Metabolic Effects of Thiazolidinediones in Chronic Kidney Disease

NCT00368017 | Terminated Phase 2

• 1 other identifier: 060042
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The substantially increased cardiovascular morbidity and mortality rates in chronic kidney disease (CKD) patients cannot be sufficiently explained by traditional coronary risk factors. It is apparent that inflammation of the vessel wall plays an essential role in the pathophysiology of atherosclerosis, and the strong association between elevated inflammatory biomarkers and cardiovascular death further supports this mechanism. Approximately 50% of the mortality in this population of patients is attributable to cardiovascular disease. Insulin resistance is also a common problem in uremic patients. It has been shown that insulin resistance may contribute to atherosclerotic cardiovascular disease. An intriguing observation in CKD patients with advanced uremia is that the metabolic profile of these patients is characterized by persistent low-grade inflammation, a state of insulin resistance, and significantly increased prevalence of atherosclerosis. It is possible that these metabolic derangements can be the inciting factors for development and progression of uremic atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated nuclear transcription factor found in cells of the immune system and the vasculature, where it exerts an overall protective effect on the development of atherosclerosis, in part through modulation of inflammation. The agonists for PPAR-gamma improve not only the insulin resistance, but also have profound beneficial effects on inflammation, oxidative stress, endothelium, and lipid metabolism. In this proposal, the investigators hypothesize that short-term administration of a PPAR-gamma agonist (pioglitazone) will improve the inflammatory state, insulin resistance, and endothelial dysfunction in chronic kidney disease patients with advanced uremia.

Conditions

Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• A decrease in C-reactive protein (CRP) levels

  14 weeks

Secondary Outcomes (2)

• Improved insulin resistance

  14 weeks

• Improved endothelium-dependent vasodilation

  14 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: pioglitazone

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

pioglitazone DRUG

30 mg once a day for 12 weeks

Also known as: ACTOS

1

placebo DRUG

1 pill once a day for 12 weeks

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Stage 3 or 4 chronic kidney disease as measured by a Modification in Diet in Renal Disease Study (MDRD) estimate of between 15 ml/min and 59 ml/min.
• Age between 18 and 75 years old.
• Patients without hospitalization for cardiac or infection related morbidity over the previous four weeks (due to the potential confounding effects on baseline study variables).
• Patients who are able to provide consent to participate in the study.

You may not qualify if:

• Patients with prior documented diagnosis of diabetes mellitus.
• Patients with fasting blood glucose \> 110mg/dL.
• Prisoners, patients will significant mental illness, pregnant women, and other vulnerable populations.
• Patients with active hepatic disease and/or ALT \> 2.5 times upper limit of normal.
• Patients with history of congestive heart failure and NYHA Class III-IV symptoms at any time.
• Patients for whom living donor renal transplantation is already scheduled or in the process of being evaluated, as these patients will be unlikely to complete study protocols before transplantation.
• Patients with severe co-morbid conditions (eg, symptomatic hepatic cirrhosis, metastatic cancer, HIV infection with AIDS).
• Patient with active inflammatory process (eg., SLE, rheumatoid arthritis, gout) for which they are currently receiving immune modulating medications.
• Patients who are on corticosteroid therapy.
• Patients who do not consent to participate in the study.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Alp Ikizler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 23, 2006
• First Posted: August 24, 2006
• Study Start: April 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: November 3, 2010

Record last verified: 2010-11

Locations

US (1)