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Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension

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ClinicalTrials.gov Identifier: NCT02594917
Recruitment Status : Recruiting
First Posted : November 3, 2015
Last Update Posted : June 25, 2020
Sponsor:
Information provided by (Responsible Party):
Stephen Y. Chan, University of Pittsburgh

Tracking Information
First Submitted Date October 29, 2015
First Posted Date November 3, 2015
Last Update Posted Date June 25, 2020
Study Start Date October 2015
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 2, 2015)
  • 6 minute walk distance (meters) [ Time Frame: baseline ]
    In the TEST group, the investigators will measure 6 minute walk distance
  • Pulmonary arterial pressure (mm Hg) [ Time Frame: baseline ]
    In the TEST group, the investigators will measure pulmonary arterial pressure by right heart catheterization at rest and with exercise.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
Official Title Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
We are generating inducible pluripotent stem cells from blood and skin biopsies from participants.
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.
Condition
  • Iron-sulfur Cluster Deficiency
  • Pulmonary Hypertension
  • Friedreich Ataxia
Intervention
  • 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
Study Groups/Cohorts
  • 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.
    Interventions:
    • 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.
    Intervention: Other: Blood draw
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 3, 2019)
11
Original Estimated Enrollment
 (submitted: November 2, 2015)
20
Estimated Study Completion Date September 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Stephen Chan, MD, PhD, FAHA 412-383-3990 chansy@pitt.edu
Contact: Annie Watson, MPH 412-647-4964 watsonam3@upmc.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02594917
Other Study ID Numbers STUDY19030124
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Stephen Y. Chan, University of Pittsburgh
Study Sponsor University of Pittsburgh
Collaborators Not Provided
Investigators
Principal Investigator: Stephen Chan, MD, PhD, FAHA University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date June 2020