Insulin Resistance in Pulmonary Arterial Hypertension

NCT ID: NCT00825266

Last Updated: 2017-03-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-05-31

Brief Summary

The purpose of this study is to evaluate 1) the incidence of insulin resistance (a pre-diabetic state) in patients with pulmonary hypertension, and 2) test the utility of a validated PH therapy (Tracleer) versus Pioglitazone in the treatment of those patients found to have insulin resistance.

Detailed Description

The Effect of Bosentan and Pioglitazone on Insulin Resistance in Pulmonary Arterial Hypertension ,is a study evaluating the incidence of insulin resistance in patients with pulmonary hypertension and testing the utility of a validated PH therapy(Tracleer) versus Pioglitazone in the treatment of those patients found to have insulin resistance.Patients with PAH must be stable on therapy for at least 3 months are considered for enrollment in this study.With the exception of PAH, subjects must be free of major medical illnesses, including diabetes mellitus ,malignancy or significant hepatic or renal disease.

Conditions

Hypertension, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

bosentan

Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily.

Group Type: ACTIVE_COMPARATOR

bosentan

Intervention Type: DRUG

Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.

Pioglitazone

Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study.

Group Type: ACTIVE_COMPARATOR

Pioglitazone

Intervention Type: DRUG

Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.

Interventions

bosentan

Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.

Intervention Type: DRUG

Pioglitazone

Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.

Intervention Type: DRUG

Other Intervention Names

Tracleer; Actos

Eligibility Criteria

Inclusion Criteria

Patients with Pulmonary Arterial Hypertension (PAH) must be stable on therapy for at least 3 months prior to enrollment in the trial. We will include patients with idiopathic PAH and Familial PAH as well as PAH associated with collagen vascular disease or drug or toxin exposure. With the exception of PAH, subjects must be free of major medical illnesses, including diabetes mellitus (must have fasting plasma glucose < 126 mg/dL and taking no anti-hyperglycemic agent), malignancy or significant hepatic or renal disease. Subjects may be hypertensive and on anti-hypertensive medications as long as blood pressure is < 150/100 mm Hg. Subjects may also be dyslipidemic and/or taking drugs to improve abnormalities of lipid metabolism, but they will be excluded if they are taking medications known to alter insulin sensitivity, including glucocorticoids, niacin, anti-retrovirals, thiazolidinediones, or metformin. Use of oral contraceptives or estrogen and/or progesterone replacement therapy is permitted. Weight must be stable and the subjects agree not to change their eating habits or exercise regimen during the study period. There will be no restrictions with regard to race or socioeconomic status, and the racial/ethnic composition of the study population will be reflective of the communities surrounding the Stanford University Medical Center.

Exclusion Criteria

• Vulnerable subject status.

• Concurrent Endothelin-1 antagonist therapy
• Concurrent Thiazolidinedione therapy
• New York Heart Class III or IV
• PAH related to other etiologies.
• Diabetes Mellitus with Fasting Glucose Levels > 126 mg/dL
• Allergy or hypersensitivity to pioglitazone or bosentan administration.
• Current treatment with statin therapy.
• Initiation of PAH therapy (prostacyclin analogues, phosphodiesterase-5 inhibitors) within three months of enrollment.
• Inability or unwillingness to avoid systemic steroid containing medications for four months. Inhaled steroid use is acceptable.
• Current or recent use or planned treatment with: glyburide, cyclosporine, nilotinib, nisoldipine, ranolazine, thioridazine
• Hepatic transaminases > 2x the upper limit of normal at the center at screening.
• Current or recent (< 6 months) chronic heavy alcohol consumption.
• Current use of another investigational drug (non-FDA approved) for PAH.
• Lung transplant recipients.
• History of myositis.
• Renal failure (Cr 2.0).
• Hospitalized or acutely ill.
• Chronic liver disease (cirrhosis, chronic hepatitis, etc.).
• Abnormalities of the arm or hand or radical mastectomy (preventing brachial artery ultrasound).
• Pregnant or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Roham T. Zamanian

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roham T. Zamanian

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

IRB#7432

Identifier Type: -

Identifier Source: secondary_id

SU-09052008-1295

Identifier Type: -

Identifier Source: org_study_id