Diabetes Mellitus, Type 2NCT02445508
Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
A study testing Sevelamer, Cholecystokinin and Isotonic saline in people with Diabetes Mellitus, Type 2, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Sevelamer, Cholecystokinin and Isotonic saline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteDenmark
- Study dates
- May 2015to Jul 2016
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))
- Men and postmenopausal women
- Metformin applied as the only anti-diabetic drug
- Caucasian ethnicity
- Normal haemoglobin
- Age above 40 years and below 70 years
- BMI >23 kg/m2 and <35 kg/m2
- Informed and written consent
Who cannot join
- Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
- Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
- Nephropathy (serum creatinine >150 µM and/or albuminuria)
- Hypo- and hyperthyroidism
- Hypo- and hypercalcaemia
- Hypo- and hyperphosphataemia
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- Active or recent malignant disease
- Treatment with medicine that cannot be paused for 12 hours
- Treatment with oral anticoagulants
- Any treatment or condition requiring acute or sub-acute medical or surgical intervention
- Any condition considered incompatible with participation by the investigators
Trial locations and contacts
1 site in 1 country.
About this study
Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis.
The current study is a human interventional randomized controlled cross-over study including four study days for each participant. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes.
The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Sevelamer, Cholecystokinin, Sevelamer placebo, Isotonic saline
- 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.
SevelamerDrug
CholecystokininDrug
Sevelamer placeboDrug
Isotonic salineDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo+Placebo | Placebo comparator | Oral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline. Receives: Drug: Sevelamer placebo; Drug: Isotonic saline |
| Placebo+Cholecystokinin | Active comparator | Oral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin. Receives: Drug: Cholecystokinin; Drug: Sevelamer placebo |
| Sevelamer+Placebo | Active comparator | Oral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline. Receives: Drug: Sevelamer; Drug: Isotonic saline |
| Sevelamer+Cholecystokinin | Active comparator | Oral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin. Receives: Drug: Sevelamer; Drug: Cholecystokinin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Measured: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Secondary outcomes (5)
Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Measured: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Blood analysis of paracetamol as an assessment of gastric emptying
Assessment of gastric emptying
Measured: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Indirect calorimetry: Basal metabolic rate
Basal metabolic rate
Measured: -30 min to 240 min
Gallbladder volume as assessed by Ultrasound measurements
Gallbladder volume
Measured: -30 min to 240 min
Appetite as assessed by Visual analog scale score
Appetite
Measured: -30 min to 240 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Principal investigator, Andreas Brønden, University Hospital, Gentofte, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445508
- Sponsor's protocol ID
- NCT02445508
- Status last verified
- May 2017
- First submitted
- 8 May 2015
- Last updated
- 3 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
- ClinicalTrials.gov ID
- NCT02445508
- Acronym / sponsor ID
- NCT02445508
- Conditions
- Diabetes Mellitus, Type 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- May 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 15 May 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.
Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis.
The current study is a human interventional randomized controlled cross-over study including four study days for each participant. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes.
The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo+Placebo | Placebo comparator | Drug: Sevelamer placebo, Drug: Isotonic salineOral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline. |
| Placebo+Cholecystokinin | Active comparator | Drug: Cholecystokinin, Drug: Sevelamer placeboOral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin. |
| Sevelamer+Placebo | Active comparator | Drug: Sevelamer, Drug: Isotonic salineOral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline. |
| Sevelamer+Cholecystokinin | Active comparator | Drug: Sevelamer, Drug: CholecystokininOral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))
- Men and postmenopausal women
- Metformin applied as the only anti-diabetic drug
- Caucasian ethnicity
- Normal haemoglobin
Key exclusion criteria (11 listed)
- Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
- Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
- Nephropathy (serum creatinine >150 µM and/or albuminuria)
- Hypo- and hyperthyroidism
- Hypo- and hypercalcaemia
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 |
|---|---|---|
| Sevelamer | Drug | Sevelamer+Cholecystokinin, Sevelamer+Placebo |
| Cholecystokinin | Drug | Placebo+Cholecystokinin, Sevelamer+Cholecystokinin |
| Sevelamer placebo | Drug | Placebo+Cholecystokinin, Placebo+Placebo |
| Isotonic saline | Drug | Placebo+Placebo, Sevelamer+Placebo |
Primary outcome
Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
5 secondary outcomes
Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Blood analysis of paracetamol as an assessment of gastric emptying
Time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4
Indirect calorimetry: Basal metabolic rate
Time frame: -30 min to 240 min
Gallbladder volume as assessed by Ultrasound measurements
Time frame: -30 min to 240 min
Appetite as assessed by Visual analog scale score
Time frame: -30 min to 240 min
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 3 May 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sevelamer, Cholecystokinin and Isotonic saline in people with Diabetes Mellitus, Type 2, 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 8 inclusion and 11 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 3 May 2017. 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. 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.
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?
Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve (time frame: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4). 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 3 May 2017.