Diabetes and Combined Lipid Therapy Regimen (DIACOR) Study
|First Received Date ICMJE||March 30, 2006|
|Last Updated Date||August 20, 2008|
|Start Date ICMJE||August 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||percent of patients achieving study goal oftriglycerides <200 mg/dL|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00309712 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Percent of patients achieving all study goals: LDL-C < 100 mg/dL, HDL-C:40 mg/dL, Triglycerides <200 mg/dL and the Percent of patients achieving non-HDL cholesterol <130 mg/dL|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Diabetes and Combined Lipid Therapy Regimen (DIACOR) Study|
|Official Title ICMJE||Diabetes and Combined Lipid Therapy Regimen (DIACOR) Study: A Randomized, Double-Blind Study of Simvastatin, Fenofibrate, and Combined Fenofibrate and Simvastatin in Patients With Controlled Type II Diabetics Without Evidence of Coronary Disease|
The primary study hypothesis of this study is to determine whether there is a greater percentage of patients achieving a triglyceride level of <200 mg/dL with the combination of simvastatin 20 mg and fenofibrate 160mg than with either simvastatin 20 mg monotherapy or fenofibrate 160mg monotherapy.
Diabetes is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia with hypertriglyceridemia,low high-density lipoprotein (HDL), and modestly elevated low-density lipoprotein (LDL). Both HMG-CoA reductase inhibitors (statins) and fibrates improve lipoprotein metabolism and decrease coronary disease risk. Statins and fibrates affect different aspects of lipoprotein metabolism and each improve lipid metabolism complimentarily. Statins lower total cholesterol and LDL while fibrates decrease triglyceride concentrations and elevateHDL cholesterol. Since individual lipid parameters have been shown to be independent cardiovascular risk factors, it is especially important to target all lipid parameters to levels outlined in treatment guidelines.
The National Cholesterol Education Program Adult Treatment Panel ill (NCEP ill) guidelines have set target therapeutic levels for coronary heart disease (CHD) and CHD risk equivalents (including diabetes).Many patients, however, are not able to achieve optimal levels with a single lipid-controlling agent.
This is particularly evident among diabetics, who often have multiple dyslipidemias and are less likely to achieve effective lipid control.
Several small clinical trials have demonstrated that fibrate and statin dual therapy combine the specific effects of the two drugs by significantlyreducing total and LDL cholesterol while increasing HDL cholesterol, though problems are associated. Previous studies, conducted mainly with a gemfibrozil/cerivastatin combination, showed an increased incidence of side effects (myopathy, hepatotoxicity) and high cost. This problem was again addressed in a small study of74 patients randomized to combined or alternate-day simvastatin and fenofibrate therapy. Surprisingly, in this study, no cases of myopathy were reported, even among patients receiving combined simvastatin and fenofibrate therapy.
The Lipids in Diabetes Study (LDSH Study) examined the fenofibrate and cerivastatin combination in a large-scale trial of 4,000 patients. This study was stopped early because study treatment included cerivastatin, which was withdrawn from the United States market in 2001. Consequently, the results' utility will be limited in the United States.
Additional studies evaluating lipid therapies capable of meeting more aggressive treatment guidelines outlined in NCEP ill, especially among diabetic patients, are required. We propose a twelve-month study of simvastatin, micronized fenofibrate, and combination therapy among patients with controlled Type 2 diabetes mellitus. The primary objectives ofthis study will be to assess the safety and efficacy of combined micronized fenofibrate and simvastatin therapy versus micronized fenofibrate or simvastatin monotherapy. Secondary objectives will include evaluation of combined micronized fenofibrate and simvastatin therapy versus micronized fenofibrate or simvastatin monotherapy on novel lipid parameters and serological markers associated with significantly increased cardiovascular risk. The benefits of the study will be numerous. First, we will be able to detennine the efficacy of each treatment arm in achieving the more aggressive lipid level targets outlined in NCEP ill. Second, this trial, unlike previous studies, will assess the safety and efficacy of each treatment arm specifically among diabetic patients. Third, the length of therapy will allow adequate, yet efficient, evaluation of the tertiary endpoints, which include novel risk factors not previously assessed with combination therapy.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Study Arm (s)||Not Provided|
|Publications *||Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, Wolfert RL, Pearson RR, Yannicelli HD, Anderson JL. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol. 2006 Jul 18;48(2):396-401. Epub 2006 May 24.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
j. The patient understands the requirements of the study, and voluntarily agrees to participate in the study and provides informed consent
Formula for Males:
CrCI= (140-age [years])x (body weight [kg]) (72) x (serum Cr [mg/elL])
Formula for Females:
CrCI=(140-age [years]) x (body weight [kg]) x 0.85 (72) x (serum Cr [mg/dL]) g. Active liver disease including viral hepatitis (hepatitis B or C) as determined by positive antibodies to core and surface antigen for hepatitis B, and positive antibodies for hepatitis C h. Uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg i. Proteinuria as defined by >0.5 mg albumin per mg creatinine (if dipstick> 1+) or history of nephrotic syndrome j. Secondary hypercholesteremia due to hypothyroidism (TSH >6~U/mL) or nephrotic syndrome; Patients with a history of hypothyroidism, who are on a stable dose of thyroxine with normalized plasma thyroxine and TSH may be included k. Diagnosis of homozygous familial hypercholesteremia, or Types I or V hyperlipidemia 1. The concomitant use of cyclosporine; systemic itraconazole or ketoconazole, erythromycin or clarithromycin, nefazadone, or HIV protease inhibitors are excluded. The concomitant use of systemic (pO or IV) glucocorticoids, and verapamil (other calcium channel blockers are acceptable), or the consumption oflarge amounts of grapefruitjuice (> 1 quart) are excluded. m. Known hypersensitivity to any component of HMG-CoA reductase inhibitors or fibrates including history of elevated liver or muscle function tests, jaundice, or hepatotoxicity or myopathy associated with these treatments n. History of partial ileal bypass o. Treatment with any other investigational drug within the previous 30 days Currently using illicit drugs; history of drug or alcohol abuse within the past 5 years Type 1 diabetes mellitus, hyperlipidemicpancreatitis or known presence of cholelithiasis (gallstones); Any therapy or condition that would pose a risk to the patient or make it difficult for the patient to comply with requirements of the study s. Participation in any other studies involving investigational or marketed products within 30 prior to entryin the study. .
1. Pregnantand/orlactatingwomen,andwomenof childbearingpotentialnot usingacceptablemeansof contraception.Womenof childbearingpotentialmustbe usingadequatemeasuresof contraception(as determinedby the investigator)to avoidpregnancyandshouldbe highlyunlikelyto conceiveduringthe study period. Womenof childbearingpotentialmusthavea negativepregnancytest at the timeof initialscreening.
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00309712|
|Other Study ID Numbers ICMJE||128-009|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Intermountain Health Care, Inc.|
|Information Provided By||Intermountain Health Care, Inc.|
|Verification Date||August 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP