Impaired Fasting GlucosePhase 3NCT00990184
Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
A Phase 3 study testing Colesevelam in people with Impaired Fasting Glucose and Prediabetes, run by Seattle Institute for Biomedical and Clinical Research.
Trial summary
The objective of this study is to determine the effect of 8 weeks of treatment with colesevelam HCl 3.75 g once daily with the evening meal on ß-cell function by evaluating the acute insulin response (AIRg) to an intravenous glucose load in subjects with prediabetes (impaired fasting glucose). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Impaired Fasting Glucose, Prediabetes
- What is being tested?
- Colesevelam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- No sites listed yet
- Study dates
- Sep 2009to Oct 2010
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females (postmenopausal, surgically sterile or using double-barrier method of contraception), aged 18-75 years, FPG 100-115 mg/dl at screening (average of 2 measurements during screening; no individual measurement outside of the range 92-125 mg/dl)
- In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis
- HbA1c <6.5% at screening
- Body mass index (BMI) in the range of 22-40 kg/m2 inclusive and with a stable (+/-2.5 kg) weight for the last 6 months
- Subjects must be willing to:
- Maintain prior exercise and dietary habits throughout the study
- Comply with all study requirements
- Provide written informed consent
Who cannot join
- Pregnant or lactating females
- Patients diagnosed with type 2 diabetes or that have taken glucose-lowering agents or insulin, except during pregnancy
- Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 8 weeks prior to screening
- HIV protease inhibitors
- Warfarin or phenytoin use
- Triglycerides >500 mg/dl
Show all 16Show fewer
- History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
- History of dysphagia, swallowing disorders or intestinal motility disorder
- History of pancreatitis
- Uncontrolled hypothyroidism
- Individuals with clinical hepatic disease or liver function tests greater than ≥2 times upper limits of normal within 30 days preceding the first dose of study drug
- On a weight loss program with ongoing weight loss, or starting an intensive exercise program within 4 weeks of study initiation
- Current or prior (within the past 3 months) treatment with a bile acid sequestrant (colesevelam, colestipol, colestimide, or cholestyramine)
- Use of any investigational drug in the last 30 days
- Donation of one unit (500 ml) or more of blood, significant blood loss equaling at least one unit of blood within the past 2 weeks or a blood transfusion within 8 weeks prior to screening
- Employment by the research center
About this study
Official title: A Single-Blind Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
The objective of this study is to determine the effect of 8 weeks of treatment with colesevelam HCl 3.75 g once daily with the evening meal on ß-cell function by evaluating the acute insulin response (AIRg) to an intravenous glucose load in subjects with prediabetes (impaired fasting glucose).
Read the detailed description
Colesevelam is a bile acid sequestrant that was initially approved for treatment of patients with dyslipidemia. Subsequently it was observed that patients with type 2 diabetes receiving this medication had improved glucose control. However, the mechanism(s) by which it lowers glucose concentrations has not been determined.
Glucose metabolism is enhanced following oral nutrient ingestion by the action of the incretin hormones. The two major incretin hormones are the peptides glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are released from the intestinal tract wall in response to a meal. Of these two peptides, GLP-1 appears to be more important in regulating glucose metabolism. In the presence of elevated plasma glucose, GLP-1 promotes insulin release from the ß-cells of the pancreas. GLP-1 also suppresses glucagon release, and thereby inhibits hepatic glucose output. Administration of GLP-1 by infusion or by subcutaneous injection has been shown to improve glucose tolerance in type 2 diabetic patients.
The purpose of this study is therefore to determine in a cohort of individuals with prediabetes, who have an elevated fasting plasma glucose and are at increased risk of developing type 2 diabetes, whether the glucose lowering properties of colesevelam occur by it improving insulin sensitivity, islet ß-cell function or both. Further, by assessing the effect of colesevelam on incretin hormone release, it will be possible to determine whether any improvement in islet ß-cell function is due to enhanced incretin stimulation.
- Conditions
- Impaired Fasting Glucose, Prediabetes
- Being tested
- Colesevelam, placebo
- Keywords
- Impaired Fasting Glucose, PreDiabetes
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColesevelamDrug
Also called colesevelam HCl
colesevelam HCl 3.75 g once daily orally with the evening meal
placeboOther
tablet (s) orally given with evening meal
| Study group | Role | What they receive |
|---|---|---|
| Colesevelam Hydrochloride | Experimental | Not described Receives: Drug: Colesevelam; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Insulin Response (AIRg) to Intravenous Glucose
Increase in insulin following glucose injection. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection calculated over the 10 minutes following glucose administration.
Measured: Baseline and 8 weeks
Secondary outcomes (2)
Insulin Sensitivity
Tissue response to circulating insulin in the blood. Insulin sensitivity is measured using a mathematical model that quantifies the fractional rate of change in glucose concentrations per unit of insulin. Low values are insulin resistant and high values are insulin sensitive. *Please note: the "-1" in the Unit of Measure should be a superscripted value.
Measured: Baseline and 8 weeks
Glucose Disappearance Rate
Rate of fall of glucose in the blood
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionOct 2010
- Study completionOct 2010
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 Impaired Fasting GlucoseStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Institute for Biomedical and Clinical Research
- Sponsor type
- University, hospital or other
- Collaborators
- VA Puget Sound Health Care System
- Responsible party
- Sponsor
- Investigators
- Steven E Kahn, MB CHB, Principal investigator, VA Puget Sound Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00990184
- Sponsor's protocol ID
- 1.2
- Status last verified
- Oct 2012
- First submitted
- 2 Oct 2009
- Last updated
- 21 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Marina AL, Utzschneider KM, Wright LA, Montgomery BK, Marcovina SM, Kahn SE. Colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and beta-cell function. Diabetes Care. 2012 May;35(5):1119-25. doi: 10.2337/dc11-2050. Epub 2012 Mar 23.
PubMed 22446171
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Blind Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
- ClinicalTrials.gov ID
- NCT00990184
- Acronym / sponsor ID
- 1.2
- Conditions
- Impaired Fasting Glucose, Prediabetes
- Keywords
- Impaired Fasting Glucose, PreDiabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Seattle Institute for Biomedical and Clinical ResearchUniversity, hospital or other
- Collaborators
- VA Puget Sound Health Care System
- Study start
- Sep 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 6 Oct 2009 (estimated)
- Results
- Posted 21 Nov 2012
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 determine the effect of 8 weeks of treatment with colesevelam HCl 3.75 g once daily with the evening meal on ß-cell function by evaluating the acute insulin response (AIRg) to an intravenous glucose load in subjects with prediabetes (impaired fasting glucose).
Detailed description
Colesevelam is a bile acid sequestrant that was initially approved for treatment of patients with dyslipidemia. Subsequently it was observed that patients with type 2 diabetes receiving this medication had improved glucose control. However, the mechanism(s) by which it lowers glucose concentrations has not been determined.
Glucose metabolism is enhanced following oral nutrient ingestion by the action of the incretin hormones. The two major incretin hormones are the peptides glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are released from the intestinal tract wall in response to a meal. Of these two peptides, GLP-1 appears to be more important in regulating glucose metabolism. In the presence of elevated plasma glucose, GLP-1 promotes insulin release from the ß-cells of the pancreas. GLP-1 also suppresses glucagon release, and thereby inhibits hepatic glucose output. Administration of GLP-1 by infusion or by subcutaneous injection has been shown to improve glucose tolerance in type 2 diabetic patients.
The purpose of this study is therefore to determine in a cohort of individuals with prediabetes, who have an elevated fasting plasma glucose and are at increased risk of developing type 2 diabetes, whether the glucose lowering properties of colesevelam occur by it improving insulin sensitivity, islet ß-cell function or both. Further, by assessing the effect of colesevelam on incretin hormone release, it will be possible to determine whether any improvement in islet ß-cell function is due to enhanced incretin stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Colesevelam Hydrochloride | Experimental | Drug: Colesevelam, Other: placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females (postmenopausal, surgically sterile or using double-barrier method of contraception), aged 18-75 years, FPG 100-115 mg/dl at screening (average of 2 measurements during screening; no individual measurement outside of the range 92-125 mg/dl)
- In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis
- HbA1c <6.5% at screening
- Body mass index (BMI) in the range of 22-40 kg/m2 inclusive and with a stable (+/-2.5 kg) weight for the last 6 months
- Subjects must be willing to:
Key exclusion criteria (16 listed)
- Pregnant or lactating females
- Patients diagnosed with type 2 diabetes or that have taken glucose-lowering agents or insulin, except during pregnancy
- Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 8 weeks prior to screening
- HIV protease inhibitors
- Warfarin or phenytoin use
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 |
|---|---|---|
| ColesevelamAlso: colesevelam HClcolesevelam HCl 3.75 g once daily orally with the evening meal | Drug | Colesevelam Hydrochloride |
| placebotablet (s) orally given with evening meal | Other | Colesevelam Hydrochloride |
Primary outcome
Acute Insulin Response (AIRg) to Intravenous Glucose
Time frame: Baseline and 8 weeks
Increase in insulin following glucose injection. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection calculated over the 10 minutes following glucose administration.
2 secondary outcomes
Insulin Sensitivity
Time frame: Baseline and 8 weeks
Glucose Disappearance Rate
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22446171Marina AL, Utzschneider KM, Wright LA, Montgomery BK, Marcovina SM, Kahn SE. Colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and beta-cell function. Diabetes Care. 2012 May;35(5):1119-25. doi: 10.2337/dc11-2050. Epub 2012 Mar 23.
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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.
Steven E Kahn, MB CHB principal investigator
VA Puget Sound Health Care System
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Colesevelam in people with Impaired Fasting Glucose and Prediabetes, run by Seattle Institute for Biomedical and Clinical Research.
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 16 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 21 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 21 Nov 2012). 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?
Acute Insulin Response (AIRg) to Intravenous Glucose (time frame: Baseline and 8 weeks). 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 NCT00990184, 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 21 Nov 2012.