ObesityPhase 1OCAPUSHNCT02532335
Obeticholic Acid in Morbidly Obese Patients and Healthy Volunteers
A Phase 1 study testing Obeticholic acid in people with Obesity, run by Sahlgrenska University Hospital at 2 sites in Sweden.
Trial summary
OCAPUSH (EudraCT 2014-002313-33) is a double-blind placebo-controlled parallel-arms study of the effects of obeticholic acid on farnesoid X receptor expression in jejunum and on gut microbiota in morbidly obese patients and healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Obeticholic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesSweden
- Study dates
- Aug 2015to Jun 2021
- Phase
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Morbid obesity awaiting gastric bypass surgery, ≥35 kg/m2
- Male subjects, pre-, and post-menopausal female subjects
- Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives
- Patients eligible to laparoscopic bariatric surgery
- Patients must give their signed and dated written consent to participate in this study based on written information of all pertinent aspects of the trial provided at least 24 hours before undertaking any trial related activity.
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.
- Hypothyroidism, unless the subject is clinically euthyroid, receiving a stable dose thyroid hormone replacement therapy and serum TSH is within the normal range.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites, 2 recruiting
- Recruiting
Hanns-Ulrich Marschall
Gothenburg, 411 31
Hanns-Ulrich Marschall, +4670774073, hanns-ulrich.marschall@gu.se
Hanns-Ulrich Marschall, MD, PhD
- Enrolling by invitation
Sahlgrenska Academy
Gothenburg
About this study
Official title: Study of the Effects of Obeticholic Acid on Farnesoid X Receptor Expression in Jejunum and on Gut Microbiota in Morbidly Obese Patients and Healthy Volunteers
OCAPUSH (EudraCT 2014-002313-33) is a double-blind placebo-controlled parallel-arms study of the effects of obeticholic acid on farnesoid X receptor expression in jejunum and on gut microbiota in morbidly obese patients and healthy volunteers. Obeticholic acid (OCA, 6-ethyl-chenodeoxycholic acid, INT-747) is a semi-synthetic derivative of the major human bile acid chenodeoxycholic acid and will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum.These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI >35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejunum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.
Read the detailed description
Obeticholic acid will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum. These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI >35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejenum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.
- Conditions
- Obesity
- Being tested
- Obeticholic acid, Obeticholic acid placebo
- Keywords
- FXR, bile acids, FGF19, C4, gut microbiota, Pharmacodynamics of FXR activation in the small bowel
- Medical subject headings
- Obesity
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
active drug
Obeticholic acid placeboDrug
Also called INT-747 placebo
matching placebo
| 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: Obeticholic acid; Drug: Obeticholic acid placebo |
| Healthy Volunteers OCA | Active comparator | Obeticholic acid Obeticholic acid 25 mg/day in three weeks Receives: Drug: Obeticholic acid |
| Healthy volunteers Placebo | Placebo comparator | Obeticholic acid 25 mg/day matching placebo in three weeks Receives: Drug: Obeticholic acid; Drug: Obeticholic acid placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine
ChIP-assay in biopsies
Measured: Three weeks
Secondary outcomes (1)
Shot-gun metagenomics as a measure of Impact of FXR activation on gut microbiota
Shot-gun metagenomics
Measured: Three weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionDec 2020 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hanns-Ulrich Marschall, Sahlgrenska University Hospital
- Investigators
- Hanns-Ulrich Marschall, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02532335
- Sponsor's protocol ID
- OCAPUSH
- Acronym
- OCAPUSH
- Status last verified
- Aug 2020
- First submitted
- 21 Aug 2015
- Last updated
- 25 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effects of Obeticholic Acid on Farnesoid X Receptor Expression in Jejunum and on Gut Microbiota in Morbidly Obese Patients and Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02532335
- Acronym / sponsor ID
- OCAPUSH / OCAPUSH
- Conditions
- Obesity
- Keywords
- FXR, bile acids, FGF19, C4, gut microbiota, Pharmacodynamics of FXR activation in the small bowel
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 25 Aug 2015 (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.
OCAPUSH (EudraCT 2014-002313-33) is a double-blind placebo-controlled parallel-arms study of the effects of obeticholic acid on farnesoid X receptor expression in jejunum and on gut microbiota in morbidly obese patients and healthy volunteers. Obeticholic acid (OCA, 6-ethyl-chenodeoxycholic acid, INT-747) is a semi-synthetic derivative of the major human bile acid chenodeoxycholic acid and will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum.These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI >35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejunum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.
Detailed description
Obeticholic acid will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum. These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI >35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejenum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- 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: Obeticholic acid, Drug: Obeticholic acid placeboObeticholic acid 25 mg/day matching placebo in three weeks |
| Healthy Volunteers OCA | Active comparator | Drug: Obeticholic acidObeticholic acid Obeticholic acid 25 mg/day in three weeks |
| Healthy volunteers Placebo | Placebo comparator | Drug: Obeticholic acid, Drug: Obeticholic acid placeboObeticholic acid 25 mg/day matching placebo in three weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Morbid obesity awaiting gastric bypass surgery, ≥35 kg/m2
- Male subjects, pre-, and post-menopausal female subjects
- Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives
- Patients eligible to laparoscopic bariatric surgery
- Patients must give their signed and dated written consent to participate in this study based on written information of all pertinent aspects of the trial provided at least 24 hours before undertaking any trial related activity.
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-747active drug | Drug | Healthy Volunteers OCA, Healthy volunteers Placebo, Morbid Obesity OCA, Morbid Obesity Placebo |
| Obeticholic acid placeboAlso: INT-747 placebomatching placebo | Drug | Healthy volunteers Placebo, Morbid Obesity Placebo |
Primary outcome
ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine
Time frame: Three weeks
ChIP-assay in biopsies
1 secondary outcome
Shot-gun metagenomics as a measure of Impact of FXR activation on gut microbiota
Time frame: Three weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
- Individual participant dataSharing planned: No
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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 principal investigator
Sahlgrenska University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Obeticholic acid in people with Obesity, run by Sahlgrenska University Hospital at 2 sites 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 5 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: status not confirmed, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hanns-Ulrich Marschall, MD, PhD, MSc (+46708774073, hanns-ulrich.marschall@gu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine (time frame: Three weeks). 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 25 Aug 2020.