Hyperpolarized Pyruvate (13C) Magnetic Resonance Imaging In Patients With Fatty Liver Disease

NCT06176079 | Unknown FDA Drug

• 2 other identifiers: 19-293815R01DK115987
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Fatty Liver; Non Alcoholic Steatohepatitis; NAFLD; NASH

Outcome Measures

Primary Outcomes (7)

• Optimal coil placement (Part 1)

  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.

  1 day

• Optimal pulse sequences (Part 1)

  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.

  1 day

• Optimal respiratory parameter (Part 1)

  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.

  1 day

• Mean lactate/pyruvate conversion rate (kPL) (Part 1, Cohort B)

  Mean lactate-to-pyruvate conversion will be calculated with 95% confidence intervals.

  1 day

• Signal-to-noise ratio (SNR) (Part 1, Cohort B)

  SNR will be calculated..

  1 day

• Mean lactate-to-pyruvate ratio (Part 2)

  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.

  1 day

• Mean kPL(Part 2)

  The mean kPL will be calculated for each of the diagnostic groups: (1) NAFL without steatohepatitis, (2) NASH, and (3) healthy volunteers.

  1 day

Study Arms (5)

Part 1 (Cohort A): No injection of hyperpolarized (HP) 13C

Participants who are comprised of, primarily, healthy volunteers will undergo a standard MRI scan.

Procedure: Magnetic Resonance Imaging

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.

Drug: Hyperpolarized (HP) 13C; Drug: Hyperpolarized 13C-Urea; Procedure: Magnetic Resonance Imaging; Procedure: Saline Flush

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.

Drug: Hyperpolarized (HP) 13C; Drug: Hyperpolarized 13C-Urea; Procedure: Magnetic Resonance Imaging; Procedure: Saline Flush

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.

Drug: Hyperpolarized (HP) 13C; Drug: Hyperpolarized 13C-Urea; Procedure: Magnetic Resonance Imaging; Procedure: Saline Flush

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.

Drug: Hyperpolarized (HP) 13C; Drug: Hyperpolarized 13C-Urea; Procedure: Magnetic Resonance Imaging; Procedure: Saline Flush

Interventions

Hyperpolarized (HP) 13C DRUG

A dosage of 0.43 mL/kg body weight at the maximum dosage will be injected intravenously at a rate of 5 mL/second.

Also known as: HP 13C

Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"; Part 2 (Group 1): NAFLD; Part 2 (Group 2): NASH; Part 2 (Group 3): Healthy Volunteers

Hyperpolarized 13C-Urea DRUG

Given intravenously (IV)

Also known as: HP13C-urea, copol

Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"; Part 2 (Group 1): NAFLD; Part 2 (Group 2): NASH; Part 2 (Group 3): Healthy Volunteers

Magnetic Resonance Imaging PROCEDURE

Imaging procedure

Also known as: MRI, MR

Part 1 (Cohort A): No injection of hyperpolarized (HP) 13C; Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"; Part 2 (Group 1): NAFLD; Part 2 (Group 2): NASH; Part 2 (Group 3): Healthy Volunteers

Saline Flush PROCEDURE

A 20 milliliter (mL) saline flush at 5 mL/second will be given after each dose of HP 13C

Part 1 (Cohort B): Injection of hyperpolarized (HP) 13C or HP13C-pyruvate+HP13C-urea "copol"; Part 2 (Group 1): NAFLD; Part 2 (Group 2): NASH; Part 2 (Group 3): Healthy Volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients with diagnosed NASH or NAFLD, or adult healthy volunteers.

You may qualify if:

• 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):

You may not qualify if:

• 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 ≥ 2.
• 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.

Sponsors & Collaborators

• Michael Ohliger, MD PhD: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be obtained.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Michael Ohliger, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Louise Magat

CONTACT

(415) 502-1822; Louise.Magat@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 10, 2023
• First Posted: December 19, 2023
• Study Start: July 22, 2020
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)