NCT01156597

Brief Summary

Metabolic defects contributing to the development of type 2 diabetes (T2D) are relative insulin insufficiency and insulin resistance that are associated with a cluster of abnormalities that increase the risk for cardiovascular disease including dyslipidemia, inflammation, hemodynamic changes and endothelial dysfunction. The dyslipidemia associated with T2D is characterized by elevated triglycerides and decreased high-density lipoprotein-cholesterol (HDL). The ability of the insulin sensitizing agent pioglitazone (ACTOS®) , to improve hyperglycemia in subjects with T2D is now well established. Pioglitazone functions as a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonists and this class of drugs have demonstrated several other potential benefits, beyond glucose homeostasis. Specifically pioglitazone can improve diabetic dyslipidemia by increasing HDL cholesterol and lowing triglycerides. A potential beneficial effect on reverse cholesterol transport may be mediated by the increased HDL levels. This proposal aims to examine the effect of PPAR-γ activation by PIO on various aspects of reverse cholesterol transport by testing the hypothesis that PIO treatment affects key steps in the reverse cholesterol transport pathway either directly, through induction of protein expression, or indirectly, by altering HDL structure and composition leading to increase cholesterol flux through this pathway.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for phase_3 type-2-diabetes-mellitus

Timeline
Completed

Started Apr 2008

Longer than P75 for phase_3 type-2-diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2008

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

July 2, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 5, 2010

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2010

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

November 11, 2014

Completed
Last Updated

November 21, 2014

Status Verified

November 1, 2014

Enrollment Period

2.4 years

First QC Date

July 2, 2010

Results QC Date

April 18, 2014

Last Update Submit

November 11, 2014

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetesdyslipidemiapioglitazoneHDL-CholesterolReverse cholesterol transport

Outcome Measures

Primary Outcomes (1)

  • Increased HDL-Cholesterol and Decreased Triglycerides

    The primary endpoint will be increased high density lipoprotein cholesterol and decreased triglycerides measured as the difference after 12 or 24 weeks of treatment from baseline levels. The data are expressed as the percent change from the baseline value and calculated using he equation: * Change=\[100%\*(Endpoint value - Baseline Value)/Baseline Value\]

    24 weeks

Secondary Outcomes (2)

  • HDL Apolipoprotein Levels at Study End-point

    24 weeks

  • Cholesterol Efflux Capacity of HDL

    24 weeks

Study Arms (2)

Pioglitazone Group

ACTIVE COMPARATOR

This is a baseline versus treatment study comparing subjects on pioglitazone to a matched group of subjects treated with either metformin or sulfonylurea with the intent of controlling blood sugar to a comparable level

Drug: pioglitazone

Comparator Group

NO INTERVENTION

This group of subjects will be maintained on standard treatment with either metformin or sulfonylurea with the intent of controlling blood sugar to a comparable level as group treated with pioglitazone.

Interventions

pioglitazoneDRUG

30 mg daily for three weeks increase to 45 mg daily for 21 more weeks

Also known as: ACTOS
Pioglitazone Group

Eligibility Criteria

Age35 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 2 diabetes, men and women, WHO criteria, aged 35-70 years
  • HbA1c 7.5-10.0%
  • BMI 26-39 Kg/m2
  • Either receiving dietary therapy only or monotherapy with either sulfonylurea or metformin
  • Already on statin therapy

You may not qualify if:

  • Cardiovascular disease
  • Renal disease
  • Other systemic disease
  • Abnormal liver function tests (ALT or AST\>1.5 X ULN)
  • Uncontrolled hypertension (BP \>160/110)
  • Triglyceride levels \>400 mg/dl
  • Lipid modifying drugs; fibrates, ezetimibe, niacin, bile sequestrants, but not statins (see below),
  • Estrogen treatment or thyroid disease
  • Psychiatric condition or substance abuse

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Diabetes Research Institute

Miami, Florida, 33136, United States

Location

Related Publications (5)

  • Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: The glitazones or insulin sensitizers. Annu Rev Med. 2001;52:239-57. doi: 10.1146/annurev.med.52.1.239.

    PMID: 11160777BACKGROUND

  • Campbell IW. Long-term glycaemic control with pioglitazone in patients with type 2 diabetes. Int J Clin Pract. 2004 Feb;58(2):192-200. doi: 10.1111/j.1368-5031.2004.0108.x.

    PMID: 15055868BACKGROUND

  • Olansky L, Marchetti A, Lau H. Multicenter retrospective assessment of thiazolidinedione monotherapy and combination therapy in patients with type 2 diabetes: comparative subgroup analyses of glycemic control and blood lipid levels. Clin Ther. 2003;25 Suppl B:B64-80. doi: 10.1016/s0149-2918(03)80243-6.

    PMID: 14553867BACKGROUND

  • Charbonnel B, Roden M, Urquhart R, Mariz S, Johns D, Mihm M, Widel M, Tan M. Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens. Diabetologia. 2005 Mar;48(3):553-60. doi: 10.1007/s00125-004-1651-9. Epub 2005 Mar 1.

    PMID: 15739120BACKGROUND

  • Rasouli N, Raue U, Miles LM, Lu T, Di Gregorio GB, Elbein SC, Kern PA. Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am J Physiol Endocrinol Metab. 2005 May;288(5):E930-4. doi: 10.1152/ajpendo.00522.2004. Epub 2005 Jan 4.

    PMID: 15632102BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes MellitusDyslipidemias

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesLipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Armando J. Mendez, Ph.D.
Organization
University of Miami Miller School of Medicine
a.mendez@miami.edu
305-243-5342

Study Officials

  • Armando J Mendez, PhD

    University of Miami

    PRINCIPAL INVESTIGATOR

  • Ronald Goldberg, MD

    University of Miami

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research Associate Professor

Study Record Dates

First Submitted

July 2, 2010

First Posted

July 5, 2010

Study Start

April 1, 2008

Primary Completion

September 1, 2010

Study Completion

September 1, 2010

Last Updated

November 21, 2014

Results First Posted

November 11, 2014

Record last verified: 2014-11

Locations

US(1)