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Type 2 DiabetesPhase 4NCT00951899

The Effect of Welchol on Glucose Metabolism in Type 2 Diabetics

A Phase 4 study testing Colesevelam, Diet and Metformin in people with Type 2 Diabetes, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this study was to determine the metabolic mechanism for a certain type medication's ability to lower blood sugar after a meal in Type 2 Diabetics, in order to develop a better understanding of it's potential role in the treatment of obesity. Read more about this study

Who is it for?
Ages 35 to 70 years
Conditions the study is for
Type 2 Diabetes
What is being tested?
Colesevelam, Diet and Metformin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
38 participants
Where
1 siteUnited States
Study dates
Aug 2009to Dec 2012
Phase
Phase 4
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 35 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 35-70 years old.
  • Body Mass Index greater than 19kg/m^2 or less than 40kg/m^2 or a total weight less than 130 kilograms.
  • Negative pregnancy test for women of childbearing potential.
  • Absence of gastrointestinal symptoms.
  • Signed informed consent.
  • Treatment with diet and/or metformin. Subjects must be on stable therapeutic doses of metformin and/or lipid-lowering agents for more than 3 months.

Who cannot join

  • Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. A screening Bowel Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome. Patients with a history of dysphagia or intestinal motility disorders will be excluded.
  • Prior history of pancreatitis.
  • Prior history of hypertriglyceridemia (500mg/dL or greater).
  • Currently using a bile-acid binding resin such as colesevelam, colestipol, colestimide or cholestyramine.
  • To ensure homogeneity between treatment groups we will exclude subjects with insulin-treated type 2 diabetes mellitus, subjects who have received an inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors) or "gliptins" (a class of oral hypoglycemics), Byetta or sulfonylurea agent in the past three months.
  • HbA1c greater than 9.0%.
Show all 14Show fewer
  • Patients who have not been stable on all medications for a period exceeding 3 months.
  • Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4 weeks during the study period that:
  • Alter GI transit including laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, Selective Serotonin Reuptake Inhibitors (SSRIs) and newer antidepressants.
  • Opiate-based analgesic drugs (Note: intermittent or chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAID) will be allowed).
  • Antihistamines
  • Anticholinergic agents
  • Female subjects who are pregnant or breast-feeding. Females must be either surgically sterilized, postmenopausal (>12 months since last menses), or, if of childbearing potential, using reliable methods of contraception as determined by the physician.
  • Clinical evidence (including physical exam and Electrocardiogram) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study. Any candidate participants with such disorders mentioned will be referred to their general physician.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: The Effect of Colesevelam Hydrochloride on Disposition Index and Incretin Concentrations in Subjects With Type 2 Diabetes Using a Double-blind, Placebo-controlled, Parallel-group Study Design

The goal of this study was to determine the metabolic mechanism for a certain type medication's ability to lower blood sugar after a meal in Type 2 Diabetics, in order to develop a better understanding of it's potential role in the treatment of obesity.

Read the detailed description

Welchol (colesevelam hydrochloride) is a bile acid sequestrant (BAS) recently approved by the FDA for glucose lowering in patients with type 2 diabetes mellitus. Four randomized, controlled clinical studies in subjects with type 2 diabetes have demonstrated significant treatment difference in HbA1c (-0.5%). Study durations ranged from 12-26 weeks of therapy. In diabetes clinical studies, a therapeutic response to colesevelam hydrochloride, as reflected by reduction in A1c was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment. Reductions in both fasting plasma glucose and postprandial concentrations have been demonstrated. Simple measures of insulin secretion and action have suggested that this is due to improved insulin action rather than improved insulin secretion. The mechanism by which bile acids interact with the key pathways regulating glucose concentrations is largely unknown. The investigators propose a randomized, double-blind, placebo controlled trial with a parallel-group design where subjects are randomized to receive colesevelam or matching placebo for a 12 week treatment period. A labeled mixed meal before and after treatment will be used to measure intestinal transit, postprandial and fasting glucose fluxes, insulin secretion and action as well as enteroendocrine secretion.

Conditions
Type 2 Diabetes
Being tested
Colesevelam, Placebo, Diet, Metformin
Keywords
Incretins, colesevelam, hepatobiliary circulation
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.

  • ColesevelamDrug

    Also called Welchol

    Colesevelam hydrochloride; three 625mg tablets taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period.

  • PlaceboOther

    Three placebo tablets matching the active drug colesevelam in appearance, taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period.

  • DietBehavioural

    Subjects were instructed to follow a weight maintenance diet (~55% carbohydrate, 30% fat and 15% protein) for the 12 week study period.

  • MetforminDrug

    Also called Glucophage, Glucophage XR, Glumetza, Fortamet

    Subjects continued to take their pre-study therapeutic doses of metformin (Metformin 500mg tablets taken by mouth twice daily for a total daily dose of 1000 to 2000 mg) through the 12 week study period.

Study groups in NCT00951899
Study groupRoleWhat they receive
ColesevelamExperimentalTreatment with colesevelam hydrochloride in addition to Metformin and Diet
Receives: Drug: Colesevelam; Behavioral: Diet; Drug: Metformin
PlaceboPlacebo comparatorTreatment with placebo in addition to Metformin and Diet
Receives: Other: Placebo; Behavioral: Diet; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Disposition Index

    Total Disposition Index (DI) is a calculated value which represents the ability of a person's pancreas to lower blood glucose. A higher number means the pancreas is better able to lower blood glucose and a lower number means the pancreas is less able to lower blood glucose.

    Measured: Baseline, 12 weeks

Secondary outcomes (8)

  1. Total Fasting Glucagon-Like Peptide-1 (GLP-1) Concentration

    GLP-1 is thought to increase insulin secretion and was measured in the blood and reported in picomoles per liter.

    Measured: Baseline, 12 weeks

  2. Plasma Glucose Concentration

    Fasting glucose concentrations were measured at baseline and 2 hours post-meal using the glucose oxidase method.

    Measured: Baseline, 12 Weeks

  3. Glycosylated Hemoglobin (HbA1c)

    HbA1c is the percent of red blood cell hemoglobin with glucose attached to it and an indicator of average blood glucose over the previous two to three months.

    Measured: Baseline, 12 weeks

  4. Insulin Concentration

    Fasting insulin levels were measured in the plasma using a chemiluminescence assay and is reported in nanomoles over 6 hours.

    Measured: Baseline, 12 Weeks

  5. Fasting Endogenous Glucose Production (EGP)

    EGP was measured using a triple-tracer mixed meal and calculated using the Steele's model, reported in micromoles per kilogram per minute.

    Measured: Baseline, 12 Weeks

  6. Rate of Meal Glucose Appearance (Meal Ra)

    Meal Ra was measured using a triple-tracer mixed meal and reported in micromols in 6 hours. Meal derived glucose is a function of both gastric emptying and splanchnic meal extraction. Meal Ra was calculated by multiplying rate of appearance of [1-^13C] glucose (obtained from the infusion rate of [6-^3H] glucose and the clamped plasma ratio of [6-^3H] glucose and [1-^13C] glucose) by the meal enrichment.

    Measured: Baseline, 12 Weeks

  7. Rate of Meal Glucose Disappearance (Meal Rd)

    Meal Rd is the rate at which glucose leaves the systemic circulation. It was measured using a triple-tracer mixed meal and reported in micromols over 6 hours. Meal Rd was calculated by subtracting the change in glucose mass from the overall rate of glucose appearance (i.e., meal Ra + EGP).

    Measured: Baseline, 12 Weeks

  8. Lipid Values

    Lipids are fat-like substances in the blood.

    Measured: Baseline, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionJul 2012
  4. Study completionDec 2012

Resources

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 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00951899
Sponsor's protocol ID
08-008284
Other IDs
R01DK078646, R01DK082396, UL1RR024150
Status last verified
Oct 2013
First submitted
31 Jul 2009
Last updated
11 Nov 2013
Data monitoring committee
Yes

Publications

  • Smushkin G, Sathananthan M, Piccinini F, Dalla Man C, Law JH, Cobelli C, Zinsmeister AR, Rizza RA, Vella A. The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes. 2013 Apr;62(4):1094-101. doi: 10.2337/db12-0923. Epub 2012 Dec 18.

    PubMed 23250357

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Colesevelam, Diet and Metformin in people with Type 2 Diabetes, run by Mayo Clinic at 1 site in United States.

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 6 inclusion and 14 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 11 Nov 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 United States. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 15 Aug 2013). 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?

Total Disposition Index (time frame: Baseline, 12 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 NCT00951899, 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 11 Nov 2013.

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