Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
| Status: | Recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 5/3/2017 |
| Start Date: | October 2015 |
| End Date: | May 2019 |
| Contact: | Stephen Chan, MD, PhD, FAHA |
| Email: | chansy@pitt.edu |
| Phone: | 412-383-3990 |
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 teh 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.
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 teh 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.
TEST GROUP
Study Visit One
- Consent by PI or Sub-Investigator
- Medical History Review by interview and chart review by PI/Sub-Investigator and
Research Coordinator
- Physical Exam by PI or Sub-Investigator
- Vital Signs by research coordinator
- Pregnancy Test via blood for women who are of child bearing age by research coordinator
- Blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for
microRNA) processed at Presby Lab
- Blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate
PBMCs for generation of iPSCs (in case the skin biopsy does not work). In this case,
the investigator's lab will take the blood and skin biopsy and ship directly on ice to
the investigator's collaborator at Yale (Yibing Qyang).
- ECG, done by research coordinator and read by PI/Sub-Investigator
- 6 Minute Walk Test, done by research coordinator
- Skin Biopsy from underarm or inner thigh by Dr. Laura Ferris. Patients will be escorted
by research coordinator to the 3rd floor of Falk to the Dermatology Clinic.
All visits will occur in Outpatient Cardiology at Presby 5B clinic except the Skin Biopsy as
noted. This visit will last 6-7 hours.
Study Visit Two
- Right Heart Catheterization will be done in Presby's Cath Lab 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, the investigator
will NOT need to perform exercise testing. In that case the patient will have
resting echocardiography. (determined by PI/Sub-Investigator)
- In all other cases, patients will have an Exercise Right Heart Catheterization and
a Rest and Stress Echocardiography. (Determined by PI/Sub-Investigator
- Resting Echocardiogram completed in the echocardiogram lab at Presby by a trained
sonographer. Results given to PI/Sub-Investigator. Duration ~ 30-45 minutes
- Exercise Echocardiogram completed in Presby's cath lab. If patient unable to exercise
medication (Dobutamine) will be given. Duration ~ 1-2 hours
- Exercise Right Heart Catheterization will be completed in Presby Cath Lab by Dr.
Ishizawar. Duration ~ 2-3 hours
CONTROL GROUP
Study Visit One
- Consent by PI or Sub-Investigator
- Medical History Review by interview and chart review by PI/Sub-Investigator and
Research Coordinator
- Physical Exam by PI or Sub-Investigator
- Vital Signs by research coordinator
- Pregnancy Test via urine for women who are of child bearing age by research coordinator
- Blood work (kidney/liver, blood count, coagulation, iron studies, and plasma for
microRNA)
- Blood draw (3.5 tablespoons), drawn by research coordinator. This blood is to isolate
PBMCs for generation of iPSCs (in case the skin biopsy does not work). In this case,
the investigator's lab will take the blood and skin biopsy and ship directly on ice to
the investigator's collaborator at Yale (Yibing Qyang).
- ECG, done by research coordinator and read by PI/Sub-Investigator
- 6 Minute Walk Test, done by research coordinator
- Skin Biopsy from underarm or inner thigh by Dr. Laura Ferris. Patients wil be escorted
by research coordinator to the 3rd floor of Falk to the Dermatology Clinic.
All visits will occur in Outpatient Cardiology at Presby 5B clinic except the Skin Biopsy as
noted. This visit will last 6-7 hours.
Study Visit One
- Consent by PI or Sub-Investigator
- Medical History Review by interview and chart review by PI/Sub-Investigator and
Research Coordinator
- Physical Exam by PI or Sub-Investigator
- Vital Signs by research coordinator
- Pregnancy Test via blood for women who are of child bearing age by research coordinator
- Blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for
microRNA) processed at Presby Lab
- Blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate
PBMCs for generation of iPSCs (in case the skin biopsy does not work). In this case,
the investigator's lab will take the blood and skin biopsy and ship directly on ice to
the investigator's collaborator at Yale (Yibing Qyang).
- ECG, done by research coordinator and read by PI/Sub-Investigator
- 6 Minute Walk Test, done by research coordinator
- Skin Biopsy from underarm or inner thigh by Dr. Laura Ferris. Patients will be escorted
by research coordinator to the 3rd floor of Falk to the Dermatology Clinic.
All visits will occur in Outpatient Cardiology at Presby 5B clinic except the Skin Biopsy as
noted. This visit will last 6-7 hours.
Study Visit Two
- Right Heart Catheterization will be done in Presby's Cath Lab 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, the investigator
will NOT need to perform exercise testing. In that case the patient will have
resting echocardiography. (determined by PI/Sub-Investigator)
- In all other cases, patients will have an Exercise Right Heart Catheterization and
a Rest and Stress Echocardiography. (Determined by PI/Sub-Investigator
- Resting Echocardiogram completed in the echocardiogram lab at Presby by a trained
sonographer. Results given to PI/Sub-Investigator. Duration ~ 30-45 minutes
- Exercise Echocardiogram completed in Presby's cath lab. If patient unable to exercise
medication (Dobutamine) will be given. Duration ~ 1-2 hours
- Exercise Right Heart Catheterization will be completed in Presby Cath Lab by Dr.
Ishizawar. Duration ~ 2-3 hours
CONTROL GROUP
Study Visit One
- Consent by PI or Sub-Investigator
- Medical History Review by interview and chart review by PI/Sub-Investigator and
Research Coordinator
- Physical Exam by PI or Sub-Investigator
- Vital Signs by research coordinator
- Pregnancy Test via urine for women who are of child bearing age by research coordinator
- Blood work (kidney/liver, blood count, coagulation, iron studies, and plasma for
microRNA)
- Blood draw (3.5 tablespoons), drawn by research coordinator. This blood is to isolate
PBMCs for generation of iPSCs (in case the skin biopsy does not work). In this case,
the investigator's lab will take the blood and skin biopsy and ship directly on ice to
the investigator's collaborator at Yale (Yibing Qyang).
- ECG, done by research coordinator and read by PI/Sub-Investigator
- 6 Minute Walk Test, done by research coordinator
- Skin Biopsy from underarm or inner thigh by Dr. Laura Ferris. Patients wil be escorted
by research coordinator to the 3rd floor of Falk to the Dermatology Clinic.
All visits will occur in Outpatient Cardiology at Presby 5B clinic except the Skin Biopsy as
noted. This visit will last 6-7 hours.
Inclusion Criteria:
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.
3. clinical indication for RHC and advanced CPET with documentation of a physician
referral. These indications include dyspnea, dyspnea on exertion, heart failure, and
exercise intolerance where the etiology is not known or the symptoms are out of
proportion to any documented co-morbidities
4. Insurance pre-approval for RHC and advanced CPET for subjects living in the United
States and who have health insurance; no such pre-approval is necessary for subjects
living outside the United States
5. No records of a prior RHC documenting normal pulmonary arterial and right heart
filling pressures with normal cardiac output.
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:
Test Group:
1. Inability to exercise on a stationary bike
2. Impaired decision making capacity
3. Inability to consent to procedures
4. Children less than 18 years of age and adults older than 60 years of age
5. Current pregnancy
6. Inability to tolerate CPET, echocardiography, or PET scan
7. Prior RHC documenting normal pulmonary arterial and right heart filling pressures
with normal cardiac output.
Control Group:
1. Impaired decision making capacity 2. Inability to consent to procedures 3. Current
pregnancy 4. Children less than 18 years of age and adults older than 60 years of age 5.
Currently on chronic anticoagulation (warfarin, low molecular weight heparin, Factor Xa
inhibitors).
We found this trial at
1
site
200 Lothrop St
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Phone: 412-383-6990
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
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