in an observational study. Results will be related to circulating biomarkers and carotid intima-media thickness.

Ezetimibe Interventional Arm

PLACEBO COMPARATOR

Cholesterol metabolic parameters will be measured before and after ezetimibe or placebo intervention. Changes due to ezetimibe will be determined

Drug: Ezetimibe

Interventions

Ezetimibe DRUG

Ezetimibe 10 mg/day or placebo will be given for 6 weeks

Also known as: Zetia

Ezetimibe Interventional Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aim II. 100 subjects aged 30-80 with stable medical and/or surgical illnesses.
• Aim III. 30 subjects age 18-80 with LDL cholesterol \<190, fasting triglycerides\<250 and stable medical or surgical illnesses.

You may not qualify if:

• Aim II. Subjects taking ezetimibe, bile acid sequestrants or with gastrointestinal or liver disease will be excluded since these may affect whole body cholesterol metabolism.
• Subjects with coronary heart disease or other medical illnesses will not be excluded if medically stable.
• Adults under age 30 and children will be excluded because in our current database there is no relation between carotid intima-media thickness and cardiovascular risk factors in this younger group.
• Aim III. Individuals have risk factors for coronary heart disease that mandate drug treatment according to the National Cholesterol Education Program guidelines will be excluded.

Sponsors & Collaborators

• Richard E. Ostlund Jr., MD: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Lin X, Racette SB, Ma L, Wallendorf M, Davila-Roman VG, Ostlund RE Jr. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol. 2017 Dec;37(12):2364-2369. doi: 10.1161/ATVBAHA.117.310081. Epub 2017 Oct 5.

  PMID: 28982667 DERIVED

• Lin X, Racette SB, Ma L, Wallendorf M, Ostlund RE Jr. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans. Arterioscler Thromb Vasc Biol. 2017 May;37(5):990-996. doi: 10.1161/ATVBAHA.117.309119. Epub 2017 Mar 9.

  PMID: 28279967 DERIVED

MeSH Terms

Conditions

Coronary Disease; Cardiovascular Diseases; Dyslipidemias; Arachnodactyly

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard E Ostlund, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 18, 2012
• First Posted: May 23, 2012
• Study Start: January 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: May 6, 2016

Record last verified: 2016-05

Locations

US (1)