ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of FXR Activation on Hepatic Lipid and Glucose Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00465751
Recruitment Status : Completed
First Posted : April 25, 2007
Last Update Posted : March 9, 2012
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
The purpose of this study is to determine whether chenodeoxycholic acid decreases de novo hepatic lipogenesis, hepatic fat content, hepatic triglyceride production and plasma triglyceride concentrations and improves hepatic glucose metabolism in patients with the metabolic syndrome, Familial Hypertriglyceridemia and Familial Combined Hyperlipidemia.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Familial Hypertriglyceridemia Familial Combined Hyperlipidemia Drug: chenodeoxycholic acid Drug: placebo capsules Early Phase 1

Detailed Description:

Insulin resistance has been found to be the key pathophysiological factor of the metabolic syndrome and may precede the onset of impaired glucose tolerance, diabetes and dyslipidemia. Recently, nonalcoholic fatty liver disease (NAFLD), has been identified as another feature of this syndrome. Importantly, a close relation between liver fat content and hepatic insulin sensitivity has been described. We hypothesize that activation of FXR with chenodeoxycholic acid decreases hepatic de novo lipogenesis and subsequently hepatic fat content and triglyceride production. The decrease in liver fat content will be associated with improved hepatic insulin sensitivity and a decrease in hepatic glucose production.

Patients diagnosed with metabolic syndrome, familial hypertriglyceridemia or familial combined hyperlipidemia will be recruited from the the outpatients department of the Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Basel. Eligible patients will be admitted to the CRC for metabolic studies, including baseline blood samples for the measurement of hormones, cytokines and adipokines, euglycemic-hyperinsulinemic clamp studies for the assessment of glucose turnover and insulin sensitivity and in vivo NMR studies to determine intrahepatic and intramyocellular lipid content. Patients will alternatively receive chenodeoxycholic acid and placebo. The study population will be compared to a group of age, gender and weight matched normolipidemic controls.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Activation of the Farnesoid X Receptor (FXR) on Hepatic Lipid and Glucose Metabolism in Patients With the Metabolic Syndrome and Familial Forms of Hypertriglyceridemia
Study Start Date : October 2004


Arm Intervention/treatment
Active Comparator: A
chenodeoxycholic acid treatment
Drug: chenodeoxycholic acid
chenodeoxycholic acid 500 mg capsules tid po
Placebo Comparator: B
placebo treatment
Drug: placebo capsules
placebo capsules containing mannitol tid po



Primary Outcome Measures :
  1. plasma triglyceride concentrations [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. hepatic insulin sensitivity [ Time Frame: 3 months ]
  2. heptic triglyceride content [ Time Frame: 3 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age between 18 and 65 years.
  2. Patients with a metabolic syndrome defined by the presence of >= 3 of the following criteria:

    • Abdominal obesity (waist circumference > 102 cm in men, > 88 cm in women)
    • Fasting plasma triglycerides > 1.7 mmol/l
    • HDL cholesterol < 1.0 mmol/l in men and < 1.3 mmol/l in women
    • Blood pressure > 130/85 mmHg or antihypertensive medication
    • Fasting plasma glucose > 6.1 mmol/l
  3. Patients with Familial Combined Hyperlipidemia characterized by the following criteria:

    • Fasting plasma triglycerides > 1.7 mmol/l
    • Fasting plasma apolipoprotein B concentrations > 1.2 g/l
    • Family history with hypertriglyceridemia and/or hypercholesterolemia present in at least 1 additional first degree family members
  4. Patients with Familial Hypertriglyceridemia characterized by the following criteria:

    • Fasting plasma triglycerides > 2.3 mmol/l
    • Family history of hypertriglyceridemia in at least 1 additional first degree family member
    • Absence of the metabolic syndrome as defined above
  5. Controls fulfilling the following criteria:

    • Non smoking.
    • No current or previous organ or systemic disease (including diabetes and lipid disorders).
    • Plasma triglycerides and cholesterol within the normal range (see exclusion criteria).
    • Plasma glucose concentrations <6.1 mmol/l Subjects meeting criterium 1 and any of the criteria 2. - 5. are eligible for the study.

Exclusion Criteria:

  1. Any significant hepatic, cardiac, pulmonary, renal, neurological, musculoskeletal, hematological or endocrine disease.
  2. Any form of primary or secondary hyperlipidemia other than the metabolic syndrome, FHTG or FCHL. [These may include: Familial hypercholesterolemia and Familial defective apolipoprotein B (to be assessed by family history and lipid profiles), and Familial Dysbetalipoproteinemia (to be assessed by apo E genotyping), hypothyroidism, nephrotic syndrome, diabetes mellitus, cholestatic liver disease, drug induced hyperlipidemia (thiazides > 25 mg/d, non cardioselective betablockers, isotretinoin, systemic glucocorticoids, cyclosporin A, tacrolimus, non nucleoside HIV protease inhibitors)].
  3. Plasma TG levels > 12 mmol/l in the past or at any time point during the study.
  4. History of acute pancreatitis
  5. History of cardiovascular disease, i.e. coronary artery disease, cerebrovascular disease, peripheral vascular disease, when assessed by medical history, physical exam. Additionally, a stress test will be performed in subjects with MS and FCHL at risk for CHD (see below).
  6. Pregnant or Breast Feeding women
  7. Woman of childbearing potential not using a reliable method of birth control such as oral contraceptives or IUD.
  8. Alcohol intake of greater than 1 drink daily.
  9. Cigarette smokers
  10. History of claustrophobia
  11. Ferromagnetic implants including pacemakers.
  12. Subjects refusing or unable to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00465751


Locations
Switzerland
University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Stefan Bilz, MD Cantonal Hospital of St. Gallen

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00465751     History of Changes
Other Study ID Numbers: EKBB 211/04 SB
First Posted: April 25, 2007    Key Record Dates
Last Update Posted: March 9, 2012
Last Verified: March 2012

Additional relevant MeSH terms:
Syndrome
Metabolic Syndrome X
Hyperlipidemias
Hyperlipoproteinemias
Hypertriglyceridemia
Hyperlipidemia, Familial Combined
Hyperlipoproteinemia Type IV
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Dyslipidemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Chenodeoxycholic Acid
Cathartics
Gastrointestinal Agents