Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension

NCT ID: NCT02594917

Last Updated: 2023-09-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 13 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2023-09-01

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.

Detailed Description

Test group:

The study will include two visits for the test group:

At visit one there will be required and optional research activities as the following:

Required research activities:

-Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate PBMCs for generation of iPSCs.If patient did not want to give a blood sample we will ask if willing to give a urine sample. A clinical research coordinator will give the patient a plastic container and will explain how use it.

The following research activities will be optional at visit one:

1. Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for microRNA) processed at Presby Lab. This will be required if the patient approved to do right heart cath.

2. Electrocardiogram.

3. 6 Minute Walk Test.

4. Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if patients agree to do, if not, we will only get a blood sample)

5. Resting Echocardiogram

This visit will last 7-8 hours.

Study Visit Two:

This will include optional Right Heart Catheterization.

• Right Heart catheterization by PI/Sub-Investigator. Duration ~ 3 hours

• IF the results show that the pressure in the lung vessels is elevated without exercise AND there is no other abnormality in the heart function, we will NOT do exercise testing.
• IF the patients are physically able to perform exercise testing/agree to do an exercise testing, patients will have an Exercise Right Heart catheterization and a Rest and Stress Echocardiography. (Determined by PI/Sub-Investigator
• All participants who will do right heart catheterization will have to do a pregnancy test before the procedure.
• Exercise Echocardiogram completed in. If patient unable to exercise medication (Dobutamine) will be given. Duration ~ 1-2 hours
• Exercise Right Heart catheterization Duration ~ 2-3 hours

CONTROL GROUP

Control group will only have one visit. At this visit there will be a minimum required research activity to participate in the study and this will include:

-Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate PBMCs for generation of iPSCs. If participant did not want to give a blood sample we will ask if willing to give a urine sample.

The following research activists will be optional at visit one:

1. Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for microRNA) processed at Presby Lab. This will be required if the patient approved to do right heart cath.

2. ECG, done by research coordinator and read by PI/Sub-Investigator.

3. 6 Minute Walk Test, done by research coordinator, if patient could perform.

4. Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if patients agree to do, if not, we will only get a blood sample) This visit will last 6-7 hours.

Conditions

Iron-sulfur Cluster Deficiency; Pulmonary Hypertension; Friedreich Ataxia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Right Heart Catheterization

Intervention Type: PROCEDURE

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

Blood draw

Intervention Type: OTHER

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

Control Group

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

Blood draw

Intervention Type: OTHER

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

Interventions

Right Heart Catheterization

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

Intervention Type: PROCEDURE

Blood draw

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Consenting individuals age 18-60 years of age

2. 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.

1. Consenting individuals age 18-60 years of age

2. First degree family member (mother, father, sister, brother, son, or daughter) of recruited individual in the test group

3. Have a confirmed heterozygous genetic mutation (including ISCU1/2, FXN, BOLA3, NFU1)

Exclusion Criteria

1. Impaired decision making capacity

2. Inability to consent to procedures

3. Children less than 18 years of age and adults older than 60 years of age

4. Current pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Stephen Y. Chan

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen Chan, MD, PhD, FAHA

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

STUDY19030124

Identifier Type: -

Identifier Source: org_study_id