Metabolic Syndrome, Familial Hypertriglyceridemia, Familial Combined Hyperlipidemia
Conditions
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.
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.
Interventions
chenodeoxycholic acid 500 mg capsules tid po
DRUGplacebo capsules
placebo capsules containing mannitol tid po
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| plasma triglyceride concentrations | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| hepatic insulin sensitivity | 3 months |
| heptic triglyceride content | 3 months |
Countries
Switzerland
Outcome results
None listed