Type 2 Diabetes MellitusSeveXNCT03739268
GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration
A study testing Sevelamer in people with Type 2 Diabetes Mellitus, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
The objective of this study is to investigate the potential GLP-1-mediated contribution to the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration . Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Sevelamer
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2018to 1 Sep 2021
- 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 glucose-lowering drug
- Caucasian ethnicity
- Normal haemoglobin
- Age above 40 years and below 75 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- or hyperthyroidism
- Hypo- or hypercalcaemia
- Hypo- or hyperphosphataemia
Show all 11Show fewer
- 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.
Denmark1 site
Steno Diabetes Center Copenhagen, Gentofte Hospital
Hellerup, 2900
About this study
The objective of this study is to investigate the potential GLP-1-mediated contribution to the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration . Exendin9-39 has been demonstrated to act as a potent and specific GLP-1 receptor antagonist with no partial agonistic potential and is considered a useful tool in the assessment of GLP-1 physiology. The aim is to evaluate any contribution of sevelamer-induced GLP-1 secretion to the reduced plasma glucose concentrations observed after treatment with sevelamer. A randomised placebo-controlled cross-over study involving two 17-day treatment periods with sevelamer and placebo, respectively, in metformin-treated patients with type 2 diabetes, will be conducted. The impact of bile acid sequestration on GLP-1 secretion and effect will be examined during two randomised experimental days after 15 and 17 days of treatment with sevelamer (1,600 mg three times a day) and placebo, respectively. During each of these two experimental days, a meal test with concomitant exendin9-39 infusion or placebo will be performed (for evaluation of any GLP-1-mediated effects). Postprandial plasma glucose excursion is the primary endpoint, and secondary endpoints include postprandial plasma/serum excursions of insulin, C-peptide, GLP-1, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY (PYY), oxyntomodulin, ghrelin, fibroblast growth factor (FGF)-19, FGF-21, C4 (an intermediate in the de novo synthesis of bile acids), cholecystokinin (CCK), bile acids and plasma lipids. Furthermore, gastric emptying, gallbladder emptying, liver fat content, appetite and ad libitum food intake will be examined.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Sevelamer, Placebo
- Keywords
- bile acid
- 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
Also called Renvela
Sevelamer powder dissolved in water 1,600 mg three times a day for 17 days
PlaceboDrug
placebo powder dissolved in water 1,600 mg three times a day for 17 days
| Study group | Role | What they receive |
|---|---|---|
| sevelamer | Active comparator | Patients with type 2 diabetes treated with sevelamer Receives: Drug: Sevelamer |
| placebo | Placebo comparator | Patients with type 2 diabetes treated with placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma glucose
Postprandial plasma glucose (PG) excursion (AUC240 min)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Secondary outcomes (17)
Postprandial responses of glucagon-like peptide-1 (GLP-1)
Meal response of GLP-1
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of glucose-dependent insulinotropic polypeptide (GIP)
Meal response of glucose-dependent insulinotropic polypeptide (GIP)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of glucagon-like peptide-2 (GLP-2)
Meal response of glucagon-like peptide-2 (GLP-2)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Glucagon
Meal response of Glucagon
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of peptide YY (PYY)
Meal response of peptide YY (PYY)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Insulin and c-peptide
Meal response of Insulin and c-peptide as a insulin/c-peptide ratio
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Ghrelin
Meal response of Ghrelin
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of fibroblast growth factor (FGF)-19
Meal response of fibroblast growth factor (FGF)-19
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of fibroblast growth factor (FGF)-21
Meal response of fibroblast growth factor (FGF)-21
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Bile acids
Meal response of Bile acids
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of cholecystokinin (CCK)
Meal response of cholecystokinin (CCK)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of plasma lipids
Meal response of plasma lipids
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Amino acids
Meal response of Amino acids
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Gastric emptying
Gastric emptying measured by paracetamol absorption test. Paracetamol is ingested along with meal, the appearance in blood will be calculated as a measure of gastric emptying.
Measured: -30 minutes to 240 minutes with ingestion of a meal and paracetamol at 0 minutes
Rate of gall bladder emptying
Gall bladder volumen measured by ultrasound over time after a meal (see time frame below). The rate of gall bladder emptying will be calculated
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Liver stiffness and fat
Liver stiffness and fat content measured by fibroscan
Measured: At initiation and after 15 days of treatment with sevelamer/placebo
Appetite measured by visual analog scale
We assessed appetite parameters (hunger, satiety, fullness, prospective food consumption) and well-being, nausea, and thirst by visual analogue scales. Overall appetite score (OAS) will be calculated as (satiety + fullness + (100 - hunger) + (100 - prospective food consumption)
Measured: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start1 Sep 2018
- Primary completion3 Sep 2020
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Filip K Knop, M.D. PhD, Study director, Steno Diabetes Center CopenhagenHenriette H Nerild, M.D., Principal investigator, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03739268
- Sponsor's protocol ID
- SeveX2018
- Acronym
- SeveX
- Status last verified
- Sep 2020
- First submitted
- 11 Oct 2018
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration
- ClinicalTrials.gov ID
- NCT03739268
- Acronym / sponsor ID
- SeveX / SeveX2018
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- bile acid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 3 Sep 2020 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 13 Nov 2018 (actual)
- 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 objective of this study is to investigate the potential GLP-1-mediated contribution to the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration . Exendin9-39 has been demonstrated to act as a potent and specific GLP-1 receptor antagonist with no partial agonistic potential and is considered a useful tool in the assessment of GLP-1 physiology. The aim is to evaluate any contribution of sevelamer-induced GLP-1 secretion to the reduced plasma glucose concentrations observed after treatment with sevelamer. A randomised placebo-controlled cross-over study involving two 17-day treatment periods with sevelamer and placebo, respectively, in metformin-treated patients with type 2 diabetes, will be conducted. The impact of bile acid sequestration on GLP-1 secretion and effect will be examined during two randomised experimental days after 15 and 17 days of treatment with sevelamer (1,600 mg three times a day) and placebo, respectively. During each of these two experimental days, a meal test with concomitant exendin9-39 infusion or placebo will be performed (for evaluation of any GLP-1-mediated effects). Postprandial plasma glucose excursion is the primary endpoint, and secondary endpoints include postprandial plasma/serum excursions of insulin, C-peptide, GLP-1, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY (PYY), oxyntomodulin, ghrelin, fibroblast growth factor (FGF)-19, FGF-21, C4 (an intermediate in the de novo synthesis of bile acids), cholecystokinin (CCK), bile acids and plasma lipids. Furthermore, gastric emptying, gallbladder emptying, liver fat content, appetite and ad libitum food intake will be examined.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sevelamer | Active comparator | Drug: SevelamerPatients with type 2 diabetes treated with sevelamer |
| placebo | Placebo comparator | Drug: PlaceboPatients with type 2 diabetes treated with placebo |
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 glucose-lowering 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- or hyperthyroidism
- Hypo- or 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 |
|---|---|---|
| SevelamerAlso: RenvelaSevelamer powder dissolved in water 1,600 mg three times a day for 17 days | Drug | sevelamer |
| Placeboplacebo powder dissolved in water 1,600 mg three times a day for 17 days | Drug | placebo |
Primary outcome
plasma glucose
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial plasma glucose (PG) excursion (AUC240 min)
17 secondary outcomes
Postprandial responses of glucagon-like peptide-1 (GLP-1)
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of glucose-dependent insulinotropic polypeptide (GIP)
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of glucagon-like peptide-2 (GLP-2)
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Glucagon
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of peptide YY (PYY)
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Insulin and c-peptide
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Ghrelin
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of fibroblast growth factor (FGF)-19
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of fibroblast growth factor (FGF)-21
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Bile acids
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of cholecystokinin (CCK)
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of plasma lipids
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial responses of Amino acids
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Gastric emptying
Time frame: -30 minutes to 240 minutes with ingestion of a meal and paracetamol at 0 minutes
Rate of gall bladder emptying
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Liver stiffness and fat
Time frame: At initiation and after 15 days of treatment with sevelamer/placebo
Appetite measured by visual analog scale
Time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 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 13 Oct 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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.
Filip K Knop, M.D. PhD study director
Steno Diabetes Center Copenhagen
Henriette H Nerild, M.D. principal investigator
Steno Diabetes Center 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 Sevelamer in people with Type 2 Diabetes Mellitus, run by Steno Diabetes Center 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 13 Oct 2021. 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?
plasma glucose (time frame: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes). 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 13 Oct 2021.