3D PET Myocardial Blood Flow and Rb82 Infusion Profiles

NCT ID: NCT05286593

Last Updated: 2023-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-28

Study Completion Date

2022-09-30

Brief Summary

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The investigators seek to test bolus infusions (50ml/min) vs. slow infusions (20 ml/min) of Rb-82 on metrics of coronary blood flow assessed on a modern 3D PET/CT.

Detailed Description

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As perfusion metrics in the healthy volunteers, patients with risk factors and/or coronary artery disease and in tissue with transmural myocardial infarctions has been well defined AND same day test-retest variability minutes apart using a bolus infusion is ±10%, the investigators shall test 3 hypotheses. The first hypothesis is repeated same day test-retest coefficient of variation (COV) of whole heart rMBF and sMBF acquired using a bolus infusion profile (50 mls/min) on a modern 3D PET scanner falls within ± 10%. The second hypothesis is repeated same day test-retest COV of whole heart rMBF and sMBF acquired using a slow infusion activity profile (20 mls/min) on a modern 3D PET scanner falls within ± 10%. The third hypothesis is COV of whole heart rMBF and sMBF between bolus and slow activity profiles is ± 10% where the bolus is considered the standard on a modern 3D PET scanner.

The investigators will test the different activity profiles on 3 distinct populations:

1. Healthy volunteers
2. Clinical volunteers with risk factors and/or CAD
3. Volunteers with clinical infarcts.

Conditions

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Normal Healthy Volunteers Without Chronic Medical Conditions Coronary Artery Disease Cardiac Risk Factors Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

All participants will receive a standard "high flow rate" weight based bolus of Rb-82 and a "low flow rate" weight based infusion of Rb-82. The bolus and infusion doses will be administered randomly at rest and stress however the bolus is considered the gold standard.

In addition, under resting conditions, participants will also receive a third dose of Rb-82 that is either a bolus or low flow rate (assigned randomly).
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Normal volunteers

Normal participants will receive serial doses of Rb-82 administered as either a bolus (B) (gold standard) or slow infusion (SI). Under resting conditions, they will receive 3 weight based doses. The first two doses are randomly assigned B and SI. The third dose is either B or SI. Under stress conditions, they will receive 2 weight based doses that are randomly assigned B and SI.

Group Type OTHER

Slow Infusion of Rubidium-82

Intervention Type DRUG

Normal volunteers will receive weight based doses of Rb-82 infused as a slow infusion

Clinical patients

Clinical patients participants will receive serial doses of Rb-82 administered as either a bolus (B) (gold standard) or slow infusion (SI). Under resting conditions, they will receive 3 weight based doses. The first two doses are randomly assigned B and SI. The third dose is either B or SI. Under stress conditions, they will receive 2 weight based doses that are randomly assigned B and SI.

Group Type OTHER

Slow Infusion of Rubidium-82

Intervention Type DRUG

Clinical patients will receive weight based doses of Rb-82 infused as a slow infusion

Infarcts

Infarct participants will receive serial doses of Rb-82 administered as either a bolus (B) (gold standard) or slow infusion (SI). Under resting conditions, they will receive 3 weight based doses. The first two doses are randomly assigned B and SI. The third dose is either B or SI. Under stress conditions, they will receive 2 weight based doses that are randomly assigned B and SI.

Group Type OTHER

Slow Infusion of Rubidium-82

Intervention Type DRUG

Infarct volunteers will receive weight based doses of Rb-82 infused as a slow infusion

Interventions

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Slow Infusion of Rubidium-82

Normal volunteers will receive weight based doses of Rb-82 infused as a slow infusion

Intervention Type DRUG

Slow Infusion of Rubidium-82

Clinical patients will receive weight based doses of Rb-82 infused as a slow infusion

Intervention Type DRUG

Slow Infusion of Rubidium-82

Infarct volunteers will receive weight based doses of Rb-82 infused as a slow infusion

Intervention Type DRUG

Other Intervention Names

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20 mls/min of Rubidium-82 20 mls/min of Rubidium-82 20 mls/min of Rubidium-82

Eligibility Criteria

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Inclusion Criteria

Normal Volunteers

* Adults ≥18 and \<40 years old able to give informed consent.
* Ability to abstain from caffeine for 48 hours

The "clinical" population

* Adults ≥18 years old able to give informed consent.
* Any cardiac risk factor including hypertension, hyperlipidemia, diabetes mellitus or tobacco use OR
* CAD defined by with history of PCI or CABG, Coronary Ca score\>400, or dense coronary calcifications noted on chest CT
* Ability to abstain from caffeine for 48 hours

The "infarct" population

* Adults ≥18 years old able to give informed consent.
* Prior cardiac PET scan demonstrating a fixed defect ≥ 15% of the LV myocardium with relative uptake ≤60% maximum uptake.
* In addition, to the perfusion defect, each volunteer requires either:

* FDG PET or MRI viability studies confirming infarct OR
* akinesis and wall thinning on ECHO within the same territory as the PET defect in addition to Q-waves on ECG
* Ability to abstain from caffeine for 48 hours

Exclusion Criteria

Normal Volunteers

* Any chronic cardiac disease or condition (e.g., hypertension, hyperlipidemia)
* Any chronic systemic disease or condition (e.g., diabetes, systemic lupus, rheumatoid arthritis)
* Tobacco use
* Family history in a first degree relative with clinical CAD (h/o PCI, MI or CABG) in men \<55 or women \<65
* Severe claustrophobia
* Positive urine pregnancy test
* Inability to give informed consent
* BMI ≥ 30 or BMI\>25 and \<30 provided waist to hip ratio \>0.80 in women or 0.90 in men.

The "clinical" and "infarct" populations

* Severe claustrophobia
* Hemodynamic instability or unstable symptoms
* Positive urine pregnancy test
* Inability to give informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bracco Corporate

INDUSTRY

Sponsor Role collaborator

Ochsner Health System

OTHER

Sponsor Role lead

Responsible Party

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Robert Bober, M.D.

Director of Nuclear Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ochsner

New Orleans, Louisiana, United States

Site Status

Countries

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United States

References

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Araujo LI, Lammertsma AA, Rhodes CG, McFalls EO, Iida H, Rechavia E, Galassi A, De Silva R, Jones T, Maseri A. Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation. 1991 Mar;83(3):875-85. doi: 10.1161/01.cir.83.3.875.

Reference Type BACKGROUND
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Bergmann SR, Fox KA, Rand AL, McElvany KD, Welch MJ, Markham J, Sobel BE. Quantification of regional myocardial blood flow in vivo with H215O. Circulation. 1984 Oct;70(4):724-33. doi: 10.1161/01.cir.70.4.724.

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Sdringola S, Johnson NP, Kirkeeide RL, Cid E, Gould KL. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. JACC Cardiovasc Imaging. 2011 Apr;4(4):402-12. doi: 10.1016/j.jcmg.2011.02.008.

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Renaud JM, DaSilva JN, Beanlands RS, DeKemp RA. Characterizing the normal range of myocardial blood flow with (8)(2)rubidium and (1)(3)N-ammonia PET imaging. J Nucl Cardiol. 2013 Aug;20(4):578-91. doi: 10.1007/s12350-013-9721-3. Epub 2013 May 9.

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Kern MJ, Bach RG, Mechem CJ, Caracciolo EA, Aguirre FV, Miller LW, Donohue TJ. Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease. J Am Coll Cardiol. 1996 Nov 1;28(5):1154-60. doi: 10.1016/S0735-1097(96)00327-0.

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PMID: 8890809 (View on PubMed)

Gewirtz H, Fischman AJ, Abraham S, Gilson M, Strauss HW, Alpert NM. Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction. J Am Coll Cardiol. 1994 Mar 15;23(4):851-9. doi: 10.1016/0735-1097(94)90629-7.

Reference Type BACKGROUND
PMID: 8106689 (View on PubMed)

Rivas F, Cobb FR, Bache RJ, Greenfield JC Jr. Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs. Circ Res. 1976 May;38(5):439-47. doi: 10.1161/01.res.38.5.439.

Reference Type BACKGROUND
PMID: 1269083 (View on PubMed)

Kitkungvan D, Johnson NP, Roby AE, Patel MB, Kirkeeide R, Gould KL. Routine Clinical Quantitative Rest Stress Myocardial Perfusion for Managing Coronary Artery Disease: Clinical Relevance of Test-Retest Variability. JACC Cardiovasc Imaging. 2017 May;10(5):565-577. doi: 10.1016/j.jcmg.2016.09.019. Epub 2016 Dec 21.

Reference Type BACKGROUND
PMID: 28017383 (View on PubMed)

Murthy VL, Bateman TM, Beanlands RS, Berman DS, Borges-Neto S, Chareonthaitawee P, Cerqueira MD, deKemp RA, DePuey EG, Dilsizian V, Dorbala S, Ficaro EP, Garcia EV, Gewirtz H, Heller GV, Lewin HC, Malhotra S, Mann A, Ruddy TD, Schindler TH, Schwartz RG, Slomka PJ, Soman P, Di Carli MF, Einstein A, Russell R, Corbett JR. Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC. J Nucl Cardiol. 2018 Feb;25(1):269-297. doi: 10.1007/s12350-017-1110-x. No abstract available.

Reference Type BACKGROUND
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Renaud JM, Yip K, Guimond J, Trottier M, Pibarot P, Turcotte E, Maguire C, Lalonde L, Gulenchyn K, Farncombe T, Wisenberg G, Moody J, Lee B, Port SC, Turkington TG, Beanlands RS, deKemp RA. Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow. J Nucl Med. 2017 Jan;58(1):103-109. doi: 10.2967/jnumed.116.174565. Epub 2016 Aug 18.

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Bui L, Kitkungvan D, Roby AE, Nguyen TT, Gould KL. Pitfalls in quantitative myocardial PET perfusion II: Arterial input function. J Nucl Cardiol. 2020 Apr;27(2):397-409. doi: 10.1007/s12350-020-02074-8. Epub 2020 Mar 3.

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Gould KL, Bui L, Kitkungvan D, Patel MB. Reliability and Reproducibility of Absolute Myocardial Blood Flow: Does It Depend on the PET/CT Technology, the Vasodilator, and/or the Software? Curr Cardiol Rep. 2021 Jan 22;23(3):12. doi: 10.1007/s11886-021-01449-8.

Reference Type BACKGROUND
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Bober RM, Milani RV, Kachur SM, Morin DP. Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography. EJNMMI Res. 2023 Sep 27;13(1):87. doi: 10.1186/s13550-023-01037-7.

Reference Type DERIVED
PMID: 37752344 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://doi.org/10.17996/anc.21-00137

Quantification of Resting Myocardial Blood Flow Using Rubidum82 Positron Emission Tomography in Regions with MRI-Confirmed Myocardial Scar. Annals of Nuclear Cardiology.

Other Identifiers

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STUDY00001584

Identifier Type: -

Identifier Source: org_study_id

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