Effects of FXR Activation on Hepatic Lipid and Glucose Metabolism

NCT00465751 | Completed Early Phase 1 DMC

• 1 other identifier: EKBB 211/04 SB
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome; Familial Hypertriglyceridemia; Familial Combined Hyperlipidemia

Outcome Measures

Primary Outcomes (1)

• plasma triglyceride concentrations

  3 months

Secondary Outcomes (2)

• hepatic insulin sensitivity

  3 months

• heptic triglyceride content

  3 months

Study Arms (2)

A

ACTIVE COMPARATOR

chenodeoxycholic acid treatment

Drug: chenodeoxycholic acid

B

PLACEBO COMPARATOR

placebo treatment

Drug: placebo capsules

Interventions

chenodeoxycholic acid DRUG

chenodeoxycholic acid 500 mg capsules tid po

A

placebo capsules DRUG

placebo capsules containing mannitol tid po

B

Eligibility Criteria

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

You may qualify if:

• Age between 18 and 65 years.
• 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
• 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
• 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

You may not qualify if:

• Plasma glucose concentrations \<6.1 mmol/l Subjects meeting criterium 1 and any of the criteria 2. - 5. are eligible for the study.
• Any significant hepatic, cardiac, pulmonary, renal, neurological, musculoskeletal, hematological or endocrine disease.
• Any form of primary or secondary hyperlipidemia other than the metabolic syndrome, FHTG or FCHL. \[These may include: Familial hypercholesterolemia and Familial defective apolipoprotein B (to be assessed by family history and lipid profiles), and Familial Dysbetalipoproteinemia (to be assessed by apo E genotyping), hypothyroidism, nephrotic syndrome, diabetes mellitus, cholestatic liver disease, drug induced hyperlipidemia (thiazides \> 25 mg/d, non cardioselective betablockers, isotretinoin, systemic glucocorticoids, cyclosporin A, tacrolimus, non nucleoside HIV protease inhibitors)\].
• Plasma TG levels \> 12 mmol/l in the past or at any time point during the study.
• History of acute pancreatitis
• 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).
• Pregnant or Breast Feeding women
• Woman of childbearing potential not using a reliable method of birth control such as oral contraceptives or IUD.
• Alcohol intake of greater than 1 drink daily.
• Cigarette smokers
• History of claustrophobia
• Ferromagnetic implants including pacemakers.
• Subjects refusing or unable to give written informed consent.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Metabolic Syndrome; Hyperlipoproteinemia Type IV; Hyperlipidemia, Familial Combined

Interventions

Chenodeoxycholic Acid

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Hypertriglyceridemia

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Stefan Bilz, MD

  Cantonal Hospital of St. Gallen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2007
• First Posted: April 25, 2007
• Study Start: October 1, 2004
• Last Updated: March 9, 2012

Record last verified: 2012-03

Locations

CH (1)