Anti-Inflammatory Effects of Pioglitazone

NCT00722631 | Completed DMC

• 1 other identifier: PIO 2007
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing evidence that inflammation plays a role in progression and destabilization of atherosclerotic plaque. FDG-PET can visualize activated metabolic activity of inflammatory cells. It is possible that FDG-PET can detect atherosclerotic plaque inflammation and that FDG-PET can monitor the effect of pioglitazone on plaque inflammation.

Conditions

Impaired Glucose Tolerance; Type 2 Diabetes Mellitus; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Effect of treatment on the nominal change in FDG uptake of atherosclerotic plaque from baseline after 4 months of treatment as measured by FDG-PET/CT imaging.

  Baseline and 4 months after treatment

Secondary Outcomes (3)

• Change from baseline in plasma glucose/insulin homeostatic parameters and circulating markers of atherosclerosis

  Baseline and 4 months and 5 years after treatment

• Change from baseline in visceral fat

  Baseline and 4 months and 5 years after treatment

• All cardiovascular events and all cause death for 5 years

  Baseline and 4 months and 5 years after treatment

Study Arms (2)

1

EXPERIMENTAL

up to 30 mg pioglitazone, tablet, orally, once daily

Drug: Pioglitazone

2

ACTIVE COMPARATOR

up to 4 mg/day glimepiride, tablet, orally, once daily

Drug: Glimepiride

Interventions

Pioglitazone DRUG

Subjects who meet eligibility criteria will be titrated up to a maximum of 30 mg/day pioglitazone.

Also known as: CAS number: 111025-46-8, ATC code: A10BG03

1

Glimepiride DRUG

Subjects who meet eligibility criteria will be titrated up to a maximum of 4 mg/day glimepiride.

Also known as: CAS number: 93479-97-1, ATC code: A10BB12

2

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects between the ages of 35 and 85 years
• Subjects with impaired glucose tolerance and type 2 diabetes, who had atherosclerosis detected by carotid ultrasound and/or CT
• Subjects who had vascular FDG uptake by FDG-PET

You may not qualify if:

• Subjects with insulin treatment
• Subjects with uncontrolled diabetes, hypertension, symptomatic coronary artery disease, symptomatic cerebrovascular disease
• Subjects taking more than three antidiabetic medications
• Subjects taking anti-platelet, statins, antidiabetic agents, thiazolidinediones (TZDs) within 8 weeks prior to randomization
• Subjects with cardiac failure (New York Heart Association Class \> III) or left ventricular dysfunction (LVEF \< 40%)
• Subjects with systemic disorders such as active inflammatory, liver, renal, hematopoietic, and malignant disease

Sponsors & Collaborators

• Kurume University: lead

Study Sites (1)

Kurume University Hospital

Kurume, 830-0011, Japan

Location

Related Publications (5)

• Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.

  PMID: 33210751 DERIVED

• Tahara N, Nitta Y, Bekki M, Tahara A, Maeda-Ogata S, Sugiyama Y, Honda A, Igata S, Nakamura T, Sun J, Kurata S, Fujimoto K, Abe T, Matsui T, Yamagishi SI, Fukumoto Y. Two-hour postload plasma glucose and pigment epithelium-derived factor levels are markers of coronary artery inflammation in type 2 diabetic patients. J Nucl Cardiol. 2020 Aug;27(4):1352-1364. doi: 10.1007/s12350-019-01842-5. Epub 2019 Aug 12.

  PMID: 31407236 DERIVED

• Nitta Y, Tahara N, Tahara A, Honda A, Kodama N, Mizoguchi M, Kaida H, Ishibashi M, Hayabuchi N, Ikeda H, Yamagishi S, Imaizumi T. Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging. JACC Cardiovasc Imaging. 2013 Nov;6(11):1172-82. doi: 10.1016/j.jcmg.2013.09.004.

  PMID: 24229770 DERIVED

• Kodama N, Tahara N, Tahara A, Honda A, Nitta Y, Mizoguchi M, Kaida H, Ishibashi M, Abe T, Ikeda H, Narula J, Fukumoto Y, Yamagishi S, Imaizumi T. Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013 Nov;98(11):4438-45. doi: 10.1210/jc.2013-2920. Epub 2013 Sep 12.

  PMID: 24030946 DERIVED

• Mizoguchi M, Tahara N, Tahara A, Nitta Y, Kodama N, Oba T, Mawatari K, Yasukawa H, Kaida H, Ishibashi M, Hayabuchi N, Harada H, Ikeda H, Yamagishi S, Imaizumi T. Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET/CT imaging study of carotid artery and ascending aorta. JACC Cardiovasc Imaging. 2011 Oct;4(10):1110-8. doi: 10.1016/j.jcmg.2011.08.007.

  PMID: 21999871 DERIVED

MeSH Terms

Conditions

Glucose Intolerance; Diabetes Mellitus, Type 2; Atherosclerosis

Interventions

Pioglitazone; glimepiride

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nobuhiro Tahara, MD, PhD

  Kurume University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD

Study Record Dates

• First Submitted: July 22, 2008
• First Posted: July 25, 2008
• Study Start: May 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2012
• Last Updated: September 27, 2012

Record last verified: 2012-09

Locations

JP (1)