Insulin Resistance in Pulmonary Arterial Hypertension

Hypertension, Pulmonary Clinical Trial

Official title:

The Effect of Bosentan and Pioglitazone on Insulin Resistance in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00825266
• Other study ID #: SU-09052008-1295
• Secondary ID: IRB#7432
• Status: Terminated
• Phase: Phase 4
• First received: January 16, 2009
• Last updated: July 22, 2011
• Start date: September 2008
• Est. completion date: May 2010

Study information

• Verified date: July 2011
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Patients with PAH must be stable on therapy for at least 3 months prior to enrollment in the trial. We will include patients with IPAH and FPAH 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 ET-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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Insulin Resistance

Intervention

Drug:
• bosentan
Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.
• Pioglitigone
Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Resistance Profile Change
Secondary	6 minute walk test
Secondary	NYHA classification changes