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Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Satish K. Garg, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier:
NCT00938405
First received: July 10, 2009
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 1
Hyperlipidemias
Drug: Colesevelam HCl
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by University of Colorado Denver School of Medicine Barbara Davis Center:

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. [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]

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. [ Time Frame: 12 weeks of treatment. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • In addition change in insulin dose at one, two and three months from baseline will be evaluated. [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: July 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Colesevelam HCl
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.
Drug: Placebo
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00938405

Locations
United States, Colorado
Barbara Davis Center for Diabetes
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
Daiichi Sankyo Inc.
Investigators
Principal Investigator: Satish K Garg, MD University of Colorado Denver/ Barbara Davis Center for Diabetes
  More Information

Publications:
Responsible Party: Satish K. Garg, Professor of Medicine & Pediatrics, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT00938405     History of Changes
Other Study ID Numbers: DSI-WCH-100
Study First Received: July 10, 2009
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado Denver School of Medicine Barbara Davis Center:
type 1 diabetes mellitus
colesevelam
LDL
cholesterol
A1c
target range glucose values

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hyperlipidemias
Autoimmune Diseases
Dyslipidemias
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Colesevelam
Anticholesteremic Agents
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014