Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus
Efficacy of Colesevelam in Subjects With Type 1 Diabetes Mellitus
Sponsors
Lead Sponsor
Collaborators
Source
University of Colorado Denver School of Medicine Barbara Davis Center
Oversight Info
Has Dmc
No
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
45
Conditions
Intervention
Intervention Type
Drug
Intervention Name
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
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
Has Expanded Access
No
Condition Browse
Number Of Arms
2
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
Citation
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
Citation
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
Citation
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
Citation
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. Review.
PMID
19494473
Citation
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. Review.
PMID
19494475
Citation
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. Epub 2007 Sep 11.
PMID
17848608
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
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
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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.
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.