Metabolic SyndromeEarly Phase 1NCT00465751
Effects of FXR Activation on Hepatic Lipid and Glucose Metabolism
A Early Phase 1 study testing chenodeoxycholic acid in people with Metabolic Syndrome and Familial Hypertriglyceridemia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Syndrome, Familial Hypertriglyceridemia, Familial Combined Hyperlipidemia
- What is being tested?
- chenodeoxycholic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Oct 2004to not given
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- chenodeoxycholic acid, placebo capsules
- Medical subject headings
- Metabolic Syndrome, Hyperlipoproteinemia Type IV, Hyperlipidemia, Familial Combined
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chenodeoxycholic acidDrug
chenodeoxycholic acid 500 mg capsules tid po
placebo capsulesDrug
placebo capsules containing mannitol tid po
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | chenodeoxycholic acid treatment Receives: Drug: chenodeoxycholic acid |
| B | Placebo comparator | placebo treatment Receives: Drug: placebo capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma triglyceride concentrations
Measured: 3 months
Secondary outcomes (2)
hepatic insulin sensitivity
Measured: 3 months
heptic triglyceride content
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2007 (estimated)
- Study startOct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefan Bilz, MD, Principal investigator, Cantonal Hospital of St. Gallen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00465751
- Sponsor's protocol ID
- EKBB 211/04 SB
- Status last verified
- Mar 2012
- First submitted
- 24 Apr 2007
- Last updated
- 9 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00465751
- Acronym / sponsor ID
- EKBB 211/04 SB
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Oct 2004
- First posted
- 25 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: chenodeoxycholic acidchenodeoxycholic acid treatment |
| B | Placebo comparator | Drug: placebo capsulesplacebo treatment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Age between 18 and 65 years.
- Patients with a metabolic syndrome defined by the presence of >= 3 of the following criteria:
- Patients with Familial Combined Hyperlipidemia characterized by the following criteria:
- Patients with Familial Hypertriglyceridemia characterized by the following criteria:
- Controls fulfilling the following criteria:
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| chenodeoxycholic acidchenodeoxycholic acid 500 mg capsules tid po | Drug | A |
| placebo capsulesplacebo capsules containing mannitol tid po | Drug | B |
Primary outcome
plasma triglyceride concentrations
Time frame: 3 months
2 secondary outcomes
hepatic insulin sensitivity
Time frame: 3 months
heptic triglyceride content
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Bilz, MD principal investigator
Cantonal Hospital of St. Gallen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing chenodeoxycholic acid in people with Metabolic Syndrome and Familial Hypertriglyceridemia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
plasma triglyceride concentrations (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2012.