Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

Lead Sponsor

University of Colorado Denver School of Medicine Barbara Davis Center

Collaborators

Daiichi Sankyo, Inc.

Source

University of Colorado Denver School of Medicine Barbara Davis Center

Oversight Info

Has Dmc

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.

Overall Status

Completed

Start Date

2009-07-01

Completion Date

2009-12-01

Primary Completion Date

2009-12-01

Phase

N/A

Study Type

Interventional

Primary 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.	12 weeks of treatment

Secondary 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.	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

Enrollment

Conditions

Diabetes Mellitus, Type 1

, Hyperlipidemias

Intervention

Intervention Type

Drug

Intervention Name

Colesevelam HCl

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.

Arm Group Label

Colesevelam HCl

Other Name

WELCHOL (colesevelam hydrochloride)

Initial U.S. Approval: 2000

Intervention Type

Drug

Intervention Name

Placebo

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.

Arm Group Label

Comparison group

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.

Gender

All

Minimum Age

18 Years

Maximum Age

65 Years

Healthy Volunteers

Accepts Healthy Volunteers

Overall Official

Last Name	Role	Affiliation
Satish K Garg, MD	Principal Investigator	University of Colorado Denver/ Barbara Davis Center for Diabetes

Location

Facility

Barbara Davis Center for Diabetes
Aurora Colorado 80045 United States

Location Countries

Country

United States

Verification Date

2014-05-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Colorado Denver School of Medicine Barbara Davis Center

Investigator Full Name

Satish K. Garg

Investigator Title

Professor of Medicine & Pediatrics

Keywords

type 1 diabetes mellitus

, colesevelam

, LDL

, cholesterol

, A1c

, target range glucose values

Has Expanded Access

Condition Browse

Diabetes Mellitus

, Diabetes Mellitus, Type 1

, Hyperlipidemias

Number Of Arms

Intervention Browse

Mesh Term

Colesevelam Hydrochloride

Arm Group

Arm Group Label

Colesevelam HCl

Arm Group Type

Experimental

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 Group Label

Comparison group

Arm Group Type

Placebo Comparator

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.

Firstreceived Results Date

N/A

Reference

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Double (Participant, Investigator)

Study First Submitted

July 10, 2009

Study First Submitted Qc

July 10, 2009

Study First Posted

July 13, 2009

Last Update Submitted

May 19, 2014

Last Update Submitted Qc

May 19, 2014

Last Update Posted

May 20, 2014

ClinicalTrials.gov processed this data on December 06, 2019

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.

Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.

Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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