Dysregulation of Lipid Metabolism and Right Ventricular Function in PAH

NCT02631421 | Completed

• 1 other identifier: 140983
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Right ventricular (RV) failure is the predominant cause of death in pulmonary arterial hypertension (PAH). No RV-specific therapies are available, in part because the underlying mechanisms of RV dysfunction are poorly understood. Given the heart's preference for fatty acids (FA) as an energy source, a deeper understanding of FA metabolism may shed light on RV adaptation to elevated afterload in PAH. The purpose of this study is to test the hypothesis that defects in fatty acid metabolism are common in PAH and contribute to RV failure. The investigators will measure peripheral and transcardiac lipid and glucose metabolites in PAH patients in comparison with patients with pulmonary venous hypertension and no evidence of pulmonary hypertension. The investigators will also correlate metabolites with concurrent measurement of right ventricular function.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• Peripheral blood oleoylcarnitine in PAH versus control

  At time of clinic visit, within 24 hrs prior to right heart catheritization

• Percent change across the cardiac circulation of oleate and the glucose/lactate ratio.

  The combination of these findings will indicate if there is a decreased reliance on FAO and and increased glycolysis

  At time of right heart catheterization

Secondary Outcomes (6)

• Correlation of oleoylcarnitine, other acylcarnitines and free fatty acids with the homeostatic index of insulin resistance, tricuspid annular plane systolic excursion, and six minute walk distance

  At time of clinic visit, within 24hrs prior to right heart catheritization

• Correlation of the trans-cardiac gradient of oleate and lactate/glucose with right ventricular ejection fraction on cardiac MRI and six minute walk distance.

  At time of right heart catheterization

• Measurement of trans-cardiac acylcarnitines

  At time of right heart catheterization

• Measurement of trans-cardiac and trans-pulmonary glucose metabolites

  At time of right heart catheterization

• Measurement of trans-cardiac and trans-pulmonary lipid metabolites

  At time of right heart catheterization

Study Arms (2)

Pulmonary Arterial Hypertension

Clinical diagnosis of pulmonary arterial hypertension

Procedure: Blood Sampling; Other: Cardiac MRI

Healthy subjects and patients with other causes of PH

Patients referred for right heart catheterization who do not have PAH

Procedure: Blood Sampling

Interventions

Blood Sampling PROCEDURE

Healthy subjects and patients with other causes of PH; Pulmonary Arterial Hypertension

Cardiac MRI OTHER

Pulmonary Arterial Hypertension

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

PAH

You may qualify if:

• ≥ 18 years old
• Scheduled to undergo cardiac catheterization (right ± left heart catheterization) and/or electrophysiology study in the VHVI cardiac catheterization laboratory (CCL)/electrophysiology laboratory (EP lab)
• Hemoglobin value ≥ 10 g/dL or hematocrit of ≥ 30% (measured on clinically-indicated blood draw within 30 days or a point-of-care measurement in CCL/EP Laboratory if clinically-indicated value is not available)

You may not qualify if:

• Any individual that is anemic and has a hemoglobin value \< 10 g/dL and hematocrit of \< 30% will be excluded from the study.
• If a physician performing the procedure believes that performing the extra steps and /or acquiring the additional blood samples will delay or otherwise compromise participants' care, he/she can abandon acquisition of those data at his/her discretion.
• Contraindication to cardiac MRI (applies only to patients undergoing CMR as part of this protocol).
• Implanted ferromagnetic material
• Glomerular filtration rate \< 60mL/min (measured on clinically-indicated blood draw within 30 days of CMR or a point-of-care measurement in the CMR Laboratory if clinically-indicated GFR is not available)

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Univeristy

Nashville, Tennessee, 37203, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Evan Brittain, MD, MSCI

  Vanderbilt Univerisy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 12, 2014
• First Posted: December 16, 2015
• Study Start: January 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 16, 2019

Record last verified: 2019-07

Locations

US (1)