Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus

NCT00938405 | Completed

• 1 other identifier: DSI-WCH-100
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1; Hyperlipidemias

Keywords

type 1 diabetes mellitus; colesevelam; LDL; cholesterol; A1c; target range glucose values

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

Colesevelam HCl

EXPERIMENTAL

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

Comparison group

PLACEBO COMPARATOR

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

Interventions

Colesevelam HCl DRUG

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.

Also known as: WELCHOL (colesevelam hydrochloride), Initial U.S. Approval: 2000

Colesevelam HCl

Placebo DRUG

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.

Comparison group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• % ≤ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Related Publications (6)

• 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.

  PMID: 18852398 BACKGROUND

• 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.

  PMID: 18663165 BACKGROUND

• 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.

  PMID: 18458145 BACKGROUND

• 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.

  PMID: 19494473 BACKGROUND

• 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.

  PMID: 19494475 BACKGROUND

• 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.

  PMID: 17848608 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hyperlipidemias

Interventions

Colesevelam Hydrochloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Dyslipidemias; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons

Study Officials

• Satish K Garg, MD

  University of Colorado Denver/ Barbara Davis Center for Diabetes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine & Pediatrics

Study Record Dates

• First Submitted: July 10, 2009
• First Posted: July 13, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 20, 2014

Record last verified: 2014-05

Locations

US (1)