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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

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

NCT ID

NCT00938405

First Posted

July 10, 2009

Last Updated

May 19, 2014

Sponsor

University of Colorado, Denver

Collaborators

Daiichi Sankyo, Inc.

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

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

Arm Title

Comparison group

Arm Type

Placebo Comparator

Arm Description

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

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

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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