Clinical trial NCT01092663: The Effects of Co-admin of Colesevelam and Sitagliptin on Glucose Metabolism in Subjects With Type 2 Diabetes Mellitus
Official title: The Effects of Co-administration of Colesevelam and Sitagliptin on Glucose Metabolism in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: Colesevelam
type 2 diabetes
sitagliptin
glucose metabolism
Lead sponsor: KineMed
Sponsor class: INDUSTRY
First posted: 2010-03-25
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the effects of colesevelam, alone or in combination with sitagliptin, on glucose metabolism in subjects with T2DM inadequately controlled by diet and exercise

Detailed description: The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by

1. improving the effects of colesevelam on fasting glucose metabolism
2. improving the effects of colsevelam on postprandial glucose metabolism

Eligibility criteria: Inclusion Criteria:

* Male or Female
* Females of childbearing potential are on approved birth control method
* Negative pregnancy testing for females of childbearing potential
* Previously diagnosed or newly diagnosed with T2DM drug naïve subjects
* HbA1c: 6.7-10%
* Age 18 - 80 years
* BMI ≥ 18.5 kg/m2 and ≤ 40 kg/m2
* Fasting serum glucose \< 300 mg/dL
* Normal liver function, normal thyroid function, no history of liver, biliary or intestinal disease
* Normal TSH
* On stable diet and exercise routine for at least 4 weeks prior to screening
* Has had a stable weight (+/-5%) for ≥3 months before screening

Exclusion Criteria:

* A history of type 1 diabetes mellitus or history of diabetic ketoacidosis
* History of chronic (required daily for \> 2 months) use of insulin therapy
* Treatment with blood pressure lowering therapy that has not been stable for three months before screening
* Treatment with lipid lowering medication other than statins
* Treatment with statins that has not been stable for three months before screening
* Treatment with a DPP-4 inhibitor or and GLP1 agonists at any time
* Treatment with a thiazolidinedione (TZD) within the last 6 months of screening
* History of an allergic or toxic reaction to sitagliptin or colesevelam
* History of dysphagia, swallowing disorders, bowel obstruction, intestinal motility disorder, and gastrointestinal disorders
* History of major gastrointestinal surgery
* History of kidney problems
* Fasting plasma triglycerides \> 300 mg/dL
* Serum LDL-C \<60 mg/dL
* Positive toxicology test
* Known hypersensitivity to colesevelam HCl or sitagliptin.
* Any contraindications to a study medication (colesevelam HCl or sitagliptin).

Primary outcomes:
measure: Hemoglobin A1C
timeFrame: Baseline and 12 weeks
measure: Fasting Plasma Glucose
timeFrame: Baseline and 12 weeks
measure: Fasting Endogenous Glucose Production
timeFrame: baseline and 12 weeks
measure: Fasting Gluconeogenesis
timeFrame: baseline and 12 weeks
measure: Fasting Glycogenolysis
timeFrame: baseline and 12 weeks
measure: Fasting Plasma Glucose Clearance
timeFrame: baseline and 12 weeks
measure: Appearance Rate of Oral Glucose
timeFrame: baseline and 12 weeks
measure: Postprandial Endogenous Glucose Production
timeFrame: baseline and 12 weeks
measure: Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC)
timeFrame: baseline and 12 weeks
measure: Whole-body Glycolytic Disposal of Oral Glucose
timeFrame: baseline and 12 weeks
measure: Postprandial Glucose (AUC)
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Fasting Plasma C-peptide
timeFrame: Baseline and 12 weeks
measure: Fasting Plamsa Glucagon
timeFrame: Baseline and 12 weeks
measure: Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1)
timeFrame: Baseline and 12 weeks
measure: Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP)
timeFrame: Baseline and 12 weeks
measure: Fasting Insulin
timeFrame: Baseline and 12 weeks
measure: Postprandial Insulin (AUC)
timeFrame: Baseline and 12 weeks
measure: Postprandial C-peptide (AUC)
timeFrame: Baseline and 12 weeks
measure: Postprandial Active GLP-1 (AUC)
timeFrame: Baseline and 12 weeks
measure: Postprandial Total GIP (AUC)
timeFrame: Baseline and 12 weeks
measure: Postprandial Glucagon (AUC)
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: San Antonio
country: United States
facility: Healthcare Discoveries, LLC d/b/a ICON Development Solutions
state: Texas
Study officials:
affiliation: KineMed, Inc.
name: Carine Beysen, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008 Oct 13;168(18):1975-83. doi: 10.1001/archinte.168.18.1975.
citation: Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care. 2008 Aug;31(8):1479-84. doi: 10.2337/dc08-0283. Epub 2008 May 5.
citation: Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008 Jul 28;168(14):1531-40. doi: 10.1001/archinte.168.14.1531.
citation: Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7. doi: 10.2337/dc06-0703.
citation: Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007 Mar;9(2):194-205. doi: 10.1111/j.1463-1326.2006.00704.x.
citation: Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007 Aug;30(8):1979-87. doi: 10.2337/dc07-0627. Epub 2007 May 7.