N/A N=60 Randomized Double-blind Basic Science

Mechanisms of Glucose Lowering Effect of Colesevelam HCl

Diabetes

Bottom Line

View on ClinicalTrials.gov: NCT00596427 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Oct 2012

Primary outcome: Primary: Fasting Endogenous Glucose Production (EGP) — 0.19; 1.59 umol per kg Fat-Free Mass (FFM) per min — p=<0.1

Study Design & Population

Study type: Interventional
Phase: N/A
Interventions: Colesevelam HCL (Drug); Placebo (Drug)
Age: Adult, Older Adult · 30+ yrs
Sex: All
Sponsor: Carine Beysen
Primary completion: Apr 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Fasting Endogenous Glucose Production (EGP)	0.19; 1.59	<0.1
PRIMARY Fasting Gluconeogenesis	0.02; -0.19	<0.1
PRIMARY Fasting Glycogenolysis	0.11; 1.78	0.05
PRIMARY Rate of Appearance of Exogenous Glucose (Glucose Absorption)	0; 1	0.6
SECONDARY Total Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)	5; -3	<0.01 sig
SECONDARY Total Glucose-dependent Insulinotropic Polypeptide (GIP) AUC	7; -6	<0.001 sig
SECONDARY Fasting Fractional De Novo Lipogenesis (DNL)	-0.6; -1.4	0.3
SECONDARY Fasting Fractional Cholesterol Synthesis	3.0; 0.5	<0.0001 sig
SECONDARY Postprandial Fractional Cholic Acid Synthesis	5.5; 1.7	<0.01 sig
SECONDARY Glucagon AUC	4; -4	<0.1

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.

Eligibility Criteria

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
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

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

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00596427). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.