DIATOR-Diabetes Intervention With Atorvastatin

DIATOR - Diabetes Intervention With Atorvastatin. A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Investigate the Effect of Atorvastatin on Residual Beta-cell Function and Glycemic Control in Patients With Newly Diagnosed Type 1 Diabetes Mellitus

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.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: atorvastatin matching placebo; Drug: Atorvastatin

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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bad Mergentheim, Germany, 97980
    • Diabetes-Zentrum Mergentheim
  • Berlin, Germany, 14165
    • Helios Klinikum Emil Von Behring
  • Berlin, Germany, 14089
    • Gemeinschaftskrankenhaus Havelhöhe
  • Bestwig-Ramsbeck, Germany, 59909
    • Praxis Dr. Friedhelm Schmitten
  • Düsseldorf, Germany, 40221
    • DDZ Deutsches Diabetes Zentrum
  • Heidelberg, Germany, 69115
    • St. Josefs Krankenhaus
  • Köln, Germany, 50968
    • St. Antonius Krankenhaus, Med. Klinik
  • Leipzig, Germany, 04103
    • Praxisklinik Leipzig
  • Leverkusen, Germany, 51373
    • Praxis Dr. Gerhard Willms
  • Marl, Germany, 45770
    • Praxis Dr. Heinz-Georg Ley
  • Münster, Germany, 48145
    • Diabetologische Schwerpunktpraxis, Angiologie
  • Würzburg, Germany, 97070
    • Praxis Dr. Werner Stürmer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: atorvastatin matching placebo	Drug: atorvastatin 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)
Experimental: atorvastatin; 40 mg atorvastatin for 4 weeks (run-in period), then 80 mg atorvastatin, total treatment period was 18 months	Drug: Atorvastatin; 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); Other Names: Sortis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-peptide after a liquid mixed meal stimulation	at randomization, after 12 months, and after 18 months of treatment

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Profil Institut für Stoffwechselforschung GmbH
• Collaborators: Pfizer
• Investigators: Principal Investigator: Stefan Martin, MD, DDZ Deutsches Diabetes Zentrum, Düsseldorf, Germany

Publications and helpful links

General Publications

• Kolb H, Luckemeyer K, Heise T, Herder C, Schloot NC, Koenig W, Heinemann L, Martin S; DIATOR Study Group. The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial). PLoS One. 2013 Aug 26;8(8):e72440. doi: 10.1371/journal.pone.0072440. eCollection 2013.
• Strom A, Kolb H, Martin S, Herder C, Simon MC, Koenig W, Heise T, Heinemann L, Roden M, Schloot NC; DIATOR Study Group. Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial). PLoS One. 2012;7(3):e33108. doi: 10.1371/journal.pone.0033108. Epub 2012 Mar 20.
• Martin S, Herder C, Schloot NC, Koenig W, Heise T, Heinemann L, Kolb H; DIATOR Study Group. Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial. PLoS One. 2011 Mar 11;6(3):e17554. doi: 10.1371/journal.pone.0017554.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 9, 2009
• First Posted (Estimate): September 10, 2009

Study Record Updates

• Last Update Posted (Actual): June 19, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: type 1 diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 33/0136-Diator