Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

Sponsor

University of Colorado, Denver (Other)

Overall Status

Completed

CT.gov ID

NCT00938405

Collaborator

Daiichi Sankyo, Inc. (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1 Hyperlipidemias	Drug: Colesevelam HCl Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

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.	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.

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.

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.

Outcome Measures

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. [12 weeks of treatment]

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. [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. [12 weeks of treatment.]
In addition change in insulin dose at one, two and three months from baseline will be evaluated. [12 weeks of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.