Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

May 19, 2014 updated by: Satish K. Garg, University of Colorado, Denver
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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Colorado
      • Aurora, Colorado, United States, 80045
        • Barbara Davis Center for Diabetes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Colesevelam HCl
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.
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.
Other Names:
  • WELCHOL (colesevelam hydrochloride)
  • Initial U.S. Approval: 2000
Placebo Comparator: Comparison group
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
12 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
12 weeks of treatment.
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.
12 weeks of treatment.
In addition change in insulin dose at one, two and three months from baseline will be evaluated.
Time Frame: 12 weeks of treatment
12 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Satish K Garg, MD, University of Colorado Denver/ Barbara Davis Center for Diabetes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

July 10, 2009

First Submitted That Met QC Criteria

July 10, 2009

First Posted (Estimate)

July 13, 2009

Study Record Updates

Last Update Posted (Estimate)

May 20, 2014

Last Update Submitted That Met QC Criteria

May 19, 2014

Last Verified

May 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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