Myocardial Perfusion Imaging Galmydar Rest/Stress

Development and Translation of Generator-Produced PET Tracer for Myocardial Perfusion Imaging

A single center, phase 0/1 clinical imaging study designed to assess the role of [68Ga]Galmydar PET/CT imaging in human subjects.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Ga-68 Galmydar; Drug: 13N-ammonia

Detailed Description

The primary objective of the proposed study is to evaluate the potential of [68Ga]Galmydar PET/CT MPI for the noninvasive detection of coronary artery disease. The study will evaluate [68Ga]Galmydar PET/CT MPI in comparison to [13N]ammonia PET/CT MPI to semi-quantitatively assess regional myocardial perfusion and quantitatively assess myocardial blood flow (MBF) in patients with suspected or known coronary artery disease (CAD) undergoing clinical SPECT MPI. In addition, perfusion and MBF findings with [68Ga]Galmydar will be compared to the results of coronary morphology or stenosis severity in those patients undergoing invasive coronary angiography (ICA) based on abnormal SPECT MPI. The performance of rest/stress [68Ga]Galmydar PET/CT in comparison to [13N]ammonia PET/CT in normal subjects without cardiovascular disease will be performed as a control. The primary objective of the proposed study is to evaluate the potential of [68Ga]Galmydar PET/CT MPI for the noninvasive detection of coronary artery disease. The study will evaluate [68Ga]Galmydar PET/CT MPI in comparison to [13N]ammonia PET/CT MPI in the same subjects to semi quantitatively assess regional myocardial perfusion and quantitatively assess myocardial blood flow (MBF) in patients with suspected or known coronary artery disease (CAD) undergoing clinical SPECT MPI. In addition, perfusion and MBF findings with [68Ga]Galmydar will be compared to the results of coronary morphology or stenosis severity in those patients undergoing invasive coronary angiography (ICA) based on abnormal SPECT MPI. The performance of rest/stress [68Ga]Galmydar PET/CT in comparison to [13N]ammonia PET/CT in normal subjects without cardiovascular disease will be performed as a control. Vital signs, serum chemistries, and serum blood counts will also be obtained.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dakkota m Thies; Phone Number: 314-747-3839; Email: d.thies@wustl.edu
• Study Contact Backup: Name: Kitty D Harrison, R.N; Phone Number: 314-747-0183; Email: kittydharrison@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Dakkota m Thies; Phone Number: 314-747-3839; Email: d.thies@wustl.edu
      • Contact: Kitty D Harrison, R.N; Phone Number: 314-747-0183; Email: kittydharrison@wustl.edu
      • Principal Investigator: Pamela K Woodard, M.D
      • Sub-Investigator: Thomas Schindler, MD, PHD
      • Sub-Investigator: Vijay Sharma, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female, 18-99 years of age and any race;
• Have had a prior clinical SPECT MPI positive for ischemia in two myocardial segments and referred for invasive coronary angiography (ICA) or have had a prior clinical SPECT MPI negative for ischemia;

Exclusion Criteria:

• Inability to receive and sign informed consent;
• Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6-months prior to SPECT or in the intervening days between SPECT and PET examination;
• Participants who have received chemotherapeutic agents within 6 months of enrollment;
• Heart failure (left ventricular ejection fraction ≤ 35%);
• Known non-ischemic cardiomyopathy;

• Inability to undergo pharmacologic stress testing with regadenoson (Lexiscan). Contraindications include:

  • Symptomatic bradycardia or second to third degree atrioventricular (AV) block;
  • Pre-existing obstructive lung disease with active wheezing, i.e., COPD, asthma with active wheezing that precludes the safe administration of the pharmacological stress agent according to the approved label;
  • Uncontrolled and severe hypertension (e.g. systolic blood pressure >200 mmHg, diastolic blood pressure >110 mmHg);
  • Baseline hypotension (e.g. systolic blood pressure < 90 mmHg, diastolic blood pressure <50 mmHg);
• Women who are pregnant or breastfeeding;
• Severe claustrophobia;
• Weight ≥ 500 lbs (weight limit of PET/CT table)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rest/ Stress imaging day 1; Participants will receive two [68Ga]Galmydar intravenous administrations, 4 mCi during rest and 8 mCi during stress for the PET MPI performed on Imaging Day-1.	Drug: Ga-68 Galmydar; Two intravenous injection of the PET radiotracer 68Ga-Galmydar.; Other Names: IND 157468
Experimental: rest/ stress imaging day 2; On Imaging Day-2, participants will receive two single administrations each of 10 mCi of 13N-Ammonia during the rest and stress PET MPI.	Drug: 13N-ammonia; Two intravenous Injection of PET radiotracer 13N-Ammonia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Semiquantitative assessment of 68Ga-Galmydar PET/CT uptake	Assessment of regional (17segment) myocardial uptake on 5-point scale (0 = normal; 4 = absent tracer uptake) per independent blind readout by 3 expert cardiac PET physicians.	Comparison to regional uptake on 13N-ammonia PET/CT performed 3-30 days after the 68Ga-Galmydar PET/CT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant change in respiratory rate.	A respiratory rate of < 12 or > 20 breaths/min.	6 hours from 68Ga-Galmydar injection
Clinically significant elevation in oral temperature	Oral temperature of >100 degrees F.	6 hours from 68Ga-Galmydar injection
Clinically significant change in serum chemistries: sodium, potassium, chloride, CO2	Serum chemistries (sodium, potassium, chloride, CO2) measured in mmol/L. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in serum chemistries: glucose, calcium creatinine, BUN, total bilirubin	Serum chemistries (glucose, calcium creatinine, BUN, total bilirubin), measured in mg/dL. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in serum chemistries: total protein, albumin.	Serum chemistries (total protein, albumin), measured in g/dL. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in serum chemistries: alkaline phosphatase, ALT, AST	Serum chemistries (alkaline phosphatase), measured in U/L. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in white blood cell count (WBC)	White blood cell count measured in WBC/mm3 blood. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in hemoglobin (Hgb)	Hgb measured in g/dL. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in hematocrit (Hct)	Hct measured in %. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in platelets	Platelets measured in platelets/mm3 blood. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in red blood cell count (RBC)	RBC measured in million/mm3. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Clinically significant change in mean corpuscular volume (MCV)	MCV measured in µm3. Values outside of laboratory range in comparison to baseline or >20% difference from baseline values.	6 hours from 68Ga-Galmydar injection
Assessment of myocardial blood flow on 68Ga-Galmydar PET/CT	Assessment of regional (17segment) myocardial blood flow (MBF) at stress and rest perfusion on 68Ga-Galmydar PET/CT.	Comparison to regional MBF on 13N-ammonia PET/CT performed 3-30 days after the 68Ga-Galmydar PET/CT
Change in systolic or diastolic blood pressure.	A 20 mmHg change from baseline in either systolic or diastolic blood pressure.	6 hours from 68Ga-Galmydar injection
Change in heart rate.	A 20 BPM change in heart rate from baseline.	6 hours from 68Ga-Galmydar injection
Number of patients with new AV Block	A change in EKG showing new AV Block (Type 1 or Type 2), Mobitz 2:1, or QTc ≥ 500ms).	6 hours from 68Ga-Galmydar injection
Number of patients with new bradycardia	New heart rate < 40 BPM on EKG.	6 hours from 68Ga-Galmydar injection

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Pamela K Woodard, M.D, Washington University School of Medicine

Publications and helpful links

General Publications

• Sivapackiam J, Laforest R, Sharma V. 68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents. Nucl Med Biol. 2018 Apr;59:29-35. doi: 10.1016/j.nucmedbio.2017.11.008. Epub 2017 Dec 1.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: November 13, 2022
• First Submitted That Met QC Criteria: November 20, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; Myocardial Blood Flow; Myocardial Perfusion imaging; Pharmacological Stress
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: 202107042-2; R01HL142297 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No