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CompletedNCT00596427Updated Oct 12, 2012Results posted

Mechanisms of Glucose Lowering Effect of Colesevelam HCl

An interventional study of Colesevelam HCL and Placebo in Diabetes, sponsored by Carine Beysen. Completed at 3 sites in United States. Open to participants aged 30 Years to 70 Years. Per ClinicalTrials.gov, last updated 2012-10-12.

Sponsored by Carine Beysen · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
30 Years to 70 Years
Sex
All
01

Study summary

The mechanism by which colesevelam HCl lowers glucose is not known. Knowledge of the potential mechanism of action is important for defining the role of the drug among oral antidiabetic agents available for use in subjects with diabetes. The objective of this study is to provide insight into the mechanisms of action of colesevelam HCl in T2DM. The mechanisms of interest include hepatic insulin sensitivity, rate of appearance of exogenous glucose and changes in incretin hormone concentrations.

Read the detailed description

Colesevelam HCl (marketed in the U.S. as WelChol®) is a non-absorbed polymer that binds bile acids in the intestine, impeding their reabsorption, and is indicated to lower low-density lipoprotein cholesterol (LDL-C) in subjects with hypercholesterolemia. As the bile acid pool becomes depleted, the hepatic enzyme cholesterol 7-(alpha)-hydroxylase is upregulated, increasing the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase, and increasing the number of hepatic low-density lipoprotein (LDL) receptors. These compensatory effects increase the clearance of LDL-C from the blood, decreasing serum LDL C levels (1; 2).

Recently, it has been shown that colesevelam HCl also improves glycemic control in subjects with T2DM who are not controlled adequately on metformin, sulfonylurea or a combination of the two drugs (3). The mechanism of action for glucose lowering is not known. Improved glycemic control with colesevelam HCl treatment could be due to any of several mechanisms. Colesevelam HCl could reduce hepatic insulin resistance and lead to a decrease in hepatic glucose production (HGP). The observation by Schwartz et al (4) of significantly reduced fasting plasma glucose concentrations in colesevelam-treated T2DM patients suggests such a reduction in HGP, as fasting hyperglycemia is a direct function of HGP. Colesevelam HCl could also decrease post-prandial glucose absorption. Changes in glucose absorption with other bile acid sequestrants (BAS) (5) and bile acids (6) have been reported.

With regard to molecular mediators of the colesevelam effect on glucose metabolism, there is considerable evidence emerging about the role of bile acids and nuclear transcription factors, such as the farnesyl X receptor (FXR), in the regulation of glucose and lipid metabolism (7) (8) (9-15). Changes in cellular lipids or nuclear hormone receptors might directly alter HGP although mechanisms leading to changes in hepatic lipid and glucose metabolism by colesevelam HCl have not previously been investigated.

Significant changes in cholesterol and bile acid synthesis rates are expected with colesevelam treatment. BAS treatment can alter the transhepatic flux and compositional profile of the circulating bile acid pool (16), and thus its hydrophobicity, and this may effect the activation of nuclear receptors, including FXR (17; 18). Determination of the effect of colesevelam treatment on bile acid synthesis may provide evidence for its metabolic effects. The effects on hepatic fatty acid synthesis (de novo lipogenesis or DNL) have not been investigated and may provide further evidence for a metabolic effect of colesevelam.

Specific hypotheses about its mode of action will be tested, focusing on hepatic glucose metabolism and intestinal glucose absorption.

02

Conditions studied

  • Diabetes

Keywords

  • type two diabetes
  • gluconeogenesis
  • glucose
  • lipid synthesis
  • hepatic insulin sensitivity
  • colesevelam HCl
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 60 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

This is the only study on the registry with Carine Beysen as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Subjects meeting the following criteria at the Screening Visit will be eligible to participate in the trial:

  • Have given written informed consent

  • Male or Female

    1. Females of childbearing potential who are on approved birth control method:

      oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide or female condom plus spermicide

    2. Females of non-childbearing potential: hysterectomy, tubal ligation 6 months prior screening or post-menopausal for at least 1 year
  • Previously diagnosed or newly diagnosed with T2DM
  • Age 30 to 70 years, inclusive
  • BMI ≥ 18.5 kg/m2 and ≤ 40 kg/m2
  • HbA1C 7-10%, inclusive (exceptions between 6.7-7% may be enrolled with prior approval of SPONSOR)
  • Fasting plasma glucose \< 300 mg/dL
  • Diet controlled or on stable dose of a sulfonylurea and/or meglitinides and/or metformin for ≥ 90 days before screening
  • No history of liver, biliary or intestinal disease (AST/ALT \< 2X upper limit of normal value)
  • Normal TSH
  • Agrees to maintain their regular diet and exercise routine
  • Agrees to refrain from consumption of alcohol 48 hours prior to start of infusions (week 0 and week 12)

Exclusion criteria

Exclusion Criteria:

Subjects are excluded from participation in the study if any of the following criteria apply:

  • Type 1 diabetes mellitus or history of diabetic ketoacidosis
  • Treatment with lipid lowering medication other than statins
  • Treatment with statins that have not been stable for 3 months before screening
  • Treatment with colesevelam HCl, cholestyramine or colestipol for hyperlipidemia within the last 3 months of screening
  • Treatment with a thiazolidinedione (TZD) at any time
  • Treatment with acarbose at any time
  • Treatment with insulin in the past 6 months
  • Treatment with antibiotics within the last 3 months
  • Treatment with any medication affecting liver or intestinal function within the last 3 months
  • Pregnant
  • Breastfeeding
  • Has had unstable weight within the last 3 months of screening (± 5 kg)
  • History of an allergic or toxic reaction to colesevelam HCl
  • History of dysphagia, swallowing disorders, or intestinal motility disorder
  • Serum triglycerides ≥ 350 mg/dL at screening visit (exceptions up to 500 mg/dl may be enrolled with prior approval of SPONSOR)
  • Serum LDL-C \<60 mg/dL at screening visit
  • Any condition or therapy which, in the opinion of the investigator, poses a risk to the subject or makes participation not in the subject's best interest
  • Use of any investigational drug within 3 months of screening
  • Chronic treatment with oral corticosteroids at any time or acute treatment within the last 3 months
  • History of drug or alcohol abuse, is currently a user (including "recreational use") of any illicit drugs, or has a positive urine drug screen at screening
  • Donated a unit of blood within 30 days before screening
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
60 participants (actual)

Study arms

  • Placebo comparator
    Placebo tablet 3 tablets 2x/day

    Type-2 diabetes mellitus patients

    Drug: Placebo

  • Experimental
    Colesevelam HCL 625 mg: 3 tablets 2x/day

    Type-2 diabetes mellitus patients

    Drug: Colesevelam HCL

Interventions

  • DrugColesevelam HCL

    Colesevelam HCL 625 mg: 3 tablets twice per day

    Also known as: WelChol

  • DrugPlacebo

    Placebo tablets: 3 tablets twice per day

06

What researchers measure

Primary outcomes

  1. Fasting Endogenous Glucose Production (EGP)

    Changes from baseline of fasting EGP after 12 weeks of placebo or colesevelam treatment.

    Time frame: baseline and 12 weeks

  2. Fasting Gluconeogenesis

    Change from baseline of fasting gluconeogenesis after 12 weeks of placebo or colesevelam treatment.

    Time frame: baseline and 12 weeks

  3. Fasting Glycogenolysis

    Change from baseline of fasting glycogenolysis after 12 weeks of placebo or colesevelam treatment.

    Time frame: baseline and 12 weeks

  4. Rate of Appearance of Exogenous Glucose (Glucose Absorption)

    Change from baseline of the rate of appearance of oral glucose after 12 weeks of placebo or colesevelam treatment. Mean of values obtained between 0 and 300 min is reported.

    Time frame: baseline and 12 weeks

Secondary outcomes

  1. Total Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)

    Changes from baseline of total GLP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

    Time frame: baseline and 12 weeks

  2. Total Glucose-dependent Insulinotropic Polypeptide (GIP) AUC

    Changes from baseline of total GIP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

    Time frame: baseline and 12 weeks

  3. Fasting Fractional De Novo Lipogenesis (DNL)

    Changes from baseline in fasting fractional DNL after 12 weeks of colesevelam or placebo treatment were calculated. Fractional DNL represents the fraction of palmitate in very-low density lipoproteins-triglycerides (VLDL-TG) that was newly synthesized.

    Time frame: baseline and 12 weeks

  4. Fasting Fractional Cholesterol Synthesis

    Changes from baseline in fasting fractional cholesterol synthesis after 12 weeks of colesevelam or placebo treatment. Fractional Cholesterol synthesis represents the fraction of free cholesterol in plasma that was newly synthesised.

    Time frame: baseline and 12 weeks

  5. Postprandial Fractional Cholic Acid Synthesis

    Changes from baseline in fractional cholic acid synthesis after 12 weeks of colesevelam or placebo treatment were evaluated. Fractional cholic acid synthesis represents the relative amount of cholic acid that is made from newly synthesised cholesterol.

    Time frame: baseline and 12 weeks

  6. Glucagon AUC

    Changes from baseline of glucagon AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

    Time frame: baseline and 12 weeks

Other outcomes

  1. Glycosylated Hemoglobin (HbAlc)

    Changes from baseline of HbA1c after 12 weeks of placebo or colesevelam treatment.

    Time frame: baseline and 12 weeks

  2. Glucose AUC

    Changes from baseline of glucose AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

    Time frame: baseline and 12 weeks

07

Results

Posted Oct 12, 2012

Participant flow

Participants with type 2 diabetes. All pre-existing drug treatments were stable for at least 3 months prior.

Participant flow — Overall Study
MilestoneType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Started3030
Completed2628
Not completed42
Withdrew: Withdrawal by subject22
Withdrew: Increased fasting triacylglycerol level10
Withdrew: Protocol violation10

Outcome measures

SecondaryTotal Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)

Changes from baseline of total GLP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

Time frame:
baseline and 12 weeks
Reported as:
Mean · picomoles (pmol)/Liter (L) x minute (min
Total Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)
picomoles (pmol)/Liter (L) x minute (minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Total Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)5 ± 2-3 ± 1
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.01
SecondaryTotal Glucose-dependent Insulinotropic Polypeptide (GIP) AUC

Changes from baseline of total GIP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

Time frame:
baseline and 12 weeks
Reported as:
Mean · pmol/l x min
Total Glucose-dependent Insulinotropic Polypeptide (GIP) AUC
pmol/l x minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Total Glucose-dependent Insulinotropic Polypeptide (GIP) AUC7 ± 2-6 ± 2
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.001
PrimaryFasting Endogenous Glucose Production (EGP)

Changes from baseline of fasting EGP after 12 weeks of placebo or colesevelam treatment.

Time frame:
baseline and 12 weeks
Reported as:
Mean · umol per kg Fat-Free Mass (FFM) per min
Fasting Endogenous Glucose Production (EGP)
umol per kg Fat-Free Mass (FFM) per minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Fasting Endogenous Glucose Production (EGP)0.19 ± 0.781.59 ± 0.77
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.1This model had fixed effects of treatment, visit and treatment by visit interaction and a random subject effect.
Other pre-specifiedGlycosylated Hemoglobin (HbAlc)

Changes from baseline of HbA1c after 12 weeks of placebo or colesevelam treatment.

Time frame:
baseline and 12 weeks
Reported as:
Mean · percentage
Glycosylated Hemoglobin (HbAlc)
percentageType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Glycosylated Hemoglobin (HbAlc)-0.3 ± 0.20.3 ± 0.2
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.01
Other pre-specifiedGlucose AUC

Changes from baseline of glucose AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

Time frame:
baseline and 12 weeks
Reported as:
Mean · millimoles (mmol)/l x min
Glucose AUC
millimoles (mmol)/l x minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Glucose AUC-0.8 ± 0.40.5 ± 0.4
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.05
PrimaryFasting Gluconeogenesis

Change from baseline of fasting gluconeogenesis after 12 weeks of placebo or colesevelam treatment.

Time frame:
baseline and 12 weeks
Reported as:
Mean · micromoles (µmol) per kg FFM per min
Fasting Gluconeogenesis
micromoles (µmol) per kg FFM per minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Fasting Gluconeogenesis0.02 ± 0.32-0.19 ± 0.27
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.1
PrimaryFasting Glycogenolysis

Change from baseline of fasting glycogenolysis after 12 weeks of placebo or colesevelam treatment.

Time frame:
baseline and 12 weeks
Reported as:
Mean · µmol per kilograms (kg) FFM per min
Fasting Glycogenolysis
µmol per kilograms (kg) FFM per minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Fasting Glycogenolysis0.11 ± 0.811.78 ± 0.69
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = 0.05
PrimaryRate of Appearance of Exogenous Glucose (Glucose Absorption)

Change from baseline of the rate of appearance of oral glucose after 12 weeks of placebo or colesevelam treatment. Mean of values obtained between 0 and 300 min is reported.

Time frame:
baseline and 12 weeks
Reported as:
Mean · µmol per kg FFM per minute (min)
Rate of Appearance of Exogenous Glucose (Glucose Absorption)
µmol per kg FFM per minute (min)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Rate of Appearance of Exogenous Glucose (Glucose Absorption)0 ± 0.561 ± 0.63
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = 0.6
SecondaryFasting Fractional De Novo Lipogenesis (DNL)

Changes from baseline in fasting fractional DNL after 12 weeks of colesevelam or placebo treatment were calculated. Fractional DNL represents the fraction of palmitate in very-low density lipoproteins-triglycerides (VLDL-TG) that was newly synthesized.

Time frame:
baseline and 12 weeks
Reported as:
Mean · percent new palmitate
Fasting Fractional De Novo Lipogenesis (DNL)
percent new palmitateType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Fasting Fractional De Novo Lipogenesis (DNL)-0.6 ± 0.57-1.4 ± 0.58
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam · mixed-effects regression models · p = 0.3
SecondaryFasting Fractional Cholesterol Synthesis

Changes from baseline in fasting fractional cholesterol synthesis after 12 weeks of colesevelam or placebo treatment. Fractional Cholesterol synthesis represents the fraction of free cholesterol in plasma that was newly synthesised.

Time frame:
baseline and 12 weeks
Reported as:
Mean · Percent new cholesterol
Fasting Fractional Cholesterol Synthesis
Percent new cholesterolType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Fasting Fractional Cholesterol Synthesis3.0 ± 0.40.5 ± 0.4
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam · mixed-effects regression models · p = <0.0001
SecondaryPostprandial Fractional Cholic Acid Synthesis

Changes from baseline in fractional cholic acid synthesis after 12 weeks of colesevelam or placebo treatment were evaluated. Fractional cholic acid synthesis represents the relative amount of cholic acid that is made from newly synthesised cholesterol.

Time frame:
baseline and 12 weeks
Reported as:
Mean · Percent new cholic acid
Postprandial Fractional Cholic Acid Synthesis
Percent new cholic acidType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Postprandial Fractional Cholic Acid Synthesis5.5 ± 1.01.7 ± 1.0
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam · mixed-effects regression models · p = <0.01
SecondaryGlucagon AUC

Changes from baseline of glucagon AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes

Time frame:
baseline and 12 weeks
Reported as:
Mean · picograms (pg)/milliter (ml) x min
Glucagon AUC
picograms (pg)/milliter (ml) x minType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
Glucagon AUC4 ± 3-4 ± 4
Statistical analysis
  • Type-2 Diabetes Mellitus Patients Treated With Colesevelam vs Type-2 Diabetes Mellitus Patients Treated With Placebo · mixed-effects regression models · p = <0.1

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 3.57% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Type-2 Diabetes Mellitus Patients Treated With Colesevelam—0/30 (0%)19/26 (73.1%)
Type-2 Diabetes Mellitus Patients Treated With Placebo—0/30 (0%)23/28 (82.1%)
Most frequent other events
Showing 10 of 17
Most frequent other events
EventType-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With Placebo
DiarrheaGastrointestinal disorders0/265/28
NauseaGastrointestinal disorders3/265/28
HeadacheNervous system disorders4/265/28
CoughRespiratory, thoracic and mediastinal disorders2/261/28
LethargicMusculoskeletal and connective tissue disorders2/260/28
DyspepsiaGastrointestinal disorders0/262/28
Sinus congestionRespiratory, thoracic and mediastinal disorders0/262/28
Abdominal crampsGastrointestinal disorders1/260/28
ConstipationGastrointestinal disorders1/261/28
Chest congestionRespiratory, thoracic and mediastinal disorders1/260/28

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
<=18 years000
Between 18 and 65 years242549
>=65 years6511
Age Continuous
Age Continuous(years)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Mean59 ± 956 ± 957.5 ± 9
Sex: Female, Male
Sex: Female, Male(Participants)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Female121426
Male181634
Region of Enrollment
Region of Enrollment(participants)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
United States303060
BMI
BMI(kg/m2)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Mean30 ± 531 ± 530.5 ± 5
Weight
Weight(kg)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Mean84 ± 1688 ± 1986 ± 18
HbA 1c
HbA 1c(percentage)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Mean8.5 ± 1.28.0 ± 0.98.25 ± 1.05
Glucose
Glucose(mmol/l)Type-2 Diabetes Mellitus Patients Treated With ColesevelamType-2 Diabetes Mellitus Patients Treated With PlaceboTotal
Mean9.2 ± 2.38.4 ± 2.48.8 ± 2.3

5 further baseline measures are reported on the registry.

08

Study locations

3 sites
  • Diablo Clinical Research, Inc
    Walnut Creek, California 94598, United States
  • Clinical Pharmacology of Miami, Inc
    Miami, Florida 33014, United States
  • Diabetes & Glandular Disease Research Associates
    San Antonio, Texas 78229, United States
09

References and documents

Publications

  • Grundy SM, Ahrens EH Jr, Salen G. Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism. J Lab Clin Med. 1971 Jul;78(1):94-121. No abstract available. PubMed 5569253 ↗
  • Shepherd J, Packard CJ, Bicker S, Lawrie TD, Morgan HG. Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism. N Engl J Med. 1980 May 29;302(22):1219-22. doi: 10.1056/NEJM198005293022202. PubMed 7366673 ↗
  • Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007 Jan;29(1):74-83. doi: 10.1016/j.clinthera.2007.01.003. PubMed 17379048 ↗
  • Jenkins DJ, Wolever TM, Leeds AR, Gassull MA, Haisman P, Dilawari J, Goff DV, Metz GL, Alberti KG. Dietary fibres, fibre analogues, and glucose tolerance: importance of viscosity. Br Med J. 1978 May 27;1(6124):1392-4. doi: 10.1136/bmj.1.6124.1392. PubMed 647304 ↗
  • Beysen C, Murphy EJ, Deines K, Chan M, Tsang E, Glass A, Turner SM, Protasio J, Riiff T, Hellerstein MK. Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study. Diabetologia. 2012 Feb;55(2):432-42. doi: 10.1007/s00125-011-2382-3. Epub 2011 Dec 2. PubMed 22134839 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 12, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00596427
Lead sponsor
Carine Beysen
Responsible party
Carine Beysen (Director, Clinical Metabolic Research, KineMed) — Sponsor-investigator
First posted
Jan 17, 2008
Start date
Nov 2007
Primary completion
Apr 2009
Completion
Apr 2009
Results posted
Oct 12, 2012
Last update
Oct 12, 2012

Study contacts

Carine Beysen, PhD
principal investigator · KineMed

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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