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New Heart Imaging Techniques to Evaluate Possible Heart Disease

Primary Purpose

Healthy, Obesity, Diabetes

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
MR Imaging Techniques - 1
MR Imaging Techniques - 2
MR Imaging Techniques - 3
MR Imaging Techniques - 4
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy focused on measuring Distensibility Imaging, Arteriosclerosis, Narrowing of Vessels, Endothelial Dysfunction, Hardening of the arteries, Non-Invasive Plaque Imaging, Cardiovascular Disease, Heart Disease, Arteriosclerosis, Healthy Volunteer, HV

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers
  • INCLUSION:

    1. Subjects with or without history of cardiovascular diseases and with various degrees of cardiovascular risk factor. Subjects with known or suspected atherosclerotic disease based on clinical findings or documented by angiography (conventional, CTA or MRA), or Doppler ultrasound. And, healthy volunteers and subjects with known or suspected diseases affecting the thoracic organs, abdominal organs, and other organs affected by metabolic diseases such as body fat and muscles. Subjects at risk for atherosclerosis including: smoking, obesity, hyperlipidemia, low levels of high density lipoproteins (<50 mg/dl for women and <40 mg/dl for men), hypertension, family history (early onset atherosclerosis <55 year old in male and < 65 year old in female who is first degree relative), and diabetes mellitus or metabolic syndrome.
    2. Subject must be willing to participate in the protocol.
    3. Subject age greater than 18 years old.
    4. Subject must be able to provide informed consent.
    5. Subject must be clinically stable and be able to come to the Clinical Center to participate in the study.

EXCLUSION CRITERIA:

  1. Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions:

    1. Implanted cardiac pacemaker or defibrillator
    2. Cochlear Implants
    3. Ocular foreign body (e.g. metal shavings)
    4. Embedded shrapnel fragments
    5. Central nervous system aneurysm clips
    6. Implanted neural stimulator
    7. Medical infusion pumps
    8. Any implanted device that is incompatible with MRI.
  2. Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and dyspnea at rest.
  3. Subjects requiring sedation for MRI studies.
  4. Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.).
  5. Pregnant or lactating women.
  6. Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination.
  7. Subjects who are unable to undergo a CTA within 2 months of the MRA part of this study, or are unable to undergo or be scheduled for a cardiac catheterization within 2 months of the MRA.

EXCLUSION CRITERIA - FOR GADOLINIUM BASED MRI STUDIES ONLY:

  1. History of allergic reaction to gadolinium contrast agents despite the use of premeditation with an anti-histaminic and cortisone.
  2. eGFR < 60 ml/min/1.73m^2

EXCLUSION CRITERIA - FOR CORONARY CTA:

  1. Contraindication to the use of CTA contrast agents:

    1. Creatinine value > 1.4 mg/dl
    2. History of multiple myeloma
    3. Use of metformin-containing products less than 24 hrs prior to contrast administration
    4. History of allergic reaction to CTA contrast agents despite the use of pre- medication with an anti-histaminic and cortisone.
  2. Subjects with contraindication precluding the use of beta blockers necessary to perform the coronary CTA. These include:

    1. Asthma
    2. Active bronchospasm
    3. Moderate or severe COPD
    4. 2nd or 3rd degree AV block
    5. Decompensated cardiac failure
    6. Allergy to beta blockers
    7. Systolic blood pressure < 100 mm Hg
    8. Pregnancy or nursing

EXCLUSION CRITERIA - FOR NITROGLYCERIN USE:

Subjects reporting a history of the following conditions will be excluded:

  1. Severe aortic stenosis
  2. Hypertrophic cardiomyopathy
  3. Inferior myocardial infarction with right ventricular involvement
  4. Cardiac tamponade
  5. Constrictive pericarditis
  6. Severe hypotension (systolic BP <90 mmHg)
  7. Uncorrected hypovolemia
  8. Raised intracranial pressure
  9. Glaucoma
  10. Severe anemia
  11. Concomitant use of phosphodiesterase-5 inhibitors (sildenafil-Viagra, tadalifil-Cialis, verdenafil-Levitra)
  12. History of hypersensitivity to nitroglycerin

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Group 4

Arm Description

Group 1 will consist of subjects with a 10-year total CHD risk <10% (low)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries

Group 2 will consist of subjects with a 10-year total CHD risk 10-20% (intermediate)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries

Group 3 will consist of subjects with a 10-year total CHD risk >20% (high)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries

Group 4 no known risk factors (control subjects)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries

Outcomes

Primary Outcome Measures

To develop and optimize clinical imaging protocols and techniques for fast high- resolution coronary MRA and wall imaging for the assessment of coronary and other main arteries structural distensibility, and endothelial functional parameters@...
The accelerated High-resolution MRA results will be compared to conventional angiography and/or computerized tomography angiography (CTA). High- resolution lumen dimensions will be compared to black- blood lumen measurements as well. It is expected that the MRA findings from the 3T scanner will demonstrate image quality that is nearly equivalent to the quality of the coronary arteries visualized using CTA and/or conventional coronary catheterization. Three- dimensional arterial dilatation mapping, representing endothelial function status, will be rendered and visualized
To evaluate early MR imagery signs of arterial structural, distensibility, and endothelial functional disorders associated with atherosclerosis in a cohort of patients with known or suspected coronary atherosclerosis
It is expected that the evaluation of the relationship among these risk factor and imaging variables will find relationships that can be further explored. This study is expected to find information in the data analysis that can be used to generate hypotheses for future testing.
To develop, implement, and optimize new non-invasive methods for characterization of the micro-environment in the thoracic and abdominal area utilizing specialized techniques
to develop, implement, and optimize new non-invasive methods for characterization of the micro-environment in the thoracic and abdominal area utilizing specialized techniques such as MR Spectroscopy, MR Elastography, and blood oxygenation level dependent (BOLD) imagingThe MRS, MRE and BOLD and other sequences results will be compared to conventional biopsy. It is expected that these advanced sequences will enable non-invasive evaluation and better understanding of various disease processes.

Secondary Outcome Measures

Full Information

First Posted
July 20, 2011
Last Updated
September 30, 2023
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01399385
Brief Title
New Heart Imaging Techniques to Evaluate Possible Heart Disease
Official Title
Magnetic Resonance of Body, Arterial Wall, and Angiography Imaging for Non- Invasive Assessment of Arterial Distensibility, Endothelial Dysfunction and Atherosclerotic Disease Using 1.5T and High Field (3T) MRI: A Technical Development Study of Cardiac and Body Imaging
Study Type
Interventional

2. Study Status

Record Verification Date
September 25, 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2011 (Actual)
Primary Completion Date
November 6, 2028 (Anticipated)
Study Completion Date
November 5, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: - Imaging tests, such as magnetic resonance imaging (MRI), can provide information about heart and blood vessels. The tests let doctors can see the amount of blood vessel narrowing and vessel wall thickness. This information may help diagnose and treat heart disease and other conditions that lead to heart attacks. Better MRI methods are needed to improve heart disease diagnosis, especially by avoiding the use of radiation. Researchers are testing new techniques to improve the quality of heart MRI, compared with more complex studies like catheterization or angiography. Objectives: - To compare heart MRI techniques with other tests used to diagnose heart disease. Eligibility: - People at least 18 years of age who either have or may have heart disease, or are healthy volunteers. Design: Participants will be screened with a physical exam, medical history, and blood tests. They will have an angiography to study the inside of blood vessels. This test is an x-ray study of the blood vessels. It will be done either separately or as part of a set of tests to diagnose possible heart disease. Participants will have at least one and up to five MRI scans. The scans will involve different methods of studying the heart and blood vessels. Participants may also have a computed tomography scan to confirm the findings of an MRI scan. No treatment will be provided as part of this protocol.
Detailed Description
Specialized imaging techniques now available allow a unique opportunity to characterize the micro-environment of the human body. Magnetic Resonance (MR) vascular wall imaging and angiography (MRA) are developing techniques that permit non-invasive evaluation of arterial and venous structures without the need for x-ray based catheter angiography. In addition, vessel wall imaging provides unprecedented non-invasive tools to assess vascular endothelial function. While dramatic progress has been made to cardiovascular MR imaging in the last few years, there are still substantial limitations in the resolution, accuracy, and reproducibility of MRA and wall imaging in the comprehensive structural and functional evaluation of coronary artery. The first aim of this study is to develop and optimize clinical imaging protocols and techniques for fast high-resolution coronary MRA and wall imaging for the assessment of coronary and other main arteries structural, distensibility, and endothelial functional parameters. Technique optimization and performance evaluation will be accomplished in normal subjects without known or suspected coronary atherosclerosis. The second aim of this protocol is to evaluate early MR imagery signs of arterial structural, distensibility, and endothelial functional disorders associated with atherosclerosis in a cohort of patients with known or suspected coronary atherosclerosis. Results from accelerated high-resolution MRA will be correlated with corresponding Computerized Tomography Coronary Angiogram (CTA) results. The third aim of this protocol is to develop, implement, and optimize new non-invasive methods for characterization of the micro-environment in the thoracic and abdominal area utilizing specialized techniques such as MR Spectroscopy, MR Elastography, and blood oxygenation level dependent (BOLD) imaging. The long-term objective of this study and research initiative is to optimize coronary MRA, wall, and body imaging techniques to the point that it can reliably be used for routine prevention and assessment of early atherosclerosis and other diseases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Obesity, Diabetes, Healthy Volunteers, Atherosclerosis
Keywords
Distensibility Imaging, Arteriosclerosis, Narrowing of Vessels, Endothelial Dysfunction, Hardening of the arteries, Non-Invasive Plaque Imaging, Cardiovascular Disease, Heart Disease, Arteriosclerosis, Healthy Volunteer, HV

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Group 1 will consist of subjects with a 10-year total CHD risk <10% (low)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Group 2 will consist of subjects with a 10-year total CHD risk 10-20% (intermediate)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Group 3 will consist of subjects with a 10-year total CHD risk >20% (high)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Group 4 no known risk factors (control subjects)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Intervention Type
Device
Intervention Name(s)
MR Imaging Techniques - 1
Intervention Description
Group 1 will consist of subjects with a 10-year total CHD risk <10% (low)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Intervention Type
Device
Intervention Name(s)
MR Imaging Techniques - 2
Intervention Description
Group 2 will consist of subjects with a 10-year total CHD risk 10-20% (intermediate)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Intervention Type
Device
Intervention Name(s)
MR Imaging Techniques - 3
Intervention Description
Group 3 will consist of subjects with a 10-year total CHD risk >20% (high)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Intervention Type
Device
Intervention Name(s)
MR Imaging Techniques - 4
Intervention Description
Group 4 no known risk factors (control subjects)They will undergo a series of multiple small discovery studies in order to look at the multiple different MR methods of visualizing the coronary arteries
Primary Outcome Measure Information:
Title
To develop and optimize clinical imaging protocols and techniques for fast high- resolution coronary MRA and wall imaging for the assessment of coronary and other main arteries structural distensibility, and endothelial functional parameters@...
Description
The accelerated High-resolution MRA results will be compared to conventional angiography and/or computerized tomography angiography (CTA). High- resolution lumen dimensions will be compared to black- blood lumen measurements as well. It is expected that the MRA findings from the 3T scanner will demonstrate image quality that is nearly equivalent to the quality of the coronary arteries visualized using CTA and/or conventional coronary catheterization. Three- dimensional arterial dilatation mapping, representing endothelial function status, will be rendered and visualized
Time Frame
within one month
Title
To evaluate early MR imagery signs of arterial structural, distensibility, and endothelial functional disorders associated with atherosclerosis in a cohort of patients with known or suspected coronary atherosclerosis
Description
It is expected that the evaluation of the relationship among these risk factor and imaging variables will find relationships that can be further explored. This study is expected to find information in the data analysis that can be used to generate hypotheses for future testing.
Time Frame
within one month
Title
To develop, implement, and optimize new non-invasive methods for characterization of the micro-environment in the thoracic and abdominal area utilizing specialized techniques
Description
to develop, implement, and optimize new non-invasive methods for characterization of the micro-environment in the thoracic and abdominal area utilizing specialized techniques such as MR Spectroscopy, MR Elastography, and blood oxygenation level dependent (BOLD) imagingThe MRS, MRE and BOLD and other sequences results will be compared to conventional biopsy. It is expected that these advanced sequences will enable non-invasive evaluation and better understanding of various disease processes.
Time Frame
within one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION: Subjects with or without history of cardiovascular diseases and with various degrees of cardiovascular risk factor. Subjects with known or suspected atherosclerotic disease based on clinical findings or documented by angiography (conventional, CTA or MRA), or Doppler ultrasound. And, healthy volunteers and subjects with known or suspected diseases affecting the thoracic organs, abdominal organs, and other organs affected by metabolic diseases such as body fat and muscles. Subjects at risk for atherosclerosis including: smoking, obesity, hyperlipidemia, low levels of high density lipoproteins (<50 mg/dl for women and <40 mg/dl for men), hypertension, family history (early onset atherosclerosis <55 year old in male and < 65 year old in female who is first degree relative), and diabetes mellitus or metabolic syndrome. Subject must be willing to participate in the protocol. Subject age greater than 18 years old. Subject must be able to provide informed consent. Subject must be clinically stable and be able to come to the Clinical Center to participate in the study. EXCLUSION CRITERIA: Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions: Implanted cardiac pacemaker or defibrillator Cochlear Implants Ocular foreign body (e.g. metal shavings) Embedded shrapnel fragments Central nervous system aneurysm clips Implanted neural stimulator Medical infusion pumps Any implanted device that is incompatible with MRI. Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and dyspnea at rest. Subjects requiring sedation for MRI studies. Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.). Pregnant or lactating women. Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination. Subjects who are unable to undergo a CTA within 2 months of the MRA part of this study, or are unable to undergo or be scheduled for a cardiac catheterization within 2 months of the MRA. EXCLUSION CRITERIA - FOR GADOLINIUM BASED MRI STUDIES ONLY: History of allergic reaction to gadolinium contrast agents despite the use of premeditation with an anti-histaminic and cortisone. eGFR < 60 ml/min/1.73m^2 EXCLUSION CRITERIA - FOR CORONARY CTA: Contraindication to the use of CTA contrast agents: Creatinine value > 1.4 mg/dl History of multiple myeloma Use of metformin-containing products less than 24 hrs prior to contrast administration History of allergic reaction to CTA contrast agents despite the use of pre- medication with an anti-histaminic and cortisone. Subjects with contraindication precluding the use of beta blockers necessary to perform the coronary CTA. These include: Asthma Active bronchospasm Moderate or severe COPD 2nd or 3rd degree AV block Decompensated cardiac failure Allergy to beta blockers Systolic blood pressure < 100 mm Hg Pregnancy or nursing EXCLUSION CRITERIA - FOR NITROGLYCERIN USE: Subjects reporting a history of the following conditions will be excluded: Severe aortic stenosis Hypertrophic cardiomyopathy Inferior myocardial infarction with right ventricular involvement Cardiac tamponade Constrictive pericarditis Severe hypotension (systolic BP <90 mmHg) Uncorrected hypovolemia Raised intracranial pressure Glaucoma Severe anemia Concomitant use of phosphodiesterase-5 inhibitors (sildenafil-Viagra, tadalifil-Cialis, verdenafil-Levitra) History of hypersensitivity to nitroglycerin
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jatin R Matta, P.A.-C
Phone
(301) 443-8373
Email
mattaj@mail.nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Ahmed M Gharib, M.D.
Phone
(301) 402-5744
Email
agharib@mail.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmed M Gharib, M.D.
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
11684624
Citation
Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001 Oct 30;104(18):2158-63. doi: 10.1161/hc4301.098254.
Results Reference
background
PubMed Identifier
1175657
Citation
Bradbury EM, Chapman GE, Danby SE, Hartman PG, Riches PL. Studies on the role and mode of operation of the very-lysine-rich histone H1 (F1) in eukaryote chromatin. The properties of the N-terminal and C-terminal halves of histone H1. Eur J Biochem. 1975 Sep 15;57(2):521-8. doi: 10.1111/j.1432-1033.1975.tb02327.x.
Results Reference
background
PubMed Identifier
9809543
Citation
Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med. 1998 Nov;4(11):1241-3. doi: 10.1038/3218. No abstract available.
Results Reference
background
PubMed Identifier
33724063
Citation
Ouwerkerk R, Hamimi A, Matta J, Abd-Elmoniem KZ, Eary JF, Abdul Sater Z, Chen KY, Cypess AM, Gharib AM. Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids. Radiology. 2021 May;299(2):396-406. doi: 10.1148/radiol.2021202676. Epub 2021 Mar 16.
Results Reference
derived
PubMed Identifier
29617001
Citation
Muniyappa R, Noureldin RA, Abd-Elmoniem KZ, El Khouli RH, Matta JR, Hamimi A, Ranganath S, Hadigan C, Nieman LK, Gharib AM. Personalized Statin Therapy and Coronary Atherosclerotic Plaque Burden in Asymptomatic Low/Intermediate-Risk Individuals. Cardiorenal Med. 2018;8(2):140-150. doi: 10.1159/000487205. Epub 2018 Mar 26.
Results Reference
derived
PubMed Identifier
23559084
Citation
Neary NM, Booker OJ, Abel BS, Matta JR, Muldoon N, Sinaii N, Pettigrew RI, Nieman LK, Gharib AM. Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab. 2013 May;98(5):2045-52. doi: 10.1210/jc.2012-3754. Epub 2013 Apr 4.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2011-DK-0168.html
Description
NIH Clinical Center Detailed Web Page

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New Heart Imaging Techniques to Evaluate Possible Heart Disease

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