ObesityPhase 2OCABSGSNCT01625026
Obeticholic Acid in Bariatric and Gallstone Disease
A Phase 2 study testing Obeticholic acid in people with Obesity and Gallstones, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
By binding to the nuclear receptor FXR, bile acids not only regulate their own turn-over but presumably also pivotal steps in cholesterol, triglyceride and glucose metabolism as shown in laboratory animals. Obeticholic acid (OCA) is a semisynthetic bile acid with very high affinity to FXR. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Obesity, Gallstones
- What is being tested?
- Obeticholic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2013to Apr 2016
- Phase
- Phase 2
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In the obesity group: BMI ≥35 kg/m2
- In the gallstone group: symptomatic, ultrasound verified gallstone disease
Who cannot join
- Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease)
- Previous gastric or small bowel surgery
- Inflammatory bowel disease
- Uncontrolled diabetes mellitus (fasting blood glucose >6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease.
- Pregnancy. A urine pregnancy test will be performed the day before start of medication. Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives.
- Elevations of transaminases (ALAT/ASAT) or alkaline phosphatase or bilirubin above 2xULN (upper limit of normal) the day before start of medication.
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- Other serious disease, including depressive disorders treated by medication
- Patients who will not comply with the protocol.
- A subject who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the TSH is within normal range.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Obeticholic Acid on Hepatic Fatty Acid/Triglyceride Metabolism and Hepatobiliary Detoxification/Elimination in Morbidly Obese and Gallstone Patients
By binding to the nuclear receptor FXR, bile acids not only regulate their own turn-over but presumably also pivotal steps in cholesterol, triglyceride and glucose metabolism as shown in laboratory animals. Obeticholic acid (OCA) is a semisynthetic bile acid with very high affinity to FXR. In a pharmacodynamic study the effects of OCA on bile acid, lipid and glucose turn-over are studied in 20 morbidly obese and 20 gallstones patents, respectively, that are administered OCA at 25 mg/day in three weeks before bariatric (BS) or gallstone (GS) surgery where in addition to blood samples also biopsies are taken from the liver and in the case of BS, omental and subcutaneous adipose tissue and in case of GS, gallbladder bile.
Read the detailed description
In a placebo-controlled double-blind randomized trial, 20 otherwise healthy morbidly obese patients scheduled for bariatric surgery, and 20 otherwise healthy gallstone patients will be administered 25 mg/day INT-747 or placebo for three weeks until the day before surgery. Serum from days 1 and 21 will be analyzed for routine liver tests, bile acids, a complete lipid profile including FA and in addition for 7α-hydroxy-4-cholesten-3-one and FGF-19, markers for bile acid synthesis and its intestinal stimulation. For the evaluation of insulin resistance and possible pre-diabetes, plasma will be taken for the estimation of HOMA index and oral glucose tolerance test (OGTT) will be performed at days 1 and 21. At surgery, a liver biopsy (0.5-1 g) and a white adipose tissue (WAT) specimen (1 cm2) will be taken and immediately frozen in liquid nitrogen for mRNA and protein preparation for quantitative RT-PCR and Western analysis, respectively, histopathological NAFLD grading, and measuring of hepatic and WAT lipase activity. In gallstone patients, gallbladder bile will be sampled for the measurements of biliary lipids (cholesterol, phospholipids, bile acids) and the calculation of the cholesterol saturation index.
- Conditions
- Obesity, Gallstones
- Being tested
- Obeticholic acid, Placebo
- Keywords
- Morbidly obesity, Gastric bypass, Cholecystolithiasis
- Medical subject headings
- Obesity, Gallstones, Cholecystolithiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obeticholic acidDrug
Also called INT-747
Obeticholic acid 25 mg/day in three weeks
PlaceboDrug
Also called Placebo INT-747
Placebo to obeticholic acid
| Study group | Role | What they receive |
|---|---|---|
| Morbid Obesity OCA | Active comparator | Obeticholic acid 25 mg/day in three weeks Receives: Drug: Obeticholic acid |
| Morbid Obesity Placebo | Placebo comparator | Obeticholic acid 25 mg/day matching placebo in three weeks Receives: Drug: Placebo |
| Gallstones OCA | Active comparator | Obeticholic acid 25 mg/day in three weeks Receives: Drug: Obeticholic acid |
| Gallstones Placebo | Placebo comparator | Obeticholic acid 25 mg/day matching placebo in three weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of OCA on FXR-dependent metabolism
Primary endpoints
- relative changes in markers for insulin resistance
- relative changes in FA and TG
- relative changes in hepatic and adipose tissue lipase expression and activity
- relative changes in hepatic apical transport proteins ABCG5/8, BSEP, MDR3, MRP2
- relative changes in hepatic ER stress markers
Measured: Day 21
Secondary outcomes (1)
Effects of OCA on serum lipid levels
Secondary endpoints
- relative changes in m RNA expression levels of genes listed under 3.ix
- relative changes in hepatic basolateral transport proteins listed under 3.x
- relative change in serum bile acids as listed under 3.xii, including INT-747
- relative changes in biliary lipids (cholesterol, phospholipids, bile acids)
- relative change in plasma 7α-hydroxy-4-cholesten-3-one and FGF-19
- relative changes in total cholesterol, LDL-C, HDL-C, Apo A1, Apo B, in Lp(A)
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study startSep 2013
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe 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
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of Vienna
- Responsible party
- Principal investigator, Hanns-Ulrich Marschall, Sahlgrenska University Hospital
- Investigators
- Hanns-Ulrich Marschall, MD, PhD, Principal investigator, Sahlgrenska University Hospital Gothenburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625026
- Sponsor's protocol ID
- OCABSGS
- Acronym
- OCABSGS
- Status last verified
- Oct 2016
- First submitted
- 19 Jun 2012
- Last updated
- 18 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Al-Dury S, Wahlstrom A, Panzitt K, Thorell A, Stahlman M, Trauner M, Fickert P, Backhed F, Fandriks L, Wagner M, Marschall HU. Obeticholic acid may increase the risk of gallstone formation in susceptible patients. J Hepatol. 2019 Nov;71(5):986-991. doi: 10.1016/j.jhep.2019.06.011. Epub 2019 Jun 27.
PubMed 31254596
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Obeticholic Acid on Hepatic Fatty Acid/Triglyceride Metabolism and Hepatobiliary Detoxification/Elimination in Morbidly Obese and Gallstone Patients
- ClinicalTrials.gov ID
- NCT01625026
- Acronym / sponsor ID
- OCABSGS / OCABSGS
- Conditions
- Obesity, Gallstones
- Keywords
- Morbidly obesity, Gastric bypass, Cholecystolithiasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Collaborators
- Medical University of Vienna
- Study start
- Sep 2013
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 21 Jun 2012 (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.
By binding to the nuclear receptor FXR, bile acids not only regulate their own turn-over but presumably also pivotal steps in cholesterol, triglyceride and glucose metabolism as shown in laboratory animals. Obeticholic acid (OCA) is a semisynthetic bile acid with very high affinity to FXR. In a pharmacodynamic study the effects of OCA on bile acid, lipid and glucose turn-over are studied in 20 morbidly obese and 20 gallstones patents, respectively, that are administered OCA at 25 mg/day in three weeks before bariatric (BS) or gallstone (GS) surgery where in addition to blood samples also biopsies are taken from the liver and in the case of BS, omental and subcutaneous adipose tissue and in case of GS, gallbladder bile.
Detailed description
In a placebo-controlled double-blind randomized trial, 20 otherwise healthy morbidly obese patients scheduled for bariatric surgery, and 20 otherwise healthy gallstone patients will be administered 25 mg/day INT-747 or placebo for three weeks until the day before surgery. Serum from days 1 and 21 will be analyzed for routine liver tests, bile acids, a complete lipid profile including FA and in addition for 7α-hydroxy-4-cholesten-3-one and FGF-19, markers for bile acid synthesis and its intestinal stimulation. For the evaluation of insulin resistance and possible pre-diabetes, plasma will be taken for the estimation of HOMA index and oral glucose tolerance test (OGTT) will be performed at days 1 and 21. At surgery, a liver biopsy (0.5-1 g) and a white adipose tissue (WAT) specimen (1 cm2) will be taken and immediately frozen in liquid nitrogen for mRNA and protein preparation for quantitative RT-PCR and Western analysis, respectively, histopathological NAFLD grading, and measuring of hepatic and WAT lipase activity. In gallstone patients, gallbladder bile will be sampled for the measurements of biliary lipids (cholesterol, phospholipids, bile acids) and the calculation of the cholesterol saturation index.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Morbid Obesity OCA | Active comparator | Drug: Obeticholic acidObeticholic acid 25 mg/day in three weeks |
| Morbid Obesity Placebo | Placebo comparator | Drug: PlaceboObeticholic acid 25 mg/day matching placebo in three weeks |
| Gallstones OCA | Active comparator | Drug: Obeticholic acidObeticholic acid 25 mg/day in three weeks |
| Gallstones Placebo | Placebo comparator | Drug: PlaceboObeticholic acid 25 mg/day matching placebo in three weeks |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- In the obesity group: BMI ≥35 kg/m2
- In the gallstone group: symptomatic, ultrasound verified gallstone disease
Key exclusion criteria (9 listed)
- Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease)
- Previous gastric or small bowel surgery
- Inflammatory bowel disease
- Uncontrolled diabetes mellitus (fasting blood glucose >6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease.
- Pregnancy. A urine pregnancy test will be performed the day before start of medication. Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives.
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 |
|---|---|---|
| Obeticholic acidAlso: INT-747Obeticholic acid 25 mg/day in three weeks | Drug | Gallstones OCA, Morbid Obesity OCA |
| PlaceboAlso: Placebo INT-747Placebo to obeticholic acid | Drug | Gallstones Placebo, Morbid Obesity Placebo |
Primary outcome
Effects of OCA on FXR-dependent metabolism
Time frame: Day 21
Primary endpoints * relative changes in markers for insulin resistance * relative changes in FA and TG * relative changes in hepatic and adipose tissue lipase expression and activity * relative changes in hepatic apical transport proteins ABCG5/8, BSEP, MDR3, MRP2 * relative changes in hepatic ER stress markers
1 secondary outcome
Effects of OCA on serum lipid levels
Time frame: 21 days
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 18 Oct 2016.
- Derived from this study: PubMed 31254596Al-Dury S, Wahlstrom A, Panzitt K, Thorell A, Stahlman M, Trauner M, Fickert P, Backhed F, Fandriks L, Wagner M, Marschall HU. Obeticholic acid may increase the risk of gallstone formation in susceptible patients. J Hepatol. 2019 Nov;71(5):986-991. doi: 10.1016/j.jhep.2019.06.011. Epub 2019 Jun 27.
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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.
Hanns-Ulrich Marschall, MD, PhD principal investigator
Sahlgrenska University Hospital Gothenburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Obeticholic acid in people with Obesity and Gallstones, run by Sahlgrenska University Hospital at 1 site in Sweden.
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 2 inclusion and 9 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 18 Oct 2016. 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 Sweden. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Effects of OCA on FXR-dependent metabolism (time frame: Day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01625026, which also lists 1 linked publication.
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 18 Oct 2016.