Pulmonary Arterial HypertensionNCT03288025
Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE)
A study testing Nutrition and Exercise in people with Pulmonary Arterial Hypertension and Insulin Resistance, run by The Cleveland Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension, Insulin Resistance
- What is being tested?
- Nutrition and Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2017to 30 Jun 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) A Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Nutrition and Exercise
- Keywords
- Insulin Resistance, Inflammation, Right Ventricular Function, Metabolism, Glucose
- Medical subject headings
- Pulmonary Arterial Hypertension, Insulin Resistance, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutrition and ExerciseBehavioural
5 times a week exercise training and biweekly diet counseling for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Nutrition and Exercise | Experimental | 5 days a week of moderate exercise and biweekly diet counseling on Low Glycemic Index/ Mediterranean Diet for 12 weeks. Receives: Behavioral: Nutrition and Exercise |
| Standard of Care | No intervention | Counseling at baseline on diet as recommended by USDA and on the benefits of regular aerobic exercise. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Assessed by the frequently-sampled intravenous glucose tolerance test. Units of assessment in min/uU*mL
Measured: 5 years
Secondary outcomes (1)
Right Ventricular Global Peak Longitudinal Strain
Assessed by the Doppler Echocardiography 2D longitudinal speckle tracking. Units of assessment in percent.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start27 Sep 2017
- Primary completion18 Feb 2022
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Gustavo A Heresi, MD, MS, The Cleveland Clinic
- Investigators
- Raed Dweik, MD, Principal investigator, The Cleveland ClinicGustavo Heresi, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03288025
- Sponsor's protocol ID
- 16-260
- Other IDs
- R01HL130209
- Status last verified
- Oct 2026
- First submitted
- 31 Aug 2017
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No