Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension

NCT02594917 | Completed

• 1 other identifier: STUDY19030124
• Study Type: observational
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are performing this research study to determine whether having low iron-sulfur cluster levels can cause a disease known as pulmonary hypertension (PH). PH is defined as abnormally high blood pressure in the arteries of the lungs. Usually, small specialized structures inside each human cell called mitochondria are in charge of generating energy within lung arteries for normal function. During situations of disease or stress, lung arteries undergo a change in the function of mitochondria, resulting in the development of PH. In studies on mice, investigators have learned that alterations in the production of specific metal complexes called iron-sulfur clusters are responsible for these changes. This makes it more likely that mice will develop PH. In this study, the investigators want to find out if alteration of iron-sulfur cluster formation leads to increased likelihood of developing PH in humans.

Conditions

Iron-sulfur Cluster Deficiency; Pulmonary Hypertension; Friedreich Ataxia

Outcome Measures

Primary Outcomes (2)

• 6 minute walk distance (meters)

  In the TEST group, the investigators will measure 6 minute walk distance

  baseline

• Pulmonary arterial pressure (mm Hg)

  In the TEST group, the investigators will measure pulmonary arterial pressure by right heart catheterization at rest and with exercise.

  baseline

Study Arms (2)

Test Group

The study population will include ten patients (ages 18-60 yrs) with confirmed mutations of the iron-sulfur cluster biogenesis complex of proteins and experiencing dyspnea, heart failure, or exercise intolerance.

Procedure: Right Heart Catheterization; Other: Blood draw

Control Group

It will also include ten additional patients (ages 18-60 yrs) who are unaffected first-degree family members of the above subjects.

Other: Blood draw

Interventions

Right Heart Catheterization PROCEDURE

Some participants (i.e., those that are willing and able) will undergo a Right Heart Catheterization to check Cardiopulmonary function.

Test Group

Blood draw OTHER

Test and control group will be asked to give 20 ml of blood samples

Control Group; Test Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

The study population will include ten patients (ages 18-60 yrs) with confirmed mutations of the iron-sulfur cluster biogenesis complex of proteins. It will also include ten additional patients (ages 18-60 yrs) who are unaffected first-degree family members of the above subjects.

You may qualify if:

• Consenting individuals age 18-60 years of age
• Have a confirmed genetic homozygous mutation (including ISCU1/2, FXN, BOLA3, NFU1) that causes the impairment of iron-sulfur cluster formation; such a subject will not be excluded from this study even if that patient's first degree relative(s) does not enroll in this pilot study.
• Consenting individuals age 18-60 years of age
• First degree family member (mother, father, sister, brother, son, or daughter) of recruited individual in the test group
• Have a confirmed heterozygous genetic mutation (including ISCU1/2, FXN, BOLA3, NFU1)

You may not qualify if:

• Impaired decision making capacity
• Inability to consent to procedures
• Children less than 18 years of age and adults older than 60 years of age
• Current pregnancy

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

We are generating inducible pluripotent stem cells from blood and skin biopsies from participants.

MeSH Terms

Conditions

Hypertension, Pulmonary; Friedreich Ataxia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stephen Chan, MD, PhD, FAHA

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: November 3, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

US (1)