Type 1 Diabetes
Conditions
Keywords
Type I Diabetes (T1DM), Atorvastatin (Lipitor), Insulin, Pancreas, Beta Cells
Brief summary
The goal of this application is to evaluate the safety and efficacy of atorvastatin as a potential treatment to preserve beta cell function in children and young adults with newly diagnosed type 1 diabetes (T1DM).
Detailed description
Type 1 diabetes is an autoimmune disease that is characterized by destruction of the insulin-producing beta cells of the pancreas. T1DM therapy requires insulin administration, either by multiple daily injections or by insulin pump. However, in many patients, blood sugar control remains suboptimal and complications develop that shorten life expectancy and severely impact quality of life. At the time of diagnosis, most patients still have significant residual beta cell function. Previous research has shown that weakening the immune system's attack on the pancreatic beta cells may help to preserve or potentially increase insulin production. Preliminary studies have shown that members of the statin family of medications, including atorvastatin (Lipitor®), preserve beta cell function in a mouse model of type 1 diabetes. These finding suggest that use of atorvastatin in combination with insulin therapy may delay and potentially reverse the destruction of beta cells in patients who have recently developed type 1 diabetes. Atorvastatin (Lipitor®) is approved for use in adults and children (\>10 years of age) who have elevated blood cholesterol levels. This study will examine whether atorvastatin (Lipitor®) may also help the body preserve insulin production in patients with newly diagnosed (within 8 weeks) type 1 diabetes. Patients will be randomly assigned to take either atorvastatin (Lipitor®) or placebo. Two out of every 3 patients will receive atorvastatin and 1 out of 3 will get placebo. As this is a double-blinded study, neither the care team nor the patient will know if they are actually taking atorvastatin (Lipitor®). Patients who have given consent to participate in the study and pass the required screening tests will take the assigned treatment every day for 12 months. All patients will begin taking 10 mg once daily, the recommended starting dose. After 4 weeks, the dose will be increased to 20 mg. In addition to a high standard of diabetes care and the medication, patients will have blood tests during 7 visits over an 18 month period.
Interventions
DRUGAtorvastatin
Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months
OTHERPlacebo
One out of three subjects will receive a placebo.
Sponsors
FDA Office of Orphan Products Development
Medical University of South Carolina
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Individuals 10-19 years of age (Tanner Stage II or greater), * The presence of one or more serum antibodies to islet cell proteins (anti- glutamic acid decarboxylase \[GAD\], islet antigen 2 or insulin autoantibodies) as assessed in standard practice, * Diagnosis of T1DM within the 8 weeks prior to study entry * Peak stimulated C-peptide level \>0.2pmol/mL following mixed meal tolerance test (MMTT) performed at least 3 weeks after diagnosis, * Females of reproductive potential must not plan on conceiving a child during the treatment program, and agree to use a medically accepted form of contraception
Exclusion criteria
* Subjects currently receiving cyclosporine, fibric acid derivatives, niacin (nicotinic acid), erythromycin, clarythromycin, nefazodone, itraconazole, ketoconazole or protease inhibitors, * Pregnancy or breast-feeding, * Clinical AIDS, AIDS related syndrome (ARS) or known positive HIV serology, * Subjects treated with immunosuppressive therapy in the past 12 months, * Subjects receiving glucocorticoid therapy or therapy other than insulin that is likely to affect glucose homeostasis (such as sulfonylureas, thiazolidinediones, metformin or amylin), * Subjects with other autoimmune diseases, except autoimmune thyroid disease, * Subjects with any illness that might complicate diabetes management or preclude treatment with atorvastatin, * Transplant recipients, * Evidence of liver dysfunction or myopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus | Baseline vs 12-month | The change in C-peptide measurements collected over a 4 hour period (0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after a Mixed Meal Tolerance Test at baseline vs 12 months post-treatment were calculated. The area under the curve for these combined measurements is calculated and the unit of measure is nanogram x minutes / mL. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 1, 2, 3, 4, 5, 6, 7 | Mean daily insulin dose per kg body weight for the 1 week preceding each scheduled study visit. |
| Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 3, 6, 9, 12, and 18 months | — |
| Blood Glucose Control (Number of Participants With Hypoglycemia) | Baseline, Month 12, Month 18 | Blood glucose control as determined from home glucose meter downloads for the 1 week preceding the visit. The number of subjects with hypoglycemic episodes requiring treatment (BG \< 70 mg/dl) |
| % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months | Baseline vs 12 months | The C-peptide AUC measurements are collected over a 2 hour period (with 30 minute intervals) after a Mixed Meal Tolerance Test. The area under the curve from these combined measurements (from 0 to 120 or 0 to 240 minutes) is calculated and the unit of measure is nanogram\*minutes/ml. The change in C-peptide AUC in response to a 2 hour MMTT at baseline vs 12 months were calculated, and efficacy (success) is defined as \< 7.5% reduction. |
| Study Drug Compliance Rate Overall | 12 months treatment | Compliance is defined as \>=80% expected dosage consumed during the visit period. |
| HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline, Week 1, Month 3, Month 6, Month 9, Month 12, | Relationship between atorvastatin's effect on HDL and LDL cholesterol and the preservation of islet cell function. Islet cell preservation defined as: \<7.5% Reduction in C-Pep |
| Number of Episodes of Hypoglycemia Requiring Any Treatment | Baseline, Month 12, Month 18 | number of episodes of hypoglycemia requiring any treatment, defined by the need for treatment with glucagon or third party intervention. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from medical clinics at CHOP from July 2007- January 2010
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Two out of every 3 patients will receive atorvastatin. | 27 |
| Placebo Placebo treatment | 13 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo | Atorvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 26 Participants | 38 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 13.30 years STANDARD_DEVIATION 2.03 | 13.38 years STANDARD_DEVIATION 1.96 | 13.33 years STANDARD_DEVIATION 2.055 |
| Region of Enrollment United States | 13 participants | 27 participants | 40 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 4 Participants | 16 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 27 | 10 / 13 |
| serious Total, serious adverse events | 0 / 27 | 0 / 13 |
Outcome results
Primary
Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus
The change in C-peptide measurements collected over a 4 hour period (0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after a Mixed Meal Tolerance Test at baseline vs 12 months post-treatment were calculated. The area under the curve for these combined measurements is calculated and the unit of measure is nanogram x minutes / mL. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT.
Time frame: Baseline vs 12-month
Population: Participants who completed their 12-month treatment were included in the analysis, in which the change in C-peptide AUC at baseline and 12-months were calculated. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus | 345 nanogram*minutes/ml | Standard Deviation 679 |
| Placebo | Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus | 178 nanogram*minutes/ml | Standard Deviation 308 |
Secondary
Blood Glucose Control (Number of Participants With Hypoglycemia)
Blood glucose control as determined from home glucose meter downloads for the 1 week preceding the visit. The number of subjects with hypoglycemic episodes requiring treatment (BG \< 70 mg/dl)
Time frame: Baseline, Month 12, Month 18
Population: All participants contributing data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atorvastatin | Blood Glucose Control (Number of Participants With Hypoglycemia) | Baseline | 16 Participants |
| Atorvastatin | Blood Glucose Control (Number of Participants With Hypoglycemia) | 12 Month | 16 Participants |
| Atorvastatin | Blood Glucose Control (Number of Participants With Hypoglycemia) | 18 Month | 8 Participants |
| Placebo | Blood Glucose Control (Number of Participants With Hypoglycemia) | Baseline | 7 Participants |
| Placebo | Blood Glucose Control (Number of Participants With Hypoglycemia) | 12 Month | 9 Participants |
| Placebo | Blood Glucose Control (Number of Participants With Hypoglycemia) | 18 Month | 8 Participants |
Secondary
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function
Relationship between atorvastatin's effect on HDL and LDL cholesterol and the preservation of islet cell function. Islet cell preservation defined as: \<7.5% Reduction in C-Pep
Time frame: Baseline, Week 1, Month 3, Month 6, Month 9, Month 12,
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6- HDL Cholesterol (mg/dL) | 48 mg/dl | Standard Deviation 16.07 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1 - LDL Cholesterol (mg/dL) | 68.91 mg/dl | Standard Deviation 16.4 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - HDL Cholesterol (mg/dL) | 47.95 mg/dl | Standard Deviation 14.49 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3 - LDL Cholesterol (mg/dL) | 61 mg/dl | Standard Deviation 20.88 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3- HDL Cholesterol (mg/dL) | 45.05 mg/dl | Standard Deviation 14.49 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline - LDL Cholesterol (mg/dL) | 99.04 mg/dl | Standard Deviation 22.37 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline- HDL Cholesterol (mg/dL) | 47.58 mg/dl | Standard Deviation 16.39 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9 - LDL Cholesterol (mg/dL) | 67.24 mg/dl | Standard Deviation 24.7 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9- HDL Cholesterol (mg/dL) | 49.1 mg/dl | Standard Deviation 14.86 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1- HDL Cholesterol (mg/dL) | 45.43 mg/dl | Standard Deviation 14.33 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - LDL Cholesterol (mg/dL) | 61.52 mg/dl | Standard Deviation 20.04 |
| Atorvastatin | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6 - LDL Cholesterol (mg/dL) | 63.1 mg/dl | Standard Deviation 24.52 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3 - LDL Cholesterol (mg/dL) | 106.25 mg/dl | Standard Deviation 18.44 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline- HDL Cholesterol (mg/dL) | 44.75 mg/dl | Standard Deviation 18 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline - LDL Cholesterol (mg/dL) | 96.13 mg/dl | Standard Deviation 22.99 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1- HDL Cholesterol (mg/dL) | 48.25 mg/dl | Standard Deviation 14.26 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1 - LDL Cholesterol (mg/dL) | 97.63 mg/dl | Standard Deviation 17.9 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3- HDL Cholesterol (mg/dL) | 48.25 mg/dl | Standard Deviation 18.69 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6- HDL Cholesterol (mg/dL) | 50.5 mg/dl | Standard Deviation 20.7 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6 - LDL Cholesterol (mg/dL) | 102.5 mg/dl | Standard Deviation 16.21 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9- HDL Cholesterol (mg/dL) | 45.88 mg/dl | Standard Deviation 12.57 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9 - LDL Cholesterol (mg/dL) | 97 mg/dl | Standard Deviation 4.17 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - HDL Cholesterol (mg/dL) | 45.75 mg/dl | Standard Deviation 16.34 |
| Placebo | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - LDL Cholesterol (mg/dL) | 102.75 mg/dl | Standard Deviation 20.9 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline - LDL Cholesterol (mg/dL) | 83.67 mg/dl | Standard Deviation 25.97 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6 - LDL Cholesterol (mg/dL) | 54 mg/dl | Standard Deviation 7 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9 - LDL Cholesterol (mg/dL) | 65.33 mg/dl | Standard Deviation 28.01 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - HDL Cholesterol (mg/dL) | 57.33 mg/dl | Standard Deviation 14.15 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1- HDL Cholesterol (mg/dL) | 52.33 mg/dl | Standard Deviation 5.69 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline- HDL Cholesterol (mg/dL) | 47.33 mg/dl | Standard Deviation 2.31 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - LDL Cholesterol (mg/dL) | 66 mg/dl | Standard Deviation 23.64 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3- HDL Cholesterol (mg/dL) | 43.33 mg/dl | Standard Deviation 4.04 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9- HDL Cholesterol (mg/dL) | 55.33 mg/dl | Standard Deviation 11.15 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1 - LDL Cholesterol (mg/dL) | 57.67 mg/dl | Standard Deviation 12.06 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3 - LDL Cholesterol (mg/dL) | 48 mg/dl | Standard Deviation 12.17 |
| Atorvastatin YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6- HDL Cholesterol (mg/dL) | 51.67 mg/dl | Standard Deviation 5.51 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3 - LDL Cholesterol (mg/dL) | 91.5 mg/dl | Standard Deviation 20.21 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6- HDL Cholesterol (mg/dL) | 54.75 mg/dl | Standard Deviation 19.47 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - HDL Cholesterol (mg/dL) | 47 mg/dl | Standard Deviation 8.31 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 6 - LDL Cholesterol (mg/dL) | 96.75 mg/dl | Standard Deviation 20.93 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline - LDL Cholesterol (mg/dL) | 99 mg/dl | Standard Deviation 13.04 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9- HDL Cholesterol (mg/dL) | 50 mg/dl | Standard Deviation 21.71 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 12 - LDL Cholesterol (mg/dL) | 96.4 mg/dl | Standard Deviation 6.66 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 9 - LDL Cholesterol (mg/dL) | 90.75 mg/dl | Standard Deviation 8.06 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Baseline- HDL Cholesterol (mg/dL) | 53.2 mg/dl | Standard Deviation 16.39 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1 - LDL Cholesterol (mg/dL) | 86.4 mg/dl | Standard Deviation 12.46 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Month 3- HDL Cholesterol (mg/dL) | 49.25 mg/dl | Standard Deviation 12.31 |
| Placebo YES Islet Cell Preservation | HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function | Week 1- HDL Cholesterol (mg/dL) | 47.2 mg/dl | Standard Deviation 13.88 |
Secondary
Levels of HbA1c at Months 3, 6, 9, 12 and 18
Time frame: 3, 6, 9, 12, and 18 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 6 months | 7.13 percentage of glycated hemoglobin | Standard Deviation 0.9 |
| Atorvastatin | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 12 months | 7.38 percentage of glycated hemoglobin | Standard Deviation 1.19 |
| Atorvastatin | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 9 months | 7.47 percentage of glycated hemoglobin | Standard Deviation 1.44 |
| Atorvastatin | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 18 months | 8.04 percentage of glycated hemoglobin | Standard Deviation 1.82 |
| Atorvastatin | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 3 months | 6.68 percentage of glycated hemoglobin | Standard Deviation 0.95 |
| Placebo | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 18 months | 7.94 percentage of glycated hemoglobin | Standard Deviation 2.62 |
| Placebo | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 3 months | 6.39 percentage of glycated hemoglobin | Standard Deviation 0.95 |
| Placebo | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 6 months | 6.62 percentage of glycated hemoglobin | Standard Deviation 1.22 |
| Placebo | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 9 months | 6.86 percentage of glycated hemoglobin | Standard Deviation 0.91 |
| Placebo | Levels of HbA1c at Months 3, 6, 9, 12 and 18 | 12 months | 7.26 percentage of glycated hemoglobin | Standard Deviation 1.45 |
Secondary
Mean Daily Insulin Dose Per kg Body Weight for 7 Days
Mean daily insulin dose per kg body weight for the 1 week preceding each scheduled study visit.
Time frame: Visit 1, 2, 3, 4, 5, 6, 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 3 | 0.48 units/kg | Standard Deviation 0.21 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 5 | 0.64 units/kg | Standard Deviation 0.22 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 2 | 0.50 units/kg | Standard Deviation 0.25 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 6 | 0.65 units/kg | Standard Deviation 0.24 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 4 | 0.59 units/kg | Standard Deviation 0.21 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 7 | 0.70 units/kg | Standard Deviation 0.35 |
| Atorvastatin | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 1 | 0.53 units/kg | Standard Deviation 0.26 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 7 | 0.71 units/kg | Standard Deviation 0.34 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 1 | 0.62 units/kg | Standard Deviation 0.26 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 2 | 0.52 units/kg | Standard Deviation 0.22 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 3 | 0.50 units/kg | Standard Deviation 0.26 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 4 | 0.47 units/kg | Standard Deviation 0.3 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 5 | 0.59 units/kg | Standard Deviation 0.35 |
| Placebo | Mean Daily Insulin Dose Per kg Body Weight for 7 Days | Visit 6 | 0.64 units/kg | Standard Deviation 0.36 |
Secondary
Number of Episodes of Hypoglycemia Requiring Any Treatment
number of episodes of hypoglycemia requiring any treatment, defined by the need for treatment with glucagon or third party intervention.
Time frame: Baseline, Month 12, Month 18
Population: All subjects contributing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atorvastatin | Number of Episodes of Hypoglycemia Requiring Any Treatment | Baseline | 4.13 episodes | Standard Deviation 3.95 |
| Atorvastatin | Number of Episodes of Hypoglycemia Requiring Any Treatment | Month 12 | 3.44 episodes | Standard Deviation 3.01 |
| Atorvastatin | Number of Episodes of Hypoglycemia Requiring Any Treatment | Month 18 | 2.75 episodes | Standard Deviation 3.65 |
| Placebo | Number of Episodes of Hypoglycemia Requiring Any Treatment | Baseline | 2.86 episodes | Standard Deviation 3.98 |
| Placebo | Number of Episodes of Hypoglycemia Requiring Any Treatment | Month 12 | 2.44 episodes | Standard Deviation 2.51 |
| Placebo | Number of Episodes of Hypoglycemia Requiring Any Treatment | Month 18 | 2.5 episodes | Standard Deviation 2.2 |
Secondary
Study Drug Compliance Rate Overall
Compliance is defined as \>=80% expected dosage consumed during the visit period.
Time frame: 12 months treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin | Study Drug Compliance Rate Overall | 85.1 % of compliant participants |
| Placebo | Study Drug Compliance Rate Overall | 76.9 % of compliant participants |
Secondary
% Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months
The C-peptide AUC measurements are collected over a 2 hour period (with 30 minute intervals) after a Mixed Meal Tolerance Test. The area under the curve from these combined measurements (from 0 to 120 or 0 to 240 minutes) is calculated and the unit of measure is nanogram\*minutes/ml. The change in C-peptide AUC in response to a 2 hour MMTT at baseline vs 12 months were calculated, and efficacy (success) is defined as \< 7.5% reduction.
Time frame: Baseline vs 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atorvastatin | % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months | 14.8 % of participants with efficacy |
| Placebo | % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months | 38.4 % of participants with efficacy |