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Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

Primary Purpose

Diabetes Mellitus, Type 1, Hyperlipidemias

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Colesevelam HCl
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring type 1 diabetes mellitus, colesevelam, LDL, cholesterol, A1c, target range glucose values

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • All subjects will be on stable doses of insulin using MDI or CSII (Basal insulin- Lantus or Levemir; Bolus- Humalog, Novolog, Apidra, Humulin Regular), for three months prior to enrollment.
  • Type 1 diabetes duration > 3 years.
  • 6.5% ≤ A1c ≤ 9.0%.
  • Male or female ≥ 18 and ≤ 65 years of age.
  • Ability and willingness to adhere to the protocol including multiple daily oral doses of study drug or placebo and week-long CGM wear.
  • LDL-C > 100 mg/dl.
  • Willing to adhere to colesevelam dosage instructions, including administration of drugs with a known interaction at least 4 hours prior to colesevelam. Females using oral contraceptives containing ethinyl estradiol and norethindrone must be willing to administer their doses at least four hours prior to using colesevelam.

Exclusion Criteria:

  • Advanced retinopathy needing laser procedure or vitrectomy.
  • Unstable nephropathy (serum creatinine > 2.0 mg/dl or macroproteinuria (albumin excretion rate > 200 ug/ min).
  • Any unexplained severe hypoglycemia within the last six months.
  • BMI > 35.0.
  • Currently on a pre-existing bile acid sequestrant therapy, glyburide, levothyroxine, phenytoin, or warfarin.
  • Pregnant, planning a pregnancy, or not using an adequate method of birth control.
  • Any other condition, as determined by the investigator, which could make the subject unsuitable for the trial, impairs the subject's suitability for the trial, or impairs the validity of the informed consent.
  • Use of any medication known to modify glucose values other than insulin (i.e. corticosteroids or oral antidiabetics).
  • A history of bowel obstruction.
  • Serum triglyceride (TG) concentrations >500 mg/dL.
  • A history of hypertriglyceridemia induced pancreatitis.

Sites / Locations

  • Barbara Davis Center for Diabetes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Colesevelam HCl

Comparison group

Arm Description

Beginning at Visit 1, two weeks after screening, subjects in the active treatment group will take 3.75 gms/day of colesevelam HCl in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.

Beginning at Visit 1, two weeks after screening, subjects in the comparison group will be administered placebo, taking 3.75 gms/day of colesevelam HCl in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.

Outcomes

Primary Outcome Measures

To demonstrate a 10% LDL reduction in type 1 diabetic subjects with initial LDL > 100 after twelve weeks in the colesevelam group.

Secondary Outcome Measures

To evaluate colesevelam use for glucose control as measured by A1c using a 0.4% confidence interval at baseline and after one, two, and three months of therapy.
To evaluate colesevelam use for non-inferiority of percent of target range glucose values and time spent in hyper- and hypoglycemic ranges as determined by CGM readings at baseline and after one, two, and three months of therapy.
In addition change in insulin dose at one, two and three months from baseline will be evaluated.

Full Information

First Posted
July 10, 2009
Last Updated
May 19, 2014
Sponsor
University of Colorado, Denver
Collaborators
Daiichi Sankyo, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00938405
Brief Title
Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus
Official Title
Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Colorado, Denver
Collaborators
Daiichi Sankyo, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, randomized, double blind, parallel, placebo controlled clinical trial evaluating the efficacy of colesevelam HCl in reducing LDL in subjects with type 1 diabetes mellitus over a 12 week treatment period. The aim is to highlight the effect of colesevelam on LDL cholesterol and glycemia in a type 1 diabetic population. The colesevelam group is anticipated to demonstrate a mean reduction in LDL by 10% compared to the placebo group, indicated by A1c and glycemic target range CGM readings.
Detailed Description
This is a prospective, randomized, double blind, parallel, placebo controlled clinical trial evaluating the efficacy of colesevelam HCl in reducing LDL in subjects with type 1 diabetes mellitus over a 12 week treatment period. Colesevelam is an orally administered bile acid sequestrant approved as an adjunct for diet and exercise for lowering incidence of hyperlipidemia, an important risk factor for long term cardiovascular health in the general population and people living with diabetes. Use of colesevelam has been shown to concurrently decrease low density lipoprotein cholesterol (LDL-C) and A1c in patients with type 2 diabetes. The exact mechanism is unknown. Our research aims to highlight the effect of colesevelam on LDL and glycemia in a type 1 diabetic population. This single-center study will enroll a maximum of 40 patients with LDL-C > 100 and A1c values between 6.5-9%, who will be randomized in a 1:1 fashion to either the study drug or placebo. Visits will be conducted at screening, baseline, one month, two months, and three months. At home, subjects will take 3.75 gms/day of colesevelam HCl or placebo throughout the study duration. Laboratory analysis will be performed at various timepoints assessing A1c, fasting lipid panel, c-peptide, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP). Continuous glucose monitoring (CGM) measurements will be obtained on all patients for one week before each monthly visit to assess for above target range (ATR), within target range (WTR), and below target range (BTR) glucose values and time spent in hyperglycemic and hypoglycemic excursions. The colesevelam group is anticipated to demonstrate a mean reduction in LDL by 10% compared to the placebo group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1, Hyperlipidemias
Keywords
type 1 diabetes mellitus, colesevelam, LDL, cholesterol, A1c, target range glucose values

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Colesevelam HCl
Arm Type
Experimental
Arm Description
Beginning at Visit 1, two weeks after screening, subjects in the active treatment group will take 3.75 gms/day of colesevelam HCl in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.
Arm Title
Comparison group
Arm Type
Placebo Comparator
Arm Description
Beginning at Visit 1, two weeks after screening, subjects in the comparison group will be administered placebo, taking 3.75 gms/day of colesevelam HCl in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.
Intervention Type
Drug
Intervention Name(s)
Colesevelam HCl
Other Intervention Name(s)
WELCHOL (colesevelam hydrochloride), Initial U.S. Approval: 2000
Intervention Description
3.75 gms/day of colesevelam HCl in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo: 3.75 gms/day in the form of three 625 mg tablets with lunch and dinner or six 625mg tablets once daily with dinner.
Primary Outcome Measure Information:
Title
To demonstrate a 10% LDL reduction in type 1 diabetic subjects with initial LDL > 100 after twelve weeks in the colesevelam group.
Time Frame
12 weeks of treatment
Secondary Outcome Measure Information:
Title
To evaluate colesevelam use for glucose control as measured by A1c using a 0.4% confidence interval at baseline and after one, two, and three months of therapy.
Time Frame
12 weeks of treatment.
Title
To evaluate colesevelam use for non-inferiority of percent of target range glucose values and time spent in hyper- and hypoglycemic ranges as determined by CGM readings at baseline and after one, two, and three months of therapy.
Time Frame
12 weeks of treatment.
Title
In addition change in insulin dose at one, two and three months from baseline will be evaluated.
Time Frame
12 weeks of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: All subjects will be on stable doses of insulin using MDI or CSII (Basal insulin- Lantus or Levemir; Bolus- Humalog, Novolog, Apidra, Humulin Regular), for three months prior to enrollment. Type 1 diabetes duration > 3 years. 6.5% ≤ A1c ≤ 9.0%. Male or female ≥ 18 and ≤ 65 years of age. Ability and willingness to adhere to the protocol including multiple daily oral doses of study drug or placebo and week-long CGM wear. LDL-C > 100 mg/dl. Willing to adhere to colesevelam dosage instructions, including administration of drugs with a known interaction at least 4 hours prior to colesevelam. Females using oral contraceptives containing ethinyl estradiol and norethindrone must be willing to administer their doses at least four hours prior to using colesevelam. Exclusion Criteria: Advanced retinopathy needing laser procedure or vitrectomy. Unstable nephropathy (serum creatinine > 2.0 mg/dl or macroproteinuria (albumin excretion rate > 200 ug/ min). Any unexplained severe hypoglycemia within the last six months. BMI > 35.0. Currently on a pre-existing bile acid sequestrant therapy, glyburide, levothyroxine, phenytoin, or warfarin. Pregnant, planning a pregnancy, or not using an adequate method of birth control. Any other condition, as determined by the investigator, which could make the subject unsuitable for the trial, impairs the subject's suitability for the trial, or impairs the validity of the informed consent. Use of any medication known to modify glucose values other than insulin (i.e. corticosteroids or oral antidiabetics). A history of bowel obstruction. Serum triglyceride (TG) concentrations >500 mg/dL. A history of hypertriglyceridemia induced pancreatitis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Satish K Garg, MD
Organizational Affiliation
University of Colorado Denver/ Barbara Davis Center for Diabetes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Davis Center for Diabetes
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18852398
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.
Results Reference
background
PubMed Identifier
18663165
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.
Results Reference
background
PubMed Identifier
18458145
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.
Results Reference
background
PubMed Identifier
19494473
Citation
Goldfine AB, Fonseca VA. The use of colesevelam HCl in patients with type 2 diabetes mellitus: combining glucose- and lipid-lowering effects. Postgrad Med. 2009 May;121(3 Suppl 1):13-8. doi: 10.3810/pgm.2009.05.suppl53.288.
Results Reference
background
PubMed Identifier
19494475
Citation
Staels B. A review of bile acid sequestrants: potential mechanism(s) for glucose-lowering effects in type 2 diabetes mellitus. Postgrad Med. 2009 May;121(3 Suppl 1):25-30. doi: 10.3810/pgm.2009.05.suppl53.290.
Results Reference
background
PubMed Identifier
17848608
Citation
Garg SK, Kelly WC, Voelmle MK, Ritchie PJ, Gottlieb PA, McFann KK, Ellis SL. Continuous home monitoring of glucose: improved glycemic control with real-life use of continuous glucose sensors in adult subjects with type 1 diabetes. Diabetes Care. 2007 Dec;30(12):3023-5. doi: 10.2337/dc07-1436. Epub 2007 Sep 11. No abstract available.
Results Reference
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Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

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