Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)

NCT ID: NCT03288025

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-27
• Study Completion Date: 2026-06-30

Brief Summary

The purpose of this study is to investigate the extent to which diet and exercise may improve PAH through the modulation of insulin sensitivity. The central hypothesis is that dysregulated glucose metabolism elicits a response in PAH patients that can be modified by exercise and diet, thereby leading to improvements in pulmonary vascular disease.

Detailed Description

Pulmonary arterial hypertension (PAH) leads to premature death as a consequence of increased pulmonary vascular resistance and right heart failure. PAH-targeted therapies developed over the past 20 years target excessive vasoconstriction. However, the pathobiology of PAH is more complicated, and includes dysregulated vascular cell proliferation, cellular metabolic abnormalities, and inflammation. Even with modern PAH therapies, current outcomes remain poor, with an estimated 3-year survival rate of only 55%. Thus, there is a clear need for more effective therapies, based on better understanding of the pathobiology of the disease.

Insulin resistance has emerged as a potential new mechanism in PAH. Animal models of insulin resistance are associated with PAH, which reverses with the administration of insulin sensitizing drugs. Over the past decade there has been an epidemiologic shift in PAH, where the disease is increasingly observed in older, obese, and diabetic subjects. Low levels of high-density lipoprotein cholesterol in PAH, a feature of insulin resistance, have been observed and found to be a strong independent predictor of PAH mortality. Elevated glycosylated hemoglobin (HbA1c) also correlates with PAH diagnosis and severity. As measured by the OGTT, idiopathic PAH patients have not only insulin resistance, but also an inability to mount an appropriate insulin response to a glucose challenge. These data point to dysfunction in the pancreatic beta cells of PAH patients. It is known that an exercise and low glycemic index diet intervention improves insulin sensitivity in pre-diabetic subjects.

Conditions

Pulmonary Arterial Hypertension; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nutrition and Exercise

5 days a week of moderate exercise and biweekly diet counseling on Low Glycemic Index/ Mediterranean Diet for 12 weeks.

Group Type: EXPERIMENTAL

Nutrition and Exercise

Intervention Type: BEHAVIORAL

5 times a week exercise training and biweekly diet counseling for 12 weeks.

Standard of Care

Counseling at baseline on diet as recommended by USDA and on the benefits of regular aerobic exercise.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Nutrition and Exercise

5 times a week exercise training and biweekly diet counseling for 12 weeks.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Age range between 18-75 years old
• Group 1 PAH, including idiopathic, heritable, drugs and toxin induced, and PAH associated with connective tissue disease, HIV infection and congenital heart disease
• NYHA Class II or III
• ≥ 1 PAH-targeted therapy with a stable dose for ≥ 2 months
• Stable dose of diuretics and rate of supplemental oxygen for the preceding 2 months

Exclusion Criteria

• Decompensated Right Heart Failure
• NYHA Class IV
• Syncope within the previous 3 months
• Cardiac Arrhythmia (except for controlled atrial fibrillation or flutter)
• Baseline supplemental O2 > 4 LPM
• Portal Hypertension
• Pulmonary hypertension due to Lung Disease and Hypoxia
• Pulmonary Hypertension due to Left Heart Disease
• Chronic Thromboembolic Pulmonary Hypertension
• Pulmonary Hypertension associated with systemic diseases such as hematological disorders and sarcoidosis
• Type 2 Diabetes
• Evidence of cardiac ischemia on a graded exercise test

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

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Gustavo A Heresi, MD, MS

Staff, Pulmonary Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raed Dweik, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Gustavo Heresi, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

R01HL130209

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16-260

Identifier Type: -

Identifier Source: org_study_id