Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years - 60 Years
Gender	All

More Inclusion & Exclusion Criteria

INCLUSION CRITERIA for Test Group: 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. INCLUSION CRITERIA for Control Group: 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 for Test and Control Group: 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02594917
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Pittsburgh
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Stephen Chan, MD, PhD, FAHA
Principal Investigator Affiliation	University of Pittsburgh
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Iron-sulfur Cluster Deficiency, Pulmonary Hypertension, Friedreich Ataxia

Additional Details

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.

Arms & Interventions

Arms

: 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.

: Control Group

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

Interventions

Procedure: - Right Heart Catheterization

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

Other: - Blood draw

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Status

Recruiting

Address

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213

Site Contact

Stephen Chan, M.D., Ph.D., F.A.H.A.

chansy@pitt.edu

412-383-6990