To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 SecretionNCT01656057
The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
A study testing Acetaminophen, Metformin and Colesevelam in people with To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion, run by Filip Krag Knop at 1 site in Denmark.
Trial summary
The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion
- What is being tested?
- Acetaminophen, Metformin and Colesevelam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- Jul 2012to Apr 2014
- 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 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- HbA1c < 6,0%
- Not anaemic
- Written informed consent
Who cannot join
- Liver disease
- Nephropathy
- fasting plasma glucose > 5,6mM
- Diabetes running in the family (parents or grandparents)
- Any medical treatment
- A former medical history of liver- or bile disease
- any surgical procedure conducted in the abdomen
- Body mass index < 18,5 kg/m2 or > 25 kg/m2
Trial locations and contacts
1 site in 1 country.
Denmark1 site
University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
Copenhagen, Hellerup, 2900
About this study
The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain.
The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant ("a bile acid binder") will further enhance this GLP-1 response.
- Being tested
- Acetaminophen, Metformin, Colesevelam, Cholecystokinin-8, Saline
- Keywords
- Bile acids, Gall bladder emptying, Human, Glucagon like peptide 1, GLP-1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Paracetamol
Acetaminophen dissolved in 50 ml of water
MetforminDrug
Metformin + acetaminophen dissolved in 50 ml of water
ColesevelamDrug
Colesevelam + acetaminophen dissolved in 50 ml of water
Cholecystokinin-8Other
Also called CCK-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
SalineOther
iv. saline infusion 40 ml/hour for the first 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen+saline | Experimental | Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Receives: Drug: Acetaminophen; Other: Saline |
| Acetaminophen+CCK | Experimental | Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Receives: Drug: Acetaminophen; Other: Cholecystokinin-8 |
| Metformin+saline | Experimental | Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Receives: Drug: Acetaminophen; Drug: Metformin; Other: Saline |
| Metformin+CCK | Experimental | Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Receives: Drug: Acetaminophen; Drug: Metformin; Other: Cholecystokinin-8 |
| Colesevelam+saline | Experimental | Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline Receives: Drug: Acetaminophen; Drug: Colesevelam; Other: Saline |
| Colesevelam+CCK | Experimental | Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Receives: Drug: Acetaminophen; Drug: Colesevelam; Other: Cholecystokinin-8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
GLP-1 response as incremental area under curve (iAUC)
Measured: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Secondary outcomes (1)
Insulin
Measured: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionOct 2013
- Study completionApr 2014
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 To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 SecretionStudies 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
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Filip Krag Knop
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor-investigator, Filip Krag Knop, University Hospital, Gentofte, Copenhagen
- Investigators
- Ulrich Rohde, MD, Principal investigator, Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656057
- Sponsor's protocol ID
- GALINKUR
- Status last verified
- Jul 2015
- First submitted
- 31 Jul 2012
- Last updated
- 14 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Rohde U, Sonne DP, Christensen M, Hansen M, Bronden A, Torang S, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses. J Clin Endocrinol Metab. 2016 May;101(5):2076-83. doi: 10.1210/jc.2016-1133. Epub 2016 Mar 22.
PubMed 27003305
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
- ClinicalTrials.gov ID
- NCT01656057
- Acronym / sponsor ID
- GALINKUR
- Keywords
- Bile acids, Gall bladder emptying, Human, Glucagon like peptide 1, GLP-1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Filip Krag KnopUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- Jul 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 2 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 last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain.
The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant ("a bile acid binder") will further enhance this GLP-1 response.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen+saline | Experimental | Drug: Acetaminophen, Other: SalineAcetaminophen tablet 1500 mg via nasogastric tube + i.v. saline |
| Acetaminophen+CCK | Experimental | Drug: Acetaminophen, Other: Cholecystokinin-8Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour |
| Metformin+saline | Experimental | Drug: Acetaminophen, Drug: Metformin, Other: SalineMetformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline |
| Metformin+CCK | Experimental | Drug: Acetaminophen, Drug: Metformin, Other: Cholecystokinin-8Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour |
| Colesevelam+saline | Experimental | Drug: Acetaminophen, Drug: Colesevelam, Other: SalineColesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline |
| Colesevelam+CCK | Experimental | Drug: Acetaminophen, Drug: Colesevelam, Other: Cholecystokinin-8Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- HbA1c < 6,0%
- Not anaemic
- Written informed consent
Key exclusion criteria (8 listed)
- Liver disease
- Nephropathy
- fasting plasma glucose > 5,6mM
- Diabetes running in the family (parents or grandparents)
- Any medical treatment
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 |
|---|---|---|
| AcetaminophenAlso: ParacetamolAcetaminophen dissolved in 50 ml of water | Drug | Acetaminophen+CCK, Acetaminophen+saline, Colesevelam+CCK, Colesevelam+saline, Metformin+CCK, Metformin+saline |
| MetforminMetformin + acetaminophen dissolved in 50 ml of water | Drug | Metformin+CCK, Metformin+saline |
| ColesevelamColesevelam + acetaminophen dissolved in 50 ml of water | Drug | Colesevelam+CCK, Colesevelam+saline |
| Cholecystokinin-8Also: CCK-8iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes | Other | Acetaminophen+CCK, Colesevelam+CCK, Metformin+CCK |
| Salineiv. saline infusion 40 ml/hour for the first 60 minutes | Other | Acetaminophen+saline, Colesevelam+saline, Metformin+saline |
Primary outcome
GLP-1 response as incremental area under curve (iAUC)
Time frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
1 secondary outcome
Insulin
Time frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
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 14 Jul 2015.
- Derived from this study: PubMed 27003305Rohde U, Sonne DP, Christensen M, Hansen M, Bronden A, Torang S, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses. J Clin Endocrinol Metab. 2016 May;101(5):2076-83. doi: 10.1210/jc.2016-1133. Epub 2016 Mar 22.
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.
Ulrich Rohde, MD principal investigator
Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetaminophen, Metformin and Colesevelam in people with To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion, run by Filip Krag Knop 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 3 inclusion and 8 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 14 Jul 2015. 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?
GLP-1 response as incremental area under curve (iAUC) (time frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240). 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 NCT01656057, 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 14 Jul 2015.