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Rosiglitazone And Fenofibrate Additive Effects on Lipids (RAFAEL)
This study has been completed.

First Received on January 8, 2009.   Last Updated on July 7, 2010   History of Changes
Sponsor: Brooke Army Medical Center
Collaborator: 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 triglycerides (TG), high-density lipoprotein (HDL), HDL particle size, low-density lipoprotein (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 very-low-density lipoprotein (VLDL) and HDL metabolism.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Rosiglitazone And Fenofibrate Additive Effects on Lipids (RAFAEL)

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines
Drug Information available for: Procetofen Lipids Rosiglitazone Rosiglitazone Maleate
U.S. FDA Resources

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
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Double placebo of Fenofibrate and Rosiglitazone for 12 weeks
 Drug: Placebo (Rosiglitazone) Drug: Placebo (Fenofibrate)
Active Comparator: 2
Fenofibrate 145 mg daily for 12 weeks Placebo (rosiglitazone) for 12 weeks
 Drug: Placebo (Rosiglitazone) Drug: Fenofibrate
Fenofibrate 145 mg daily for 12 weeks
Experimental: 3
Rosiglitazone 8mg daily for 12 weeks Fenofibrate (placebo) for 12 weeks
 Drug: Rosiglitazone
Rosiglitazone 8mg daily for 12 weeks
Drug: Placebo (Fenofibrate)
Experimental: 4
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:

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

Exclusion criteria:

  1. Congestive heart failure
  2. Evidence of renal impairment (serum creatinine> 1.4mg/dL)
  3. Liver disease (ALT and/or AST above the upper level of normal)
  4. Known diabetes mellitus or impaired fasting glucose (fasting glucose ≥ 100mg/dL)
  5. LDL of ≥160mg/dL and/or triglycerides of ≥400mg/dL
  6. Pregnant or breast feeding women
  7. Prior history of an acute coronary syndrome, myocardial infarction or revascularization procedures in the past
  8. Life-threatening disease with a survival prognosis <3 years
  9. Inability to take rosiglitazone and/or fenofibrate
  10. 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

Locations
United States, Texas
Brooke Army Medical Center
San Antonio, Texas, United States, 78234
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 Director: Jennifer N Slim, DO 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.
11. Weinber, R.B. Lipoprotein metabolism: hormone regulation. Hosp. Prac 1987 :June' 15 :125-145.
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: Ahmad Slim, MD, FACP, MAJOR, MC, Brooke Army Medical Center
ClinicalTrials.gov Identifier: NCT00819910     History of Changes
Other Study ID Numbers: C.2007.122
Study First Received: January 8, 2009
Last Updated: July 7, 2010
Health Authority: United States: Federal Government

Keywords provided by Brooke Army Medical Center:
Type 4 hyperlipidemia
Rosiglitazone
Fenofibrate

Additional relevant MeSH terms:
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Fenofibrate
Rosiglitazone
Hypolipidemic Agents
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012



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