Insulin Resistance in Pulmonary Arterial Hypertension

NCT00825266 | Terminated Phase 2 Results

• 2 other identifiers: SU-09052008-1295IRB#7432
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension, Pulmonary

Keywords

pulmonary hypertension & insulin resistance

Outcome Measures

Primary Outcomes (1)

• Insulin Resistance Profile Change - Triglyceride:HDL Cholesterol Ratio

  insulin resistance measured -triglyceride: HDL cholesterol ratio measures at 16 weeks compared with baseline.

  baseline and 16 weeks

Secondary Outcomes (2)

• 6 Minute Walk Test

  Baseline and 16 weeks

• NYHA (New York Heart Association Classification) Changes

  Baseline and 16 weeks

Study Arms (2)

bosentan

ACTIVE COMPARATOR

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

Drug: bosentan

Pioglitazone

ACTIVE COMPARATOR

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

Drug: Pioglitazone

Interventions

bosentan DRUG

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

Also known as: Tracleer

bosentan

Pioglitazone DRUG

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

Also known as: Actos

Pioglitazone

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 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.

You may not qualify if:

• \* 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Insulin Resistance

Interventions

Bosentan; Pioglitazone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazolidinediones; Thiazoles; Azoles

Limitations and Caveats

Study terminated due to poor enrollment

Results Point of Contact

• Title: Roham Zamanian
• Organization: Stanford University

roham.zamanian@stanford.edu

650-725-5495

Study Officials

• Roham T. Zamanian

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: January 16, 2009
• First Posted: January 21, 2009
• Study Start: September 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 31, 2017
• Results First Posted: March 31, 2017

Record last verified: 2017-02

Locations

US (1)