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临床试验/NCT02648009
NCT02648009招募中1 期

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

Sunnybrook Health Sciences Centre2 个研究点 分布在 1 个国家目标入组 112 人开始时间: 2016年4月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
招募中
入组人数
112
试验地点
2
主要终点
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

研究概览

简要总结

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.

详细描述

For this study, the heart of control 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 enrollment, 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).

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Other
盲法
None

入排标准

年龄范围
19 Years 至 75 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 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), irrespective of LVEF.
  • Group 2D and 2H participants are stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents

排除标准

  • Contraindications to MRI or MRI contrast agents
  • Hemoglobin ≤ 9.0 gm/dL (only Group 2 participants)
  • Glomerular filtration rate (based on MDRD Equation) < 30 ml/min/1.73m2 (only Group 2 participants)
  • Any condition leading to a life expectancy <1 year
  • Medically diagnosed 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
  • Group 1: medically diagnosed heart disease

研究组 & 干预措施

Healthy Volunteers

Other

Arm 1

  • Group 1A: control male volunteers between 19 and 50 years of age.
  • Group 1B: control female volunteers between 19 and 50 years of age.
  • Group 1C: control male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice
  • Group 1D: control male volunteers between 19 and 50 years of age.
  • Group 1E: control female volunteers between 19 and 50 years of age.
  • Group 1F: control male or female volunteers between 19 and 50 years of age, with the MRI scan performed twice

干预措施: Hyperpolarized (13) Pyruvate Injection (Drug)

Hypertension Hypertrophy Volunteers

Other

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), irrespective of LVEF.
  • 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), irrespective of LVEF.
  • Group 2H: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents.

干预措施: Hyperpolarized (13) Pyruvate Injection (Drug)

Hypertension Hypertrophy Volunteers

Other

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), irrespective of LVEF.
  • 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), irrespective of LVEF.
  • Group 2H: stable patients with type 2 DM who have a HcA1c between 6.5-9% on oral hypoglycemic agents.

干预措施: Gadolinium (Drug)

结局指标

主要结局

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

时间窗: 2 years

To demonstrate the first 13C-metabolic images of the human heart, along with the required hardware and data acquisition methods

次要结局

  • Imaging of participant's heart with Gadolinium(2 years)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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