Clinical trial NCT00974740: DIATOR-Diabetes Intervention With Atorvastatin
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Type 1 Diabetes
Keywords: type 1 diabetes
Lead sponsor: Profil Institut für Stoffwechselforschung GmbH
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2009-09-10
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: C-peptide after a liquid mixed meal stimulation
timeFrame: at randomization, after 12 months, and after 18 months of treatment
Secondary outcomes:
measure: HbA1c
timeFrame: at randomization, after 6, 12, and 18 months of treatment
measure: insulin dose
timeFrame: at randomization, and after 3, 6, 12, and 18 months of treatment
measure: adverse events
timeFrame: at randomization, and after 3, 6, 12, and 18 months of treatment
measure: serum lipids
timeFrame: at randomization, and after 3, 6, 12, and 18 months of treatment
measure: plasma CRP
timeFrame: at randomization, and after 3, 12, and 18 months of treatment
Other outcomes:
Locations:
city: Bad Mergentheim
country: Germany
facility: Diabetes-Zentrum Mergentheim
city: Berlin
country: Germany
facility: Gemeinschaftskrankenhaus Havelhöhe
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring
city: Bestwig-Ramsbeck
country: Germany
facility: Praxis Dr. Friedhelm Schmitten
city: Düsseldorf
country: Germany
facility: DDZ Deutsches Diabetes Zentrum
city: Heidelberg
country: Germany
facility: St. Josefs Krankenhaus
city: Köln
country: Germany
facility: St. Antonius Krankenhaus, Med. Klinik
city: Leipzig
country: Germany
facility: Praxisklinik Leipzig
city: Leverkusen
country: Germany
facility: Praxis Dr. Gerhard Willms
city: Marl
country: Germany
facility: Praxis Dr. Heinz-Georg Ley
city: Münster
country: Germany
facility: Diabetologische Schwerpunktpraxis, Angiologie
city: Würzburg
country: Germany
facility: Praxis Dr. Werner Stürmer
Study officials:
affiliation: DDZ Deutsches Diabetes Zentrum, Düsseldorf, Germany
name: Stefan Martin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.