Clinical trial NCT06176079: Hyperpolarized Pyruvate (13C) Magnetic Resonance Imaging In Patients With Fatty Liver Disease
Official title: Pilot Study of Magnetic Resonance Imaging With Hyperpolarized Pyruvate (13C) In Patients With Fatty Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-Alcoholic Fatty Liver Disease
Non Alcoholic Fatty Liver
Non Alcoholic Steatohepatitis
NAFLD
NASH
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-12-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with diagnosed NASH or NAFLD, or adult healthy volunteers.

Brief summary: 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.

Detailed description: PRIMARY OBJECTIVES:

1. Optimize scan parameters in order to maximize the signal-to-noise ratio of the HP 13C-pyruvate magnetic resonance imaging (MRI) in the liver.
2. 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:

1. Develop data analysis methods to quantify HP C-13 pyruvate MRI data.
2. Further characterize the safety profile of HP C-13 pyruvate injections.

EXPLORATORY OBJECTIVES:

1. Examine the impact of the dual liver blood supply on the vascular kinetics of observed hyperpolarized 13C metabolism.
2. Improve methods of quantification and motion correction for hyperpolarized 13C acquisition, incorporating perfusion information derived from 13C Urea

OUTLINE:

Part 1: (Imaging Optimization, N=50): Participants enrolled in Part 1 will predominantly be healthy volunteers. As the protocol optimization is completed, there is a possibility that testing in using data from participants with fatty liver disease may be performed. Participants in this part will be divided into two cohorts:

* Cohort A: Participants will undergo MRI but no injection of hyperpolarized 13C.
* Cohort B: Participants will receive one HP 13C injection. Participants in this cohort will have the option of undergoing repeated dose imaging studies of HP 13C-pyruvate or HP 13C-pyruvate+HP 13C-urea "copol", for up to a total of two injections per imaging visit.

Part 2: (Pilot Study, N=30): Participants enrolled in Part 2 will receive the HP 13C-pyruvate or HP13C-pyruvate+HP13C-urea "copol" protocol that was optimized in Part 1 as well as standard liver MRI pulse sequences. Participants will be stratified into the following groups based on diagnosis:

* Group 1 (n=10): Participants with a diagnosis of non-alcoholic fatty liver without steatohepatitis (NAFL)
* Group 2 (n=10): Participants with a diagnosis of non-alcoholic steatohepatitis (NASH)
* Group 3 (n=10): Participants with no known liver disease (healthy volunteers)

Participants will be followed for 2-4 days following imaging procedure.

Eligibility criteria: Inclusion Criteria:

Part 1 (Imaging Optimization):

1. Able and willing to sign informed consent.
2. Age \>= 18 years old at the time of study entry.

Part 2 (Pilot Study):

* Group 1 (Fatty Liver Patients without NASH):

  1. NAFL as determined by either clinical suspicion of fatty liver disease based on:

     1. steatosis by imaging or histology,
     2. no significant alcohol consumption,
     3. 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).
  2. Able and willing to sign informed consent.
  3. Age ≥ 18 years old at the time of study entry.
  4. Alcohol consumption \< 2 drinks/day for men and \<1 drink/day for women
  5. Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) antibody, human immunodeficiency virus (HIV) antibody negative.
  6. Serum alanine aminotransferase (ALT) \< 400 microliter (uL)
* Group 2 (NASH Patients):

  1. 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.
  2. Able and willing to sign informed consent.
  3. Age \>= 18 years old at the time of study entry.
  4. Alcohol consumption \< 2 drinks/day for men and \<1 drink/day for women
  5. HBsAg, HCV antibody, HIV antibody negative.
* Group 3 (Healthy volunteer):

  1. No known history of diabetes or liver disease.
  2. Able and willing to sign informed consent.
  3. Age \>= 18 years old at the time of study entry.
  4. Body mass index \< 25.
  5. Liver panel normal (aspartate aminotransferase (AST), ALT, alkaline phosphatase, bilirubin).
  6. HBsAg, HCV antibody, HIV antibody negative.
  7. Hemoglobin A1c \< 5.7%.
  8. Estimated glomerular filtration rate (eGFR) \>= 60 mL/min/1.73m\^2

Exclusion Criteria:

Part 1 (Imaging Optimization): For Cohorts 1/B only:

1. Poorly controlled hypertension, with blood pressure at study entry \> 160 mmHg systolic or \> 100 mmHg diastolic.
2. Congestive heart failure with New York Heart Association (NYHA) status ≥ 2.
3. Pregnant or nursing.
4. 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.
5. Participant size too large to fit in MR scanner.

Part 2 (Pilot Study): All groups

1. Poorly controlled hypertension, with blood pressure at study entry \> 160 mmHg systolic or \> 100 mmHg diastolic.
2. Current treatment with oral medication for diabetes.
3. Pregnant or nursing.
4. 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.
5. Participant size too large to fit in MR scanner.
6. Congestive heart failure with New York Heart Association (NYHA) status \>= 2.

Primary outcomes:
measure: Optimal coil placement (Part 1)
timeFrame: 1 day
measure: Optimal pulse sequences (Part 1)
timeFrame: 1 day
measure: Optimal respiratory parameter (Part 1)
timeFrame: 1 day
measure: Mean lactate/pyruvate conversion rate (kPL) (Part 1, Cohort B)
timeFrame: 1 day
measure: Signal-to-noise ratio (SNR) (Part 1, Cohort B)
timeFrame: 1 day
measure: Mean lactate-to-pyruvate ratio (Part 2)
timeFrame: 1 day
measure: Mean kPL(Part 2)
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Michael Ohliger, MD
role: PRINCIPAL_INVESTIGATOR
References: