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Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)

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ClinicalTrials.gov Identifier: NCT03288025
Recruitment Status : Recruiting
First Posted : September 19, 2017
Last Update Posted : December 14, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Gustavo A Heresi, MD, MS, The Cleveland Clinic

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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Insulin Resistance Behavioral: Nutrition and Exercise Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) A Randomized Controlled Trial
Actual Study Start Date : September 27, 2017
Estimated Primary Completion Date : December 28, 2022
Estimated Study Completion Date : December 28, 2023


Arm Intervention/treatment
Experimental: Nutrition and Exercise
5 days a week of moderate exercise and biweekly diet counseling on Low Glycemic Index/ Mediterranean Diet for 12 weeks.
Behavioral: Nutrition and Exercise
5 times a week exercise training and biweekly diet counseling for 12 weeks.

No Intervention: Standard of Care
Counseling at baseline on diet as recommended by USDA and on the benefits of regular aerobic exercise.



Primary Outcome Measures :
  1. Insulin Sensitivity [ Time Frame: 5 years ]
    Assessed by the frequently-sampled intravenous glucose tolerance test. Units of assessment in min/uU*mL


Secondary Outcome Measures :
  1. Right Ventricular Global Peak Longitudinal Strain [ Time Frame: 5 years ]
    Assessed by the Doppler Echocardiography 2D longitudinal speckle tracking. Units of assessment in percent.



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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288025


Contacts
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Contact: Chazity Bush 216-444-3702 bushc2@ccf.org
Contact: Gustavo Heresi 216-636-5327 HERESIG@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Chazity Bush    216-444-3702    bushc2@ccf.org   
Principal Investigator: Raed Dweik         
Principal Investigator: Gustavo Heresi         
Sub-Investigator: John Kirwan         
Sponsors and Collaborators
The Cleveland Clinic
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Raed Dweik The Cleveland Clinic
Principal Investigator: Gustavo Heresi The Cleveland Clinic

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Responsible Party: Gustavo A Heresi, MD, MS, Staff, Pulmonary Medicine, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03288025     History of Changes
Other Study ID Numbers: 16-260
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gustavo A Heresi, MD, MS, The Cleveland Clinic:
Insulin Resistance
Inflammation
Right Ventricular Function
Metabolism
Glucose
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Insulin Resistance
Vascular Diseases
Cardiovascular Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases