Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

In Vivo Assessment of Cellular Metabolism in Humans

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: NCT02748369
Recruitment Status : Active, not recruiting
First Posted : April 22, 2016
Last Update Posted : March 8, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
K. Sreekumaran Nair, Mayo Clinic

Brief Summary:
This is a pilot study to establish an arterial venous methodology to measure the activity of the TCA cycle or flux directly in tissues of human beings. It will also perform correlative studies to study the proteome, metabolome, oxygen consumption, carbon dioxide production and exosomes derived from the arterial venous supply of tissues with correlation to the TCA cycle activity.

Condition or disease Intervention/treatment Phase
Normal Cellular Metabolism Drug: Somatostatin Drug: Glucagon Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: In Vivo Assessment of the Tricarboxylic Acid Cycle Flux in the Muscle and Splanchnic Bed of Humans: A Pilot Study
Study Start Date : July 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Control Group
No somatostatin and glucagon infusions
Active Comparator: Intervention Group
Somatostatin and glucagon infusions
Drug: Somatostatin
Somatostatin infusion to create a low insulin state.
Other Name: growth hormone-inhibiting hormone

Drug: Glucagon
Glucagon infusion in the setting of ongoing somatostatin.
Other Name: Glucagen




Primary Outcome Measures :
  1. In Vivo TCA cycle flux in skeletal muscle and splanchnic tissue [ Time Frame: 12 hours ]
    Normal healthy study participants will receive an initial priming dose followed by a continuous infusion of 2-13C-Acetate, 2-15N-Glutamine and D5-Phenylalanine in order to achieve steady state enrichment of 13C and 15N in their system. Serial arteriovenous blood samples will be obtained from the femoral artery, femoral vein and hepatic vein and serial skeletal muscle tissue biopsies will be obtained from the vastus lateralis. These samples will be analyzed by GC-MS and NMR spectroscopy to quantify the isotopomer intermediates of the TCA cycle and measure the corresponding TCA cycle flux. The flux estimations from the arteriovenous blood samples will be compared to that obtained directly from the skeletal muscle tissue. This methodology will be validated in the setting of low insulin levels alone or in combination with high glucagon concentrations.


Secondary Outcome Measures :
  1. Changes in the protein and metabolite contents within circulating exosomes derived from the arterial-venous blood supply of the skeletal muscle and splanchnic tissue [ Time Frame: 12 hours ]
  2. Changes in the metabolome derived from the arterial-venous blood supply of the skeletal muscle and splanchnic tissue [ Time Frame: 12 hours ]
  3. Changes in the proteome derived from the arterial-venous blood supply of the skeletal muscle and splanchnic tissue in response to hormonal manipulation. [ Time Frame: 12 hours ]
  4. Oxygen consumption in skeletal muscle and splanchnic tissue in response to hormonal manipulation [ Time Frame: 12 hours ]
  5. Mitochondrial respiration in skeletal muscle tissue [ Time Frame: 12 hours ]
  6. Reactive oxygen species emissions in skeletal muscle tissue [ Time Frame: 12 hours ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA:

  • Ages 18-45
  • Able to provide written consent

EXCLUSION CRITERIA:

  • Diabetes mellitus or impaired fasting glucose levels (fasting blood glucose >110mg/dl).
  • Renal Failure
  • Pregnancy
  • Steroid use
  • Muscle Disease
  • Liver Disease
  • Major Depression
  • Anemia
  • H/O alcohol use
  • Medications other than OCPs
  • BMI of 30 or greater

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): NCT02748369


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
K. Sreekumaran Nair
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: K Sreekumaran Nair Mayo Clinic

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: K. Sreekumaran Nair, M.D., P.h.D. ; Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02748369     History of Changes
Other Study ID Numbers: 16-000085
U24DK100469 ( U.S. NIH Grant/Contract )
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by K. Sreekumaran Nair, Mayo Clinic:
TCA cycle flux
in vivo measurements
Stable isotopes
Arteriovenous balance
Metabolome
Proteome
Exosomes
Additional relevant MeSH terms:
Layout table for MeSH terms
Glucagon
Glucagon-Like Peptide 1
Somatostatin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents
Incretins