Insulin Resistance in Pulmonary Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT00825266
• Recruitment Status: Terminated
• First Posted: January 21, 2009
• Results First Posted: March 31, 2017
• Last Update Posted: March 31, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): Roham T. Zamanian, Stanford University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension, Pulmonary	Drug: bosentan; Drug: Pioglitazone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Bosentan and Pioglitazone on Insulin Resistance in Pulmonary Arterial Hypertension
• Study Start Date: September 2008
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: bosentan; Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily.	Drug: bosentan; Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.; Other Name: Tracleer
Active Comparator: Pioglitazone; Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study.	Drug: Pioglitazone; Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.; Other Name: Actos

Outcome Measures

Primary Outcome Measures :

1. Insulin Resistance Profile Change - Triglyceride:HDL Cholesterol Ratio [ Time Frame: baseline and 16 weeks ]
   insulin resistance measured -triglyceride: HDL cholesterol ratio measures at 16 weeks compared with baseline.

Secondary Outcome Measures :

1. 6 Minute Walk Test [ Time Frame: Baseline and 16 weeks ]
   6 minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes.It assess the disease severity of the subject at 16 week compared to the baseline.
2. NYHA (New York Heart Association Classification) Changes [ Time Frame: Baseline and 16 weeks ]

   New York Heart Classification(NYHA) changes measured at 16 weeks compared with baseline.

   NYHA Classification:

   NYHA class I:no symptoms and no limitation in ordinary physical activity NYHA class II:Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity NYHA class III:Marked limitation in activity due to symptoms, even during less-than-ordinary activity, NYHA class IV:Severe limitations. Experiences symptoms even while at rest. {Higher NYHA class represent worse symptoms}

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Roham T. Zamanian; Stanford University

More Information

• Responsible Party: Roham T. Zamanian, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT00825266
• Other Study ID Numbers: SU-09052008-1295; IRB#7432
• First Posted: January 21, 2009
• Results First Posted: March 31, 2017
• Last Update Posted: March 31, 2017
• Last Verified: February 2017

Keywords provided by Roham T. Zamanian, Stanford University:

pulmonary hypertension & insulin resistance

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension; Insulin Resistance; Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Lung Diseases; Respiratory Tract Diseases; Pioglitazone; Bosentan; Hypoglycemic Agents; Physiological Effects of Drugs; Antihypertensive Agents; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action