Rosiglitazone And Fenofibrate Additive Effects on Lipids (RAFAEL) - Full Text View

Sponsors and Collaborators:	Brooke Army Medical Center GlaxoSmithKline
Information provided by:	Brooke Army Medical Center
ClinicalTrials.gov Identifier:	NCT00819910

Purpose

The design of the study will be randomized, double blind trial, which will examine the effects of Rosiglitazone on the fasting TG, HDL, HDL particle size, LDL, LDL particle size, and plasma concentrations of apolipoproteins A-I, A-II, and C-III, function compared to Fenofibrate and placebo. This study will also assess the synergistic effect of Rosiglitazone and Fenofibrate on the same parameters. Data from this study will help clarify whether Rosiglitazone favorably impacts plasma lipid and lipoprotein concentrations through improving insulin sensitivity and glycemic control, or by directly influencing the synthesis of the apolipoproteins that are responsible for VLDL and HDL metabolism.

Condition	Intervention	Phase
Type 4 Hyperlipidemia Normoglycemia	Drug: Rosiglitazone Drug: Placebo (Rosiglitazone) Drug: Placebo (Fenofibrate) Drug: Fenofibrate	Phase IV

Drug Information available for: Procetofen Lipids Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Rosiglitazone And Fenofibrate Additive Effects on Lipids (RAFAEL)

Further study details as provided by Brooke Army Medical Center:

Primary Outcome Measures:

The primary end-point with respect to efficacy is percent change in TG levels with Rosiglitazone therapy as compared to placebo. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The primary safety end-point is the incidence of transaminitis more than three times the upper limit of normal. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Percent change in HDL levels with Rosiglitazone therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change in LDL levels with Rosiglitazone therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change in Apo AI, Apo AII and Apo CIII levels with Rosiglitazone therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
percent change in HDL particle size with Rosiglitazone therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
percent change in LDL particle size with Rosiglitazone therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change in HDL levels with Rosiglitazone/Fenofibrate combination therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change in LDL levels with Rosiglitazone/Fenofibrate combination therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change in Apo AI, Apo AII and Apo CIII levels with Rosiglitazone/Fenofibrate combination therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
percent change in HDL particle size with Rosiglitazone/Fenofibrate combination therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
percent change in LDL particle size with Rosiglitazone/Fenofibrate combination therapy as compared to placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	September 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Double placebo of Fenofibrate and Rosiglitazone for 12 weeks	Drug: Placebo (Rosiglitazone) Drug: Placebo (Fenofibrate)
2: Active Comparator Fenofibrate 145 mg daily for 12 weeks Placebo (rosiglitazone) for 12 weeks	Drug: Placebo (Rosiglitazone) Drug: Fenofibrate Fenofibrate 145 mg daily for 12 weeks
3: Experimental Rosiglitazone 8mg daily for 12 weeks Fenofibrate (placebo) for 12 weeks	Drug: Rosiglitazone Rosiglitazone 8mg daily for 12 weeks Drug: Placebo (Fenofibrate)
4: Experimental Rosiglitazone 8mg and Fenofibrate 145 mg daily for 12 weeks	Drug: Rosiglitazone Rosiglitazone 8mg daily for 12 weeks Drug: Fenofibrate Fenofibrate 145 mg daily for 12 weeks

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria:

Fasting plasma glucose <100 mg/dl
Fasting LDL <160 mg/dl and Triglyceride <400 mg/dl.

Exclusion criteria:

Congestive heart failure
Evidence of renal impairment (serum creatinine> 1.4mg/dL)
Liver disease (ALT and/or AST above the upper level of normal)
Known diabetes mellitus or impaired fasting glucose (fasting glucose ≥ 100mg/dL)
LDL of ≥160mg/dL and/or triglycerides of ≥400mg/dL
Pregnant or breast feeding women
Prior history of an acute coronary syndrome, myocardial infarction or revascularization procedures in the past
Life-threatening disease with a survival prognosis <3 years
Inability to take rosiglitazone and/or fenofibrate
Already on statin therapy or have been on statin therapy in the last 3 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819910

Contacts

Contact: Ahmad M Slim, MD	210-916-4717	Ahmad.slim@us.army.mil
Contact: Dorette PearceMoore, ANP	210-916-4717	Dorette.pearcemoore@amedd.army.mil

Locations

United States, Texas
Brooke Army Medical Center	Recruiting
San Antonio, Texas, United States, 78234
Contact: Ahmad m slim, MD 210-916-4717 ahmad.slim@us.army.mil
Contact: Dorette Pearcemoore, ANP 210-916-4717 dorrette.pearcemoore@amedd.army.mil

Sponsors and Collaborators

Brooke Army Medical Center

GlaxoSmithKline

Investigators

Principal Investigator:	Ahmad m slim, MD	Brooke Army Medical Center
Study Chair:	Laudino Castillo-rojas, MD	Brooke Army Medical Center
Study Chair:	Paul Garrett, MD	Brooke Army Medical Center

More Information

Publications:

1. American Diabetes association. Standards of medical care for patients with Diabetes Mellitus. Diabetes Care 1997 ;20 : Suppl 1 :55-513.

O'Rourke CM, Davis JA, Saltiel AR, Cornicelli JA. Metabolic effects of troglitazone in the Goto-Kakizaki rat, a non-obese and normolipidemic rodent model of non-insulin-dependent diabetes mellitus. Metabolism. 1997 Feb;46(2):192-8.

Lee MK, Miles PD, Khoursheed M, Gao KM, Moossa AR, Olefsky JM. Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes. 1994 Dec;43(12):1435-9.

Ciaraldi TP, Gilmore A, Olefsky JM, Goldberg M, Heidenreich KA. In vitro studies on the action of CS-045, a new antidiabetic agent. Metabolism. 1990 Oct;39(10):1056-62.

5. Troglitazone study group. The metabolic effects of troglitazone in non-insulin dependent diabetes. Diabetes 197; 46:Suppl 1:149A.

Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med. 1994 Nov 3;331(18):1188-93.

Chu NV, Kong AP, Kim DD, Armstrong D, Baxi S, Deutsch R, Caulfield M, Mudaliar SR, Reitz R, Henry RR, Reaven PD. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 2002 Mar;25(3):542-9. Erratum in: Diabetes Care 2002 May;25(5):947.

Coresh J, Kwiterovich PO Jr. Small, dense low-density lipoprotein particles and coronary heart disease risk: A clear association with uncertain implications. JAMA. 1996 Sep 18;276(11):914-5. No abstract available.

Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, Hennekens CH. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA. 1996 Sep 18;276(11):882-8.

Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996 Sep 18;276(11):875-81.

Dunn, F.L. Hyperlipidemia and diabetes. Med. Clin. N. Amer. 1982 ; 66 :1347-1369.

Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 1996 May;37(5):907-25. Review.

Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10;98(19):2088-93. Review.

Bähr M, Spelleken M, Bock M, von Holtey M, Kiehn R, Eckel J. Acute and chronic effects of troglitazone (CS-045) on isolated rat ventricular cardiomyocytes. Diabetologia. 1996 Jul;39(7):766-74.

Ciaraldi TP, Huber-Knudsen K, Hickman M, Olefsky JM. Regulation of glucose transport in cultured muscle cells by novel hypoglycemic agents. Metabolism. 1995 Aug;44(8):976-81.

Saltiel, A.R., Olefsky, J.M. Thiazolidinedione is a high affinity ligand of peroxisome proliferator-activated receptor. J. Biol. Chem. 1996 ;270 :12953-12956.

Lefebvre AM, Peinado-Onsurbe J, Leitersdorf I, Briggs MR, Paterniti JR, Fruchart JC, Fievet C, Auwerx J, Staels B. Regulation of lipoprotein metabolism by thiazolidinediones occurs through a distinct but complementary mechanism relative to fibrates. Arterioscler Thromb Vasc Biol. 1997 Sep;17(9):1756-64.

Responsible Party:	Brooke Army Medical Center ( Ahmad Slim, MD, FACP, MAJOR, MC )
Study ID Numbers:	C.2007.122
Study First Received:	January 8, 2009
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00819910 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Brooke Army Medical Center:

Type 4 hyperlipidemia
Rosiglitazone
Fenofibrate

Study placed in the following topic categories:

Antimetabolites
Hypoglycemic Agents
Metabolic Diseases
Hyperlipidemias
Antilipemic Agents

Procetofen
Rosiglitazone
Metabolic Disorder
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites
Hyperlipidemias
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Physiological Effects of Drugs
Procetofen

Pharmacologic Actions
Hypoglycemic Agents
Therapeutic Uses
Rosiglitazone
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 06, 2009