Clinical trial NCT00529191: Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM)
Official title: Phase II, Double Blind, Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Atorvastatin in Subjects With Newly Diagnosed Type 1 Diabetes Mellitus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type I Diabetes (T1DM)
Atorvastatin (Lipitor)
Insulin
Pancreas
Beta Cells
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
name: Medical University of South Carolina
First posted: 2007-09-14
Enrollment: 40
Sex: ALL
Minimum age (years): 10
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline vs 12-month
Secondary outcomes:
measure: % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months
timeFrame: Baseline vs 12 months
measure: Mean Daily Insulin Dose Per kg Body Weight for 7 Days
timeFrame: Visit 1, 2, 3, 4, 5, 6, 7
measure: Levels of HbA1c at Months 3, 6, 9, 12 and 18
timeFrame: 3, 6, 9, 12, and 18 months
measure: Blood Glucose Control (Number of Participants With Hypoglycemia)
timeFrame: Baseline, Month 12, Month 18
measure: Number of Episodes of Hypoglycemia Requiring Any Treatment
timeFrame: Baseline, Month 12, Month 18
measure: Study Drug Compliance Rate Overall
timeFrame: 12 months treatment
measure: HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function
timeFrame: Baseline, Week 1, Month 3, Month 6, Month 9, Month 12,
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Diabetes Center for Children & Clinical Translational Research Center
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Steven M Willi, M.D
role: PRINCIPAL_INVESTIGATOR
References: