Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway (HPFFF)

February 17, 2025 updated by: Craig Riggs Malloy, University of Texas Southwestern Medical Center

Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway (HP FFF)

The investigators plan to evaluate sensitivity and specificity of HP 13C-pyruvate as an imaging agent for detection of altered PDH flux in fatty liver.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators plan to determine whether nutritional state and fatty liver influence the production of [13C]bicarbonate from [1-13C]pyruvate via flux through the pyruvate dehydrogenase (PDH) reaction in healthy subjects compared to those with fatty liver. The long-term purpose of this work is to develop hyperpolarized 13C imaging as a method to directly assess metabolic pathways in the human liver. Many high-impact diseases such as insulin resistant states, fatty liver and inborn errors of metabolism are known to alter biochemical fluxes and for this reason it is important to detect altered activity in specific pathways.

Study Type

Observational

Enrollment (Actual)

22

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390-8568
        • Advanced Imaging Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The plan is to study fatty liver patients and healthy subjects

Description

Inclusion Criteria:

  • Ages 18 to 99 years.
  • All races, ethnicities and gender identification may be included. Subjects must meet all of the inclusion and exclusion criteria to be included in the study.
  • Either fatty liver diagnosis (defined as >5.6% fat content in the liver) or healthy control
  • While all races and ethnicities will be included, subjects must be able to read and speak the English language. Once the protocol is established, Spanish-speaking participants will be included.
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

Fatty Liver Subjects

  • No subjects taking hypoglycemic agents or insulin will be enrolled. There is no exclusion based on fasting glucose.
  • Subjects with major mental health conditions such as schizophrenia and bipolar disorder that would limit compliance with study requirements will not participate. In general, subjects with any form of medical instability such as seizure disorders, significant COPD, significant asthma, left ventricular dysfunction will not participate.
  • Medications for control of hypercholesterolemia, hypertriglyceridemia or hyperglycemia.

Healthy Control Subjects

  • Liver disease or other chronic illness
  • Diagnosis of type I or type II diabetes
  • No subjects taking hypoglycemic agents or insulin will be enrolled. There is no exclusion based on fasting glucose.
  • A potential subject with any major medical, surgical or psychiatric condition will not participate. These conditions include but are not limited to thyroid disease, chronic metabolic illness, known vascular disease, current cancer diagnosis and/or treatment.
  • Subjects with major mental health conditions such as schizophrenia and bipolar disorder that would limit compliance with study requirements will not participate. In general, subjects with any form of medical instability such as seizure disorders, significant COPD, significant asthma, left ventricular dysfunction will not participate.
  • Medications for control of hypercholesterolemia, hypertriglyceridemia or hyperglycemia.

All Subjects

  • No prior hepato-biliary surgery.
  • Donated blood within the prior 4 weeks.
  • Consume more than 10 grams of ethanol per day.
  • Cirrhosis or any form of viral hepatitis.
  • Prior documented hepatic reaction to drugs with a known hepatotoxicity profile such as isoniazid, methotrexate, phenytoin, propylthiouracil, valproate, etc.
  • Pregnant/Lactating
  • Receiving any other investigational agents.
  • Any contraindication noted on the UTSWMC MRI Screening Form including implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD), etc., and significant claustrophobia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Fatty Liver Patients
Hyperpolarized [13C] Pyruvate Injection in Fatty Liver patients
Drug: MRI Tracer
Hyperpolarized [1-13C] pyruvate for injection under IND133229 used to enhance MRI/MRS/MRSI using a 3T MRI scanner.
Healthy Control Subjects
Hyperpolarized [13C] Pyruvate Injection in Healthy Control Subjects
Drug: MRI Tracer
Hyperpolarized [1-13C] pyruvate for injection under IND133229 used to enhance MRI/MRS/MRSI using a 3T MRI scanner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bicarbonate:lactate ratio
Time Frame: One visit of 6 hours; two injections of HP pyruvate with MRI over 3 hours
1. The ratio of hyperpolarized [13C]bicarbonate relative to hyperpolarized [1-13C]lactate. This measurement will be monitored from the subject's liver over a ~4 minute period in the MRI system.
One visit of 6 hours; two injections of HP pyruvate with MRI over 3 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Labeled glycerol fraction
Time Frame: One visit of 6 hours; ingestion of Oral Glycerol with blood draws over 3 hours
2. The fraction of [U-13C]glycerol that has passed through mitochondrial pathways prior to gluconeogenesis and the fraction of glucose, derived from [U-13C]glycerol, that has passed through the pentose phosphate pathway. This information will be acquired from 13C NMR spectroscopy of glucose and triglycerides from a venous blood sample, obtained after the hyperpolarization exam.
One visit of 6 hours; ingestion of Oral Glycerol with blood draws over 3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2018

Primary Completion (Actual)

October 13, 2023

Study Completion (Actual)

October 13, 2023

Study Registration Dates

First Submitted

March 21, 2018

First Submitted That Met QC Criteria

March 21, 2018

First Posted (Actual)

March 29, 2018

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 17, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 082017-019
  • 5P41EB015908-30 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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