Dyslipidemia, Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes Mellitus, dyslipidemia, adolescents
Brief summary
The purpose of the study is to establish the safety of ezetimibe/simvastatin and simvastatin in adolescents with Type 1 Diabetes and to determine the amount of decrease in LDL-cholesterol.The study hypothesizes that simvastatin and ezetimibe/simvastatin will be safe in adolescents with Type 1 Diabetes and will lower LDL-cholesterol at 6 months.
Detailed description
Cardiovascular disease is the leading cause of death in people with type 1 diabetes mellitus (T1DM) and since atherosclerosis begins in childhood, data to inform clinicians as to appropriate dyslipidemia treatment in this high-risk population are of great public health importance. In this trial of lipid-lowering medications (Zocor \[simvastatin\], a statin, compared to Vytorin \[ezetimibe/simvastatin\], a combination of a statin and Zetia, a medication that blocks cholesterol absorption) will be performed in patients ages 12-18 years with LDL ≥ 130 mg/dl, consistent with current ADA guidelines. The study hypothesizes that Zocor and Vytorin will be safe in adolescents with T1DM and will lower LDL-cholesterol at 6 months compared to baseline. In a two-arm design, Vytorin will lower LDL-c more than monotherapy with Zocor.
Interventions
DRUGSimvastatin
simvastatin 20 mg daily
Ezetimibe (10mg)/Simvastatin (20mg)
Sponsors
Merck Sharp & Dohme LLC
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* 12-18 years of age with Type 1 Diabetes and seen at the Barbara Davis Center for Childhood Diabetes * Positive diabetes auto-antibodies or provider diagnosed Type 1 Diabetes * LDL \> 130 mg/dl.
Exclusion criteria
* Familial hypercholesterolemia, Triglycerides (TG) \> 400mg/dl * Type 1 Diabetes of less than three-month duration * HbA1c\>9.5% * Abnormal thyroid function * Abnormal Creatine Kinase (CK) values (defined as \> 10 times the upper limit of normal) * Abnormal liver function tests (ALT/AST) (defined as \>3 times the upper limit of normal) * Pregnancy, and patients on oral contraceptives * All resources are in English. Spanish speakers will not be available for the follow-up calls.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor. | Baseline to 6 months | Change in LDL-c between Zocor and Vytorin treatment in subjects with Type 1 Diabetes measured at baseline to the 6-month study visit. |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment: baseline 12/20/07-2/9/10; all participants completed 6-month trial by 8/3/10. All study participants seen at a medical clinic in an area designated for clinical research.
Pre-assignment details
We identified 105 potential subjects. Of these, 42 patients proved to be ineligible, 26 declined invitation to a screening visit, 16 were not able to be scheduled, and 3 were interested but ineligible for the study. Therefore, 18 agreed to be in the study and 17 subjects attended a study screening visit of which 9 were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Vytorin simvastatin, ezetimibe/simvastatin : simvastatin 20 mg daiy ezetimibe/simvastatin 10/20 mg daily placebo for each medication | 4 |
| Zocor simvastatin, ezetimibe/simvastatin : simvastatin 20 mg daiy ezetimibe/simvastatin 10/20 mg daily placebo for each medication | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Zocor | Vytorin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 17.5 years STANDARD_DEVIATION 2.3 | 13.7 years STANDARD_DEVIATION 1.8 | 15.8 years STANDARD_DEVIATION 2.8 |
| Region of Enrollment United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
Primary
Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor.
Change in LDL-c between Zocor and Vytorin treatment in subjects with Type 1 Diabetes measured at baseline to the 6-month study visit.
Time frame: Baseline to 6 months
Population: Recruitment for this study failed to meet target. Due to the small sample size the analyses of these data were primarily descriptive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vytorin (Ezetimibe/Simvastatin) | Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor. | -67 mg/dl | Standard Deviation 47 |
| Zocor (Simvastatin) | Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor. | -6 mg/dl | Standard Deviation 25 |