Insulin Resistance in Pulmonary Arterial Hypertension

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00825266
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 19.9
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Sep 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 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 Names: 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 Names: Actos

Outcome Measures

Primary Outcome Measures

1. Insulin Resistance Profile Change - Triglyceride:HDL Cholesterol Ratio [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Roham T. Zamanian, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roham T. Zamanian, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT00825266
• Other Study ID Numbers: SU-09052008-1295; IRB#7432
• First Posted: Jan 21, 2009
• Last Update Posted: Mar 31, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Roham T. Zamanian, Principle Investigator, Stanford University: pulmonary hypertension & insulin resistance
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension; Insulin Resistance; Pioglitazone; Bosentan

Study Results

Participant Flow

Arm/Group Title	Bosentan	Pioglitazone
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg twice daily for 4 weeks, then 125mg BID for duration of study.	Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bosentan	Pioglitazone	Total
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.	Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61	51	56
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bosentan	Pioglitazone
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.	Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.
Measure Participants	1	1
Number [ratio]	-0.22	-1.96

2. Secondary Outcome

Title	6 Minute Walk Test
Description	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.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bosentan	Pioglitazone
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.	Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.
Measure Participants	1	1
Number [meters]	-71	-23

3. Secondary Outcome

Title	NYHA (New York Heart Association Classification) Changes
Description	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}
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bosentan	Pioglitazone
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.	Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.
Measure Participants	1	1
Number [NYHA class]	0	0

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Bosentan		Pioglitazone
Arm/Group Description	Bosentan 62.5 twice daily for 4 weeks, then 125 mg twice daily. bosentan: Bosentan 62.5 mg BID for 4 weeks, then 125mg BID for duration of study.		Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration of the study. Pioglitigone: Pioglitazone 15 mg a day for 4 weeks then Pioglitazone 30 mg a day for the duration fo the study.
All Cause Mortality
	Bosentan		Pioglitazone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bosentan		Pioglitazone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Bosentan		Pioglitazone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

Study terminated due to poor enrollment

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.