Coronary Artery Disease in Patients With Friedreich's Ataxia

NCT04649866 | Completed

• 1 other identifier: STUDY20070248
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Friedreich's ataxia is a debilitating, inherited disease cause by mutations in a protein called frataxin (FXN). FXN is one of several proteins that controls the production of iron-sulfur clusters, molecules that are essential for energy production in our cells as well as repair of our genetic code embedded in DNA molecules. Friedreich's ataxia (FRDA) and deficiency of FXN results in a nerve disease affecting coordination and a condition called hypertrophic cardiomyopathy (HCM), marked by an abnormal thickening of the heart. Patients with HCM can then develop pulmonary hypertension (PH), a deadly condition of the blood vessels of the lung. While most of the research in FRDA has focused on nerves and heart muscle, alterations in blood vessels of the heart and lung may worsen disease in FRDA. But, the role of FXN in these blood vessels has never been defined. Investigators pilot data suggest that Frataxin (FXN ) deficiency can control senescence and downstream function in various types of Endothelial cells (ECs), investigators hypothesize that Friedreich's Ataxia (FRDA) patients may demonstrate endothelial cells EC abnormalities throughout the vasculature potentially before overt cardiomyopathy develops.

Conditions

Friedreich Ataxia

Keywords

Friedreich's ataxia; frataxin; cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• vasomotor tone

  We will quantify vasomotor tone in regard to level of vasoconstriction and vasodilation at rest and in response to pharmacologic stimulation

  2-4 hours

Study Arms (2)

Test group

EXPERIMENTAL

Endothelial dysfunction will be tested using Strain-gauge plethysmography to measure forearm blood flow during infusions of acetylcholine \[ACh\] and sodium nitroprusside \[SNP\]

Diagnostic Test: plethysmography

Control group

ACTIVE COMPARATOR

Endothelial dysfunction will be tested using Strain-gauge plethysmography to measure forearm blood flow during infusions of acetylcholine \[ACh\] and sodium nitroprusside \[SNP\]

Diagnostic Test: plethysmography

Interventions

plethysmography DIAGNOSTIC_TEST

Forearm blood flow (FBF) measurements in both arms will be made using venous occlusion strain-gauge plethysmography prior to the initiation of any intra-arterial infusions. All FBF measurements will be expressed as mL/min per 100-1 mL forearm volume according to prior studies and the Whitney method.1, 2 Resting baseline FBF will be measured at least 30 minutes after venous and arterial catheter placement to ensure that blood flows in the cannulated arms are stabilized. We will measure FBF during the last 2 minutes of each infusion period. Infusions of individual vasoactive medications will occur over a 15-minute interval. There will be a 25-minute washout between vasoactive medications. Cumulative dose response curves will be constructed over 5-minute incremental infusions. We will proceed in the following order: * SNP 0.8, 1.6 and 3.2 mcg/min * ACh 7.5, 15 and 30 mcg/min * Normal saline

Control group; Test group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18
• Has FRDA
• Has recent clinical echocardiography data confirming normal cardiac function

You may not qualify if:

• Patients younger than 18
• Has abnormal cardiac function

Sponsors & Collaborators

• University of Pittsburgh: lead
• Friedreich's Ataxia Research Alliance: collaborator

Study Sites (1)

Montefiore Hospital Clinical and Translational Research Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Friedreich Ataxia; Cardiomyopathies

Interventions

Plethysmography

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Stephen Chan, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 2, 2020
• Study Start: February 15, 2021
• Primary Completion: August 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 8, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will available starting 6 months after publication
• Access Criteria: The Comprehensive Pulmonary Hypertension Program and Comprehensive lung center shall require secondary investigators to obtain regulatory approval prior its provision of de-identified information to the secondary investigators

Locations

US (1)