Pilot Study of Magnetic Resonance Imaging With Hyperpolarized Pyruvate (13C) In Patients With Fatty Liver Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Optimal pulse sequences (Part 1)
研究概览
简要总结
The recent development of dissolution dynamic nuclear polarization (DNP) technology for hyperpolarized (HP) 13C imaging offers a promising new avenue for non-invasively accessing fundamental metabolic changes associated with the progression of fatty liver disease in vivo. The purpose of this pilot study is to optimize sequence parameters for hyperpolarized 13C acquisition in the human liver and determine which metabolic changes can be seen in humans with simple, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) when compared to healthy volunteers.
详细描述
PRIMARY OBJECTIVES:
- Optimize scan parameters in order to maximize the signal-to-noise ratio of the HP 13C-pyruvate magnetic resonance imaging (MRI) in the liver.
- Determine whether the level of lactate production (as measured by the lactate/pyruvate ratio) in NASH participants, participants with simple NAFL, and healthy volunteers.
SECONDARY OBJECTIVES:
- Develop data analysis methods to quantify HP C-13 pyruvate MRI data.
- Further characterize the safety profile of HP C-13 pyruvate injections.
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1 (Imaging Optimization):
- •Able and willing to sign informed consent.
- •Age >= 18 years old at the time of study entry.
- •Part 2 (Pilot Study):
- •Group 1 (Fatty Liver Patients without NASH):
- •NAFL as determined by either clinical suspicion of fatty liver disease based on:
- •steatosis by imaging or histology,
- •no significant alcohol consumption,
- •absence of coexisting liver disease OR NAFL determined by liver biopsy 3 months prior to the scan, with the presence of fat on histology but absent ballooning or fibrosis. (nonalcoholic steatohepatitis activity score (NAS) <= 3).
- •Able and willing to sign informed consent.
- •Age ≥ 18 years old at the time of study entry.
- •Alcohol consumption < 2 drinks/day for men and <1 drink/day for women
- •Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody, human immunodeficiency virus (HIV) antibody negative.
- •Serum alanine aminotransferase (ALT) < 400 microliter (uL)
- •Group 2 (NASH Patients):
- •NASH as determined by liver biopsy 3 months prior to the scan.
- •a) NASH defined as NAS score greater than or equal to 4 with confirmation of NASH by an anatomic pathologist.
- •Able and willing to sign informed consent.
- •Age >= 18 years old at the time of study entry.
- •Alcohol consumption < 2 drinks/day for men and <1 drink/day for women
- •HBsAg, HCV antibody, HIV antibody negative.
- •Group 3 (Healthy volunteer):
- •No known history of diabetes or liver disease.
- •Able and willing to sign informed consent.
- •Age >= 18 years old at the time of study entry.
- •Body mass index <
- •Liver panel normal (aspartate aminotransferase (AST), ALT, alkaline phosphatase, bilirubin).
- •HBsAg, HCV antibody, HIV antibody negative.
- •Hemoglobin A1c < 5.7%.
- •Estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73m^2
排除标准
- •Part 1 (Imaging Optimization): For Cohorts 1/B only:
- •Poorly controlled hypertension, with blood pressure at study entry > 160 mmHg systolic or > 100 mmHg diastolic.
- •Congestive heart failure with New York Heart Association (NYHA) status ≥
- •Pregnant or nursing.
- •Participants unwilling or unable to undergo magnetic resonance (MR) imaging, including participants with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Participant size too large to fit in MR scanner.
- •Part 2 (Pilot Study): All groups
- •Poorly controlled hypertension, with blood pressure at study entry > 160 mmHg systolic or > 100 mmHg diastolic.
- •Current treatment with oral medication for diabetes.
- •Pregnant or nursing.
- •Participants unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Participant size too large to fit in MR scanner.
- •Congestive heart failure with New York Heart Association (NYHA) status >= 2.
研究组 & 干预措施
Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"
Participants will receive HP 13C injection, and receive an MRI scan. Imaging results will be used to optimize the hyperpolarized 13C part of the imaging procedure. Participants will also have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol", (up to a total of two injections per imaging visit separated by 15-60 minutes). Participants may be asked to fast up to 6 hours prior to the scan and the initial HP 13C MRI scan may be taken while participants are in a fasted state. Participants who have fasted will be offered up to 20 ounces (oz) of an oral glucose, fructose, or other high calorie drink (i.e. Gatorade, Coca-Cola, Ensure, etc.) to increase blood glucose levels, and a second HP 13C MRI scan will be performed after caloric intake.
干预措施: Hyperpolarized (HP) 13C (Drug)
Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"
Participants will receive HP 13C injection, and receive an MRI scan. Imaging results will be used to optimize the hyperpolarized 13C part of the imaging procedure. Participants will also have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol", (up to a total of two injections per imaging visit separated by 15-60 minutes). Participants may be asked to fast up to 6 hours prior to the scan and the initial HP 13C MRI scan may be taken while participants are in a fasted state. Participants who have fasted will be offered up to 20 ounces (oz) of an oral glucose, fructose, or other high calorie drink (i.e. Gatorade, Coca-Cola, Ensure, etc.) to increase blood glucose levels, and a second HP 13C MRI scan will be performed after caloric intake.
干预措施: Hyperpolarized 13C-Urea (Drug)
Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"
Participants will receive HP 13C injection, and receive an MRI scan. Imaging results will be used to optimize the hyperpolarized 13C part of the imaging procedure. Participants will also have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol", (up to a total of two injections per imaging visit separated by 15-60 minutes). Participants may be asked to fast up to 6 hours prior to the scan and the initial HP 13C MRI scan may be taken while participants are in a fasted state. Participants who have fasted will be offered up to 20 ounces (oz) of an oral glucose, fructose, or other high calorie drink (i.e. Gatorade, Coca-Cola, Ensure, etc.) to increase blood glucose levels, and a second HP 13C MRI scan will be performed after caloric intake.
干预措施: Magnetic Resonance Imaging (Procedure)
Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"
Participants will receive HP 13C injection, and receive an MRI scan. Imaging results will be used to optimize the hyperpolarized 13C part of the imaging procedure. Participants will also have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol", (up to a total of two injections per imaging visit separated by 15-60 minutes). Participants may be asked to fast up to 6 hours prior to the scan and the initial HP 13C MRI scan may be taken while participants are in a fasted state. Participants who have fasted will be offered up to 20 ounces (oz) of an oral glucose, fructose, or other high calorie drink (i.e. Gatorade, Coca-Cola, Ensure, etc.) to increase blood glucose levels, and a second HP 13C MRI scan will be performed after caloric intake.
干预措施: Saline Flush (Procedure)
Part 2 (Group 1): NAFLD
Participants with diagnosed NAFLD will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized (HP) 13C (Drug)
Part 2 (Group 1): NAFLD
Participants with diagnosed NAFLD will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized 13C-Urea (Drug)
Part 2 (Group 1): NAFLD
Participants with diagnosed NAFLD will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Magnetic Resonance Imaging (Procedure)
Part 2 (Group 2): NASH
Participants with diagnosed NASH will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized (HP) 13C (Drug)
Part 2 (Group 2): NASH
Participants with diagnosed NASH will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized 13C-Urea (Drug)
Part 2 (Group 2): NASH
Participants with diagnosed NASH will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Magnetic Resonance Imaging (Procedure)
Part 2 (Group 2): NASH
Participants with diagnosed NASH will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Saline Flush (Procedure)
Part 2 (Group 3): Healthy Volunteers
Healthy volunteers without known liver disease will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized (HP) 13C (Drug)
Part 2 (Group 3): Healthy Volunteers
Healthy volunteers without known liver disease will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Hyperpolarized 13C-Urea (Drug)
Part 2 (Group 3): Healthy Volunteers
Healthy volunteers without known liver disease will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Magnetic Resonance Imaging (Procedure)
Part 2 (Group 3): Healthy Volunteers
Healthy volunteers without known liver disease will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Saline Flush (Procedure)
Part 2 (Group 1): NAFLD
Participants with diagnosed NAFLD will receive HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" injection optimized in Part 1 of the study as well as standard liver MRI pulse sequences.
干预措施: Saline Flush (Procedure)
Part 1 (Cohort A): No injection of hyperpolarized (HP) 13C
Participants who are comprised of, primarily, healthy volunteers will undergo a standard MRI scan.
干预措施: Magnetic Resonance Imaging (Procedure)
结局指标
主要结局
Optimal pulse sequences (Part 1)
时间窗: 1 day
Establishing the pulse sequences for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
Signal-to-noise ratio (SNR) (Part 1, Cohort B)
时间窗: 1 day
SNR will be calculated..
Optimal respiratory parameter (Part 1)
时间窗: 1 day
Establishing the magnitude of respiratory motion for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
Mean lactate/pyruvate conversion rate (kPL) (Part 1, Cohort B)
时间窗: 1 day
Mean lactate-to-pyruvate conversion will be calculated with 95% confidence intervals.
Mean lactate-to-pyruvate ratio (Part 2)
时间窗: 1 day
The mean lactate-to-pyruvate ratio will be calculated for each of the diagnostic groups: (1) NAFL without steatohepatitis, (2) NASH, and (3) healthy volunteers.
Mean kPL(Part 2)
时间窗: 1 day
The mean kPL will be calculated for each of the diagnostic groups: (1) NAFL without steatohepatitis, (2) NASH, and (3) healthy volunteers.
Optimal coil placement (Part 1)
时间窗: 1 day
Establishing suitable radiofrequency (RF) coils for individual applications and proper use of MRI techniques such as parallel imaging to achieve optimal image quality will be conducted during the participant's scan. There is no formal analytic plan for Part 1 of the study, which is focused on optimizing the image acquisition protocol.
次要结局
未报告次要终点
研究者
Michael Ohliger, MD PhD
Principal Investigator
University of California, San Francisco