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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03480594
Recruitment Status : Active, not recruiting
First Posted : March 29, 2018
Last Update Posted : October 1, 2021
Sponsor:
Information provided by (Responsible Party):
Craig Riggs Malloy, University of Texas Southwestern Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fatty Liver Drug: Hyperpolarized [13C] Pyruvate Injection Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Non-randomized prospective, non-blinded, single center, translational research
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway (HP FFF)
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fatty Liver Patients
Hyperpolarized [13C] Pyruvate Injection in Fatty Liver patients
Drug: Hyperpolarized [13C] Pyruvate Injection
HP Pyruvate Injection two times during MRI with 45 minute rest period between in Fatty Liver Patients and Healthy Control Subjects
Other Name: HP Pyruvate Injection

Experimental: Healthy Control Subjects
Hyperpolarized [13C] Pyruvate Injection in Healthy Control Subjects
Drug: Hyperpolarized [13C] Pyruvate Injection
HP Pyruvate Injection two times during MRI with 45 minute rest period between in Fatty Liver Patients and Healthy Control Subjects
Other Name: HP Pyruvate Injection




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480594


Locations
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United States, Texas
Advanced Imaging Research Center
Dallas, Texas, United States, 75390-8568
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Publications:

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Responsible Party: Craig Riggs Malloy, Principal Investigator, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03480594    
Other Study ID Numbers: 082017-019
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: October 1, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatty Liver
Liver Diseases
Digestive System Diseases