Type 1 Diabetes
Conditions
Keywords
type 1 diabetes
Brief summary
Clinical studies have shown that immunomodulators (like Anti-CD3 antibodies) have effects on beta-cell-preservation. The lipid-lowering agent atorvastatin is also a potent immunomodulator. In this study the effects of 80 mg atorvastatin per day on preservation of beta-cell function in recent onset type 1 diabetes were studied, as determined by stimulated C-peptide levels.
Detailed description
The objectives of this study were as follows: * To assess the effect of atorvastatin on pancreatic beta-cell function as measured by C-peptide after a liquid mixed meal stimulation in patients with newly diagnosed type 1 diabetes, * To assess the effect on metabolic control as measured by HbA1c and insulin requirements, * To assess safety and tolerability of atorvastatin in subjects with newly diagnosed type 1 diabetes, * To assess the effect on risk factors of diabetic complications as indicated by changes in lipids and CRP, and * To assess the effect on systemic immune abnormalities as measured by effects on beta-cell autoantibodies, blood cytokines and chemokines on protein and transcriptional level. Study duration: 18 months
Interventions
DRUGAtorvastatin
atorvastatin 40 mg (tablet for oral intake) once daily in the evening for 4 weeks, thereafter 80 mg for the remaining treatment period (total treatment period 18 months)
DRUGatorvastatin matching placebo
atorvastatin matching placebo tablets once daily in the evening, corresponding to 40 mg atorvastatin for the first 4 weeks (run-in period), and corresponding to 80 mg atorvastatin thereafter (total treatment period 18 months)
Sponsors
Pfizer
Profil Institut für Stoffwechselforschung GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* Insulin treated patients with a newly diagnosed type 1 diabetes mellitus as defined by the ADA criteria at least two weeks but not later than 3 months after start of insulin treatment * Age 18 to 39 years, inclusive * Male patient or female patient using adequate contraceptive methods * Tested positive for at least one of the three islet autoantibodies GAD65, IA2 or ICA
Exclusion criteria
* History of a malignancy * Presence of a clinically significant hepatic or renal disease, as indicated, but not limited to a serum creatinine elevated more than ten percent above the upper limit of normal, elevation of AST or ALT more than 3 times the upper limit of normal * Any other acute or chronic condition that may affect the patient's response to treatment or might be associated with an increased risk for the patient to participate, as judged by the investigator * Current use of anti-inflammatory or immunomodulatory drugs, antihypertensive, lipid-lowering, or antidiabetic drugs other than insulin * Pregnant or nursing women or women intending to become pregnant * Known or suspected allergy to atorvastatin or any component of thr trial product * Known myopathy, myalgia or myositis with a serum-CPK above 3 times the upper limit of normal * Patients who had a severe blood loss (\>= 400 mL, e.g. blood donation) within 2 months prior to visit 2 * Any significant laboratory abnormality * A serum LDL-cholesterol above 150 mg/dL at time of screening * Unwillingness to comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| C-peptide after a liquid mixed meal stimulation | at randomization, after 12 months, and after 18 months of treatment |
Secondary
| Measure | Time frame |
|---|---|
| HbA1c | at randomization, after 6, 12, and 18 months of treatment |
| insulin dose | at randomization, and after 3, 6, 12, and 18 months of treatment |
| adverse events | at randomization, and after 3, 6, 12, and 18 months of treatment |
| serum lipids | at randomization, and after 3, 6, 12, and 18 months of treatment |
| plasma CRP | at randomization, and after 3, 12, and 18 months of treatment |
Countries
Germany
Outcome results
None listed