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Metabolic Imaging of the Heart Using Hyperpolarized (13C) Pyruvate Injection

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ClinicalTrials.gov Identifier: NCT02648009
Recruitment Status : Recruiting
First Posted : January 6, 2016
Last Update Posted : May 18, 2018
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Brief Summary:
The prevalence of congestive heart failure (CHF) in Canada is high, representing one of the health care system's most expensive diagnoses. Despite major advances in medicine, the mortality and morbidity from CHF remains great. Currently, magnetic resonance imaging (MRI) is used for non-invasive imaging of the cardiovascular system to enable the structure and anatomy of the organ to be visualized. However, current MRI methods have limitations when assessing and aiding in the management of CHF. A new imaging method has recently been developed that is showing great promise as a tool in the management of patients with CHF. Rapid imaging of biochemical reactions within myocytes using MRI has recently become possible through the use of the Dynamic Nuclear Polarization (DNP) and dissolution method. DNP-dissolution results in an intravenous contrast agent that is "hyperpolarized", producing a magnetic signal that is enhanced by up to 100,000 fold. The particular agent is carbon-13 labelled pyruvate. In this study, we demonstrate the first 13C-metabolic images of the human heart, along with the required hardware and data acquisition methods.

Condition or disease Intervention/treatment Phase
Hypertension Hypertrophy Drug: Hyperpolarized (13) Pyruvate Injection Phase 1

Detailed Description:

For this study, the heart of healthy subjects and those with hypertension or hypertrophy will be imaged using Hyperpolarized Pyruvate 13C Injection. Different forms of Hyperpolarized Pyruvate 13C Injection are available, with the 13C labelling at different positions within the molecule. These are equivalent from a safety perspective and covered by the same Investigators Brochure, but offer different metabolic information. Two different labelling patterns are investigated in this study. If images are successfully obtained, then insights into heart failure treatments that normalize the detrimental metabolic changes may enable earlier treatment and slow disease progression to CHF, ultimately reducing the high rates of morbidity and mortality associated with this disease.

Prior to enrolment, all participants will be screened in order to ensure they meet the study's inclusion and exclusion criteria and MRI eligibility. On the day of their scan, each participant will have an intravenous line inserted and receive a glucose drink, prior to scanning. The reason for this glucose drink is that a fed versus fasted state has been found to give markedly different measurements in animal models and a choice of meal would be a source of variability. The metabolic imaging will occur shortly after this drink.

For each scan, a 1.47 g sample of [1-13C]-pyruvic acid will be hyperpolarized using a SpinLab polarizer (General Electric Co.). The solid-state sample will be dissolved to a concentration of 250 mM pyruvate at biological pH. A 0.1 mmol/kg dose (approximately 20 mL) of this solution will be injected through an intravenous line, followed by a 25 mL saline flush. The 13C image acquisition will begin at the end of the injection and will record data during every heartbeat within the single breath-hold.

Heart rate and blood pressure will be monitored non-invasively, prior to the participant being positioned within the MR scanner. Heart rate will continue to be monitored during and after the scan and the participant will be monitored by the Study's Qualified Investigator or medical designate for up to 1 hour post injection.

The 13C imaging will be preceded by the standard cardiovascular MRI workup including breath-hold cine imaging to measure ejection fraction and LV mass (~30 minutes of scan time).

All clinical procedures will be completed at SHSC under the supervision of the Qualified Investigator, or medical designate.

Each participant will receive a follow up telephone call on the 7th day following the procedure to ascertain if any study related adverse events have occurred. The length of this study for participants is a single visit that will require approximately 3 hours of their time, except for participants in Groups 1C and 1F for whom the length for the study is two visits separated by at least 2 weeks, each requiring 3 hours. The entire study is expected to take about 3 years and the results should be known approximately six months after study completion.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Metabolic Imaging of the Heart Using Hyperpolarized (13C) Pyruvate Injection
Study Start Date : April 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Healthy Volunteers

Arm 1

  • Group 1A: healthy male volunteers between 19 and 50 years of age.
  • Group 1B: healthy female volunteers between 19 and 50 years of age.
  • Group 1C: healthy male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice
  • Group 1D: healthy male volunteers between 19 and 50 years of age.
  • Group 1E: healthy female volunteers between 19 and 50 years of age.
  • Group 1F: healthy male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice
Drug: Hyperpolarized (13) Pyruvate Injection
MRI with Hyperpolarized Pyruvate (13) Injection
Other Name: Hyperpolarized Pyruvate (13) Injection

Hypertension Hypertrophy Volunteers

Arm 2

  • Group 2A: patients aged 30 to 75 with hypertension and hypertrophy
  • Group 2B: patients aged 30 to 75 with non-obstructive hypertrophic cardiomyopathy (HCM).
  • Group 2C: stable outpatients with NYHA class 1-3 heart failure who have evidence of elevated LV mass (LVH).
  • Group 2D: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents.
  • Group 2E: patients aged 30 to 75 with hypertrophy
  • Group 2F: patients aged 30 to 75 with hypertrophic cardiomyopathy (HCM).
  • Group 2G: stable outpatients with NYHA class 1-3 heart failure who have evidence of elevated LV mass (LVH).
  • Group 2H: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents.
Drug: Hyperpolarized (13) Pyruvate Injection
MRI with Hyperpolarized Pyruvate (13) Injection
Other Name: Hyperpolarized Pyruvate (13) Injection




Primary Outcome Measures :
  1. Ability of the MRI machine to produce an image of the participant's heart following an injection of Hyperpolarized Pyruvate (13C) as assessed by the physician [ Time Frame: 2 years ]
    To demonstrate the first 13C-metabolic images of the human heart, along with the required hardware and data acquisition methods



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Written consent
  • Age: 19 to 50 in Arm 1, 30 to 75 in Arm 2
  • Group 2A and 2E participants have left-ventricular hypertrophy
  • Group 2B and 2F participants have diagnosed hypertrophic cardiomyopathy
  • Group 2C and 2G participants are stable outpatients with NYHA class 1-3 heart failure with evidence of elevated LV mass (LVH) and have idiopathic dilated cardiomyopathy
  • Group 2D and 2H participants are stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents

Exclusion Criteria

  • Contraindications to MRI or MRI contrast agents
  • Hemoglobin ≤ 9.0 gm/dL
  • Glomerular filtration rate (based on MDRD Equation) < 30 ml/min/1.73m2
  • Any condition leading to a life expectancy <1 year
  • Claustrophobia
  • Have received, or are scheduled to receive, another investigational medicinal product from 1 month prior to 1 month after inclusion in this study
  • BMI of less than 18.5 or greater than 32

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02648009


Contacts
Contact: Julie Green, MSc 4164806100 ext 83655 julie.green@sunnybrook.ca

Locations
Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Julie Green, MSc    4164896100 ext 83655    julie.green@sunnybrook.ca   
Principal Investigator: Charles Cunningham, PhD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
Principal Investigator: Charles Cunningham, PhD Sunnybrook Research Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT02648009     History of Changes
Other Study ID Numbers: 332-2014
First Posted: January 6, 2016    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
Hypertrophy
Pathological Conditions, Anatomical