Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)
Primary Purpose
Pulmonary Arterial Hypertension, Insulin Resistance
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Nutrition and Exercise
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Insulin Resistance, Inflammation, Right Ventricular Function, Metabolism, Glucose
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
Sites / Locations
- Cleveland Clinic Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Nutrition and Exercise
Standard of Care
Arm Description
5 days a week of moderate exercise and biweekly diet counseling on Low Glycemic Index/ Mediterranean Diet for 12 weeks.
Counseling at baseline on diet as recommended by USDA and on the benefits of regular aerobic exercise.
Outcomes
Primary Outcome Measures
Insulin Sensitivity
Assessed by the frequently-sampled intravenous glucose tolerance test. Units of assessment in min/uU*mL
Secondary Outcome Measures
Right Ventricular Global Peak Longitudinal Strain
Assessed by the Doppler Echocardiography 2D longitudinal speckle tracking. Units of assessment in percent.
Full Information
NCT ID
NCT03288025
First Posted
August 31, 2017
Last Updated
March 23, 2023
Sponsor
The Cleveland Clinic
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT03288025
Brief Title
Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)
Official Title
Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) A Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 27, 2017 (Actual)
Primary Completion Date
February 18, 2022 (Actual)
Study Completion Date
December 18, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension, Insulin Resistance
Keywords
Insulin Resistance, Inflammation, Right Ventricular Function, Metabolism, Glucose
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nutrition and Exercise
Arm Type
Experimental
Arm Description
5 days a week of moderate exercise and biweekly diet counseling on Low Glycemic Index/ Mediterranean Diet for 12 weeks.
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Counseling at baseline on diet as recommended by USDA and on the benefits of regular aerobic exercise.
Intervention Type
Behavioral
Intervention Name(s)
Nutrition and Exercise
Intervention Description
5 times a week exercise training and biweekly diet counseling for 12 weeks.
Primary Outcome Measure Information:
Title
Insulin Sensitivity
Description
Assessed by the frequently-sampled intravenous glucose tolerance test. Units of assessment in min/uU*mL
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Right Ventricular Global Peak Longitudinal Strain
Description
Assessed by the Doppler Echocardiography 2D longitudinal speckle tracking. Units of assessment in percent.
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raed Dweik, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gustavo Heresi, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)
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