Mitochondrial Function in Patients With Severe Liver Disease (SLDglyc)

The researchers will recruit patients with liver disease at Parkland Hospital. Patients will fast overnight, and the next morning will receive an oral mixture of [U-13C3]glycerol (25 mg/kg) plus unlabeled glycerol (25 mg/kg). The total dose of glycerol will be 50 mg/kg in 100 milliliters of water. The taste is slightly sweet. Blood will be drawn at 60 min and 120 min after the ingestion. Blood glucose will be isolated and analyzed by NMR. The presence of [5,6-13C2]- and [4,5-13C2]glucose indicates preserved mitochondrial function. The researchers anticipate that patients with severe liver disease will show a decrease in mitochondrial function and will inform biosynthetic function of liver mitochondria.

After the first 6 successful exams (see power analysis, below), healthy volunteers (age-, gender-, and race-matched) will be studied at the AIRC and subject to the same protocol.

Study Overview

• Status: Terminated
• Conditions: Hepatic Insufficiency; Hypoalbuminemia
• Intervention / Treatment: Other: Orally administered labeled glycerol

Detailed Description

The researchers will recruit patients with severe liver disease at Parkland Hospital where the procedure will be performed. Age-, gender- and race-matched healthy subjects will be recruited from general population, and the procedure will be performed at the procedure room of the AIRC. Patients at Parkland will be screened and selected by Dr. Jeffrey Browning and Dr. Rodney Infante. After ingestion of 25 mg/kg [U-13C3]glycerol plus 25 mg/kg unlabeled glycerol in water (total glycerol dose, 50 mg/kg), blood will be drawn at +60 and +120 min.

Healthy subjects will make two visits to the AIRC for screening and study procedures. The screening visit will take an hour and the study visit will take 3 hours. Volunteers will be made comfortable in the procedure room of the Research Center. All the study procedures at both Parkland and AIRC will be under the direction of the principal investigator, Dr. Jeffrey Browning.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center - Advanced Imaging Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe liver disease defined as known liver disease plus at least one of the following: serum albumin less than 3.0 g/dL or INR more than 2.0.

Exclusion Criteria:

• Portal systemic encephalopathy
• Pregnancy or breastfeeding.
• Anemia (hematocrit < 32%)
• Significant weight loss or use of diet pills within previous 6 months.
• Cannot give informed consent, understand the protocol, or tolerate any aspect of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orally administered Labeled Glycerol; Patients will receive an oral mixture of [U-13C3]glycerol (25 mg/kg) plus unlabeled glycerol (25 mg/kg). The total dose of glycerol will be 50 mg/kg in 100 milliliters of water.	Other: Orally administered labeled glycerol; Oral administration of labeled glycerol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of 13C in plasma glucose by NMR of a blood sample	Once at 60 minutes post ingestion and once at 120 minutes ingestion for a total ot 2 times	At 60 minutes and 120 minutes post ingestion

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 29, 2015

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hematologic Diseases; Blood Protein Disorders; Hypoproteinemia; Liver Diseases; Liver Failure; Hepatic Insufficiency; Hypoalbuminemia; Physiological Effects of Drugs; Protective Agents; Cryoprotective Agents; Glycerol
• Other Study ID Numbers: STU 022015-085; R01DK099289 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO