Type 2 Diabetes MellitusPhase 2NCT02033876
Ursodiol on Insulin Sensitivity, Gastric Emptying and Body Weight With Type 2 Diabetes on Metformin
A Phase 2 study testing Ursodiol in people with Type 2 Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
Trial summary
This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Ursodiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Overweight or Obese subjects with BMI> 25 Kg/m2 with Type 2 Diabetes mellitus on Metformin, receiving standard of care for Type 2 DM. Otherwise individuals who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than T2DM) and unstable psychiatric disease.
Men or women. Women of childbearing potential will have a negative pregnancy test before initiation of medication.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Effect of Delayed-Release Ursodeoxycholic Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes on Metformin Treatment
This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. These observations will provide the preliminary data for proposing future therapeutic as well as further mechanistic studies of the role of bile acids in the control of glycemia in T2DM.
Read the detailed description
Background: Intra-jejunal administration of bile acids improves insulin sensitivity.
Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release formulation, stimulates bile acid membrane receptor (TGR-5) and farnesol X (FXR) receptors in the ileum and colon, increasing the secretion of Fibroblast growth factor 19 (FGF-19), GLP-1, oxyntomodulin (OXM), and Peptide (PYY3-36), improving insulin sensitivity and inducing weight loss.
Aim: To study the effect of an ileocolonic formulation of UDCA on insulin sensitivity, postprandial plasma glycemia and incretin levels, gastric emptying and body weight in overweight or obese type 2 diabetic subjects on monotherapy with metformin.
Study design: This is a single center, placebo-controlled, parallel group, single dose randomized controlled trial to study the effect of delayed (ileocolonic)-release UDCA 600 mg twice daily on insulin sensitivity, gastric emptying of liquids and solids (measured by scintigraphy)and weight loss in overweight or obese type 2 diabetic subjects. Participants will be receiving monotherapy with metformin. Blood samples will be collected at defined times to measure glycemia and the incretin (GLP-1, OXM, PYY3-36) fasting levels and responses to the meal.
Anticipated Results: In comparison with placebo, UDCA will increase insulin sensitivity, enhance glycemic control, increase postprandial incretins, and delay gastric emptying (GE) of liquids.
Significance: This study will prove that ileocolonic-release UDCA enhances glycemic control in T2DM patients.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Ursodiol
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UrsodiolDrug
Also called Ursodeoxycholic acid
| Study group | Role | What they receive |
|---|---|---|
| Ursodiol | Experimental | Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily Receives: Drug: Ursodiol |
| Placebo | Placebo comparator | matching placebo capsules to be taken twice daily Receives: Drug: Ursodiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Area Above Basal (AAB) for Glucose
Mixed meal glucose results are used to calculate the area above basal (AAB) for glucose. The glycemic index of a food is defined as the incremental area under the two-hour blood glucose response curve (AUC) following an overnight fast and ingestion of a food with a certain quantity of available carbohydrate (usually 50 g).
Measured: baseline, post-treatment approximately 14 - 17 days
Secondary outcomes (7)
Change in Fasting Glucose
Serum glucose measurements taken after 10 hours of fasting.
Measured: baseline, post-treatment approximately 14 - 17 days
Change in Insulin Sensitivity
Insulin sensitivity will be calculated by the oral minimal model.
Measured: baseline, post-treatment approximately 14 - 17 days
Gastric Emptying of Liquids (T1/2)
The time for half of the ingested liquids to leave the stomach. Following a meal with milk labeled with indium In111 diethylenetriaminepentaacetate (0.1 mCi), gastric emptying of liquids was assessed with scintigraphy imaging.
Measured: post-treatment, approximately 14-17 days
Gastric Emptying of Solids (T1/2)
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi) served with 50g of Canadian bacon and one slice of bread gastric emptying of solids was assessed with scintigraphy imaging.
Measured: post-treatment, approximately 14-17 days
Change in Weight
Change in subject's weight, in kilograms
Measured: baseline, post-treatment approximately 14 - 17 days
Change in Body Mass Index
Change in subjects BMI, in kilograms per meter squared.
Measured: baseline, post-treatment approximately 14 - 17 days
Change in FGF-19
Change in fasting fibroblast growth factor (FGF)-19 expression.
Measured: baseline, post-treatment approximately 14 - 17 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study startOct 2013
- Primary completionJan 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Camilleri, MD, Mayo Clinic
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02033876
- Sponsor's protocol ID
- 13-004908
- Status last verified
- Apr 2019
- First submitted
- 9 Jan 2014
- Last updated
- 8 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Calderon G, McRae A, Rievaj J, Davis J, Zandvakili I, Linker-Nord S, Burton D, Roberts G, Reimann F, Gedulin B, Vella A, LaRusso NF, Camilleri M, Gribble FM, Acosta A. Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes. EBioMedicine. 2020 May;55:102759. doi: 10.1016/j.ebiom.2020.102759. Epub 2020 Apr 25.
PubMed 32344198
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Delayed-Release Ursodeoxycholic Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes on Metformin Treatment
- ClinicalTrials.gov ID
- NCT02033876
- Acronym / sponsor ID
- 13-004908
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 13 Jan 2014 (estimated)
- Results
- Posted 8 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. These observations will provide the preliminary data for proposing future therapeutic as well as further mechanistic studies of the role of bile acids in the control of glycemia in T2DM.
Detailed description
Background: Intra-jejunal administration of bile acids improves insulin sensitivity.
Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release formulation, stimulates bile acid membrane receptor (TGR-5) and farnesol X (FXR) receptors in the ileum and colon, increasing the secretion of Fibroblast growth factor 19 (FGF-19), GLP-1, oxyntomodulin (OXM), and Peptide (PYY3-36), improving insulin sensitivity and inducing weight loss.
Aim: To study the effect of an ileocolonic formulation of UDCA on insulin sensitivity, postprandial plasma glycemia and incretin levels, gastric emptying and body weight in overweight or obese type 2 diabetic subjects on monotherapy with metformin.
Study design: This is a single center, placebo-controlled, parallel group, single dose randomized controlled trial to study the effect of delayed (ileocolonic)-release UDCA 600 mg twice daily on insulin sensitivity, gastric emptying of liquids and solids (measured by scintigraphy)and weight loss in overweight or obese type 2 diabetic subjects. Participants will be receiving monotherapy with metformin. Blood samples will be collected at defined times to measure glycemia and the incretin (GLP-1, OXM, PYY3-36) fasting levels and responses to the meal.
Anticipated Results: In comparison with placebo, UDCA will increase insulin sensitivity, enhance glycemic control, increase postprandial incretins, and delay gastric emptying (GE) of liquids.
Significance: This study will prove that ileocolonic-release UDCA enhances glycemic control in T2DM patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ursodiol | Experimental | Drug: UrsodiolUrsodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily |
| Placebo | Placebo comparator | Drug: Ursodiolmatching placebo capsules to be taken twice daily |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| UrsodiolAlso: Ursodeoxycholic acid | Drug | Placebo, Ursodiol |
Primary outcome
Change in Area Above Basal (AAB) for Glucose
Time frame: baseline, post-treatment approximately 14 - 17 days
Mixed meal glucose results are used to calculate the area above basal (AAB) for glucose. The glycemic index of a food is defined as the incremental area under the two-hour blood glucose response curve (AUC) following an overnight fast and ingestion of a food with a certain quantity of available carbohydrate (usually 50 g).
7 secondary outcomes
Change in Fasting Glucose
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in Insulin Sensitivity
Time frame: baseline, post-treatment approximately 14 - 17 days
Gastric Emptying of Liquids (T1/2)
Time frame: post-treatment, approximately 14-17 days
Gastric Emptying of Solids (T1/2)
Time frame: post-treatment, approximately 14-17 days
Change in Weight
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in Body Mass Index
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in FGF-19
Time frame: baseline, post-treatment approximately 14 - 17 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32344198Calderon G, McRae A, Rievaj J, Davis J, Zandvakili I, Linker-Nord S, Burton D, Roberts G, Reimann F, Gedulin B, Vella A, LaRusso NF, Camilleri M, Gribble FM, Acosta A. Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes. EBioMedicine. 2020 May;55:102759. doi: 10.1016/j.ebiom.2020.102759. Epub 2020 Apr 25.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Michael Camilleri, MD principal investigator
Mayo Clinic
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 Ursodiol in people with Type 2 Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 8 May 2019. 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 United States. 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?
Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Area Above Basal (AAB) for Glucose (time frame: baseline, post-treatment approximately 14 - 17 days). 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 NCT02033876, 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 8 May 2019.