Iron-sulfur Cluster DeficiencyNCT02594917
Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
An observational study of Iron-sulfur Cluster Deficiency and Pulmonary Hypertension, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Iron-sulfur Cluster Deficiency, Pulmonary Hypertension, Friedreich Ataxia
- What is being tested?
- Right Heart Catheterization and Blood draw
- Type of treatment
- Surgery or procedure
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 1 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
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.
Read the 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:
- 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.
- Electrocardiogram.
- 6 Minute Walk Test.
- 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)
- 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:
- 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.
- ECG, done by research coordinator and read by PI/Sub-Investigator.
- 6 Minute Walk Test, done by research coordinator, if patient could perform.
- 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.
- Being tested
- Right Heart Catheterization, Blood draw
- Medical subject headings
- Hypertension, Pulmonary, Friedreich Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Right Heart CatheterizationProcedure or surgery
Some participants (i.e., those that are willing and able) will undergo a Right Heart Catheterization to check Cardiopulmonary function.
Blood drawOther
Test and control group will be asked to give 20 ml of blood samples
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 minute walk distance (meters)
In the TEST group, the investigators will measure 6 minute walk distance
Measured: 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.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study startOct 2015
- Primary completion1 Sep 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron-sulfur Cluster DeficiencyStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stephen Y. Chan, University of Pittsburgh
- Investigators
- Stephen Chan, MD, PhD, FAHA, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02594917
- Sponsor's protocol ID
- STUDY19030124
- Status last verified
- Sep 2023
- First submitted
- 29 Oct 2015
- Last updated
- 22 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT02594917
- Acronym / sponsor ID
- STUDY19030124
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Electrocardiogram.
- 6 Minute Walk Test.
- 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)
- 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:
- 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.
- ECG, done by research coordinator and read by PI/Sub-Investigator.
- 6 Minute Walk Test, done by research coordinator, if patient could perform.
- 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test Group | – | Procedure: Right Heart Catheterization, Other: Blood drawThe 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 | – | Other: Blood drawIt will also include ten additional patients (ages 18-60 yrs) who are unaffected first-degree family members of the above subjects. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Right Heart CatheterizationSome participants (i.e., those that are willing and able) will undergo a Right Heart Catheterization to check Cardiopulmonary function. | Procedure or surgery | Test Group |
| Blood drawTest and control group will be asked to give 20 ml of blood samples | Other | Control Group, Test Group |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Chan, MD, PhD, FAHA principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Iron-sulfur Cluster Deficiency and Pulmonary Hypertension, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 minute walk distance (meters) (time frame: baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2023.