Type 2 DiabetesNCT01666223
Effect of Bile Acids on GLP-1 Secretion
A study testing Colesevelam, Chenodeoxycholic Acid and saline in people with Type 2 Diabetes and Obesity, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes, Obesity
- What is being tested?
- Colesevelam, Chenodeoxycholic Acid and saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2012to Jun 2013
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- danish caucasian ethnicity
- normal haemoglobin
- BMI > 25 kg/m2
- HbA1c < 9%
- informed consent
- danish caucasian ethnicity
Show all 9Show fewer
- normal haemoglobin
- HbA1c < 6,0 (American Diabetes Association guidelines)
- informed consent
Who cannot join
- liver disease(ALT and AST > upper reference limit)
- gastrointestinal disease
- liver and biliary tract disease
- nephropathy (serum creatinine > 150 μM, and/or albuminuria)
- treatment with insulin, glp-1 analogues and/ or DPP-4 inhibitors
- treatment with medicine that can not be paused for 12 hours
Show all 18Show fewer
- previous abdominal surgery eg. cholecystectomy
- BMI < 18,5 kg/m2 or > 35 kg/m2
- Healthy Volunteers
- liver disease(ALT and AST > upper reference limit)
- gastrointestinal disease
- liver and biliary tract disease
- nephropathy (serum creatinine > 150 μM, and/or albuminuria)
- treatment with medicine that can not be paused for 12 hours
- previous abdominal surgery eg. cholecystectomy
- BMI < 18,5 kg/m2 or > 35 kg/m2
- first degree relatives diagnosed with diabetes
- previously diagnosed with diabetes, or treated with antidiabetic agents
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
Hellerup, Copenhagen
About this study
Official title: Effect of Bile Acids in the Gut on GLP-1 Secretion in Healthy Subjects and Patients With Type 2 Diabetes
The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.
Read the detailed description
The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.
- Conditions
- Type 2 Diabetes, Obesity
- Being tested
- Colesevelam, Chenodeoxycholic Acid, saline, Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg
- Keywords
- Type 2 diabetes, GLP-1, Bile acid, TGR-5
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColesevelamDrug
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
Chenodeoxycholic AcidDrug
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
salineOther
100 ml saline
Colesevelam 3750 mg + chenodeoxycholic acid 1250 mgDrug
Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.
| Study group | Role | What they receive |
|---|---|---|
| Colesevelam | Experimental | Not described Receives: Drug: Colesevelam |
| Chenodeoxycholic acid | Experimental | Not described Receives: Drug: Chenodeoxycholic Acid |
| Colesevelam + chenodeoxycholic acid | Experimental | Not described Receives: Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg |
| Placebo | Experimental | Not described Receives: Other: saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in GLP-1
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Secondary outcomes (14)
Change in insulin
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in C-peptide
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon-like-peptide 2 (GLP-2)
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucose-dependent insulinotropic polypeptide (GIP)
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in peptide YY (PYY)
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in oxyntomodulin
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in bile acids
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in gastrin
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in CCK
Measured: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in appetite, satiety and prospective food consumption
Evaluated by Visual Analog Scale (VAS)
Measured: At baseline, and 30, 60, 90, 120 and 180 minutes
Change in gallbladder volume
Evaluated by ultrasound
Measured: -30, 0 (baseline), 30, 60, 120 og 180 minutes
Change in basal metabolic rate
Evaluated by indirect calorimetry
Measured: At -30, 60 og 150 minutes
Change in bile acid composition
Evaluated by duodenal aspiration
Measured: At -30, 0, 30, 60, 120 og 180 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2012 (estimated)
- Study startNov 2012
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Morten Hansen, University Hospital, Gentofte, Copenhagen
- Investigators
- Morten Hansen, MD, Principal investigator, Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01666223
- Sponsor's protocol ID
- H-1-2012-049
- Status last verified
- Dec 2013
- First submitted
- 11 Jul 2012
- Last updated
- 24 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. doi: 10.1016/s0006-291x(02)02550-0.
PubMed 12419312Adrian TE, Ballantyne GH, Longo WE, Bilchik AJ, Graham S, Basson MD, Tierney RP, Modlin IM. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993 Sep;34(9):1219-24. doi: 10.1136/gut.34.9.1219.
PubMed 8406158Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90. doi: 10.1016/j.bbrc.2005.01.139.
PubMed 15721318Rafferty EP, Wylie AR, Hand KH, Elliott CE, Grieve DJ, Green BD. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice. Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 27.
PubMed 21521075
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Bile Acids in the Gut on GLP-1 Secretion in Healthy Subjects and Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01666223
- Acronym / sponsor ID
- H-1-2012-049
- Conditions
- Type 2 Diabetes, Obesity
- Keywords
- Type 2 diabetes, GLP-1, Bile acid, TGR-5
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 Aug 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.
The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.
Detailed description
The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Colesevelam | Experimental | Drug: Colesevelam |
| Chenodeoxycholic acid | Experimental | Drug: Chenodeoxycholic Acid |
| Colesevelam + chenodeoxycholic acid | Experimental | Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg |
| Placebo | Experimental | Other: saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- danish caucasian ethnicity
- normal haemoglobin
- BMI > 25 kg/m2
- HbA1c < 9%
- informed consent
Key exclusion criteria (18 listed)
- liver disease(ALT and AST > upper reference limit)
- gastrointestinal disease
- liver and biliary tract disease
- nephropathy (serum creatinine > 150 μM, and/or albuminuria)
- treatment with insulin, glp-1 analogues and/ or DPP-4 inhibitors
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 |
|---|---|---|
| ColesevelamColesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0. | Drug | Colesevelam |
| Chenodeoxycholic Acid1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0. | Drug | Chenodeoxycholic acid |
| saline100 ml saline | Other | Placebo |
| Colesevelam 3750 mg + chenodeoxycholic acid 1250 mgColesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0. | Drug | Colesevelam + chenodeoxycholic acid |
Primary outcome
Change in GLP-1
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
14 secondary outcomes
Change in insulin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in C-peptide
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon-like-peptide 2 (GLP-2)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucose-dependent insulinotropic polypeptide (GIP)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in peptide YY (PYY)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in oxyntomodulin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in bile acids
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in gastrin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in CCK
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in appetite, satiety and prospective food consumption
Time frame: At baseline, and 30, 60, 90, 120 and 180 minutes
Change in gallbladder volume
Time frame: -30, 0 (baseline), 30, 60, 120 og 180 minutes
Change in basal metabolic rate
Time frame: At -30, 60 og 150 minutes
Change in bile acid composition
Time frame: At -30, 0, 30, 60, 120 og 180 minutes
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 24 Dec 2013.
- Background: PubMed 12419312Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002 Nov 15;298(5):714-9. doi: 10.1016/s0006-291x(02)02550-0.
- Background: PubMed 8406158Adrian TE, Ballantyne GH, Longo WE, Bilchik AJ, Graham S, Basson MD, Tierney RP, Modlin IM. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993 Sep;34(9):1219-24. doi: 10.1136/gut.34.9.1219.
- Background: PubMed 15721318Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005 Apr 1;329(1):386-90. doi: 10.1016/j.bbrc.2005.01.139.
- Background: PubMed 21521075Rafferty EP, Wylie AR, Hand KH, Elliott CE, Grieve DJ, Green BD. Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice. Biol Chem. 2011 Apr;392(6):539-46. doi: 10.1515/BC.2011.050. Epub 2011 Apr 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.
Morten Hansen, MD principal investigator
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Colesevelam, Chenodeoxycholic Acid and saline in people with Type 2 Diabetes and Obesity, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
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 9 inclusion and 18 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 24 Dec 2013. 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 Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Change in GLP-1 (time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes). 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 NCT01666223, which also lists 4 linked publications.
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 24 Dec 2013.