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Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM) (TIDM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00529191
Recruitment Status : Completed
First Posted : September 14, 2007
Results First Posted : March 8, 2013
Last Update Posted : March 13, 2017
FDA Office of Orphan Products Development
Medical University of South Carolina
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Tracking Information
First Submitted Date  ICMJE September 13, 2007
First Posted Date  ICMJE September 14, 2007
Results First Submitted Date  ICMJE December 20, 2012
Results First Posted Date  ICMJE March 8, 2013
Last Update Posted Date March 13, 2017
Study Start Date  ICMJE July 2007
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2007)
4-hour C-peptide AUC in response to MMTT. [ Time Frame: baseline vs 12 months ]
Change History Complete list of historical versions of study NCT00529191 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
  • % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months [ Time Frame: 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.
  • Mean Daily Insulin Dose Per kg Body Weight for 7 Days [ Time Frame: 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 [ Time Frame: 3, 6, 9, 12, and 18 months ]
  • Blood Glucose Control (Number of Participants With Hypoglycemia) [ Time Frame: 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)
  • Number of Episodes of Hypoglycemia Requiring Any Treatment [ Time Frame: 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.
  • Study Drug Compliance Rate Overall [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2007)
•2-hour and 4-hour C-peptide AUC. •Hemoglobin A1c levels •Mean daily insulin dose per kg body weight for 1 week •Mean blood glucose (BG), number of preprandial BG > 160 mg/dL or < 70 mg/dL, and postprandial BG >200 mg/dL [ Time Frame: baseline, 1,3,6,9,12,18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM)
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE
  • Drug: Atorvastatin
    Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months
    Other Name: Lipitor
  • Other: Placebo
    One out of three subjects will receive a placebo.
Study Arms  ICMJE
  • Experimental: Atorvastatin
    Two out of every three patients will receive atorvastatin.
    Intervention: Drug: Atorvastatin
  • Placebo Comparator: Placebo
    One out of three subjects will receive a placebo.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 7, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2007)
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00529191
Other Study ID Numbers  ICMJE 2006-5-4824
R01FD003340 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share these data, except in aggregate.
Responsible Party Children's Hospital of Philadelphia
Study Sponsor  ICMJE Children's Hospital of Philadelphia
Collaborators  ICMJE
  • FDA Office of Orphan Products Development
  • Medical University of South Carolina
Investigators  ICMJE
Principal Investigator: Steven M Willi, M.D Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP