Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Intracellular Signaling in Muscle and Fat Cells During Ketosis

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: NCT02157155
Recruitment Status : Completed
First Posted : June 5, 2014
Last Update Posted : December 2, 2015
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

Hypothesis

  1. To define whether stimulation of ATGL and suppression of G0/G1 switch gene occur in the initial phases of diabetic ketoacidosis and thus can be identified as the primary mechanisms behind this life threatening condition.
  2. Make a human model for studying ketoacidosis.

The investigators plan to reduce in their regular insulin over night. In the morning we administer endotoxin, which together with a relative lack of insulin will initiate ketogenesis - a state of ketoacidosis. On another occasion strict glycemic control is imposed by means of intravenous insulin. The testing is done two separate days with at least 3 weeks in between and patients are admitted to hospital the evening before the day of testing. The investigators use isotopic tracers to determine metabolic fluxes and analyse fat (ATGL, G0/G1 switch gene) and muscle biopsies.


Condition or disease Intervention/treatment Phase
Ketoacidosis Diabetes Mellitus Type 1 Biological: LPS Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study
Study Start Date : June 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
Insulin reduction and mimic infection with LPS
Biological: LPS
LPS is endotoxin from gram negative bacteria. It is used scientifically to mimic infection lasting 4-8 hours.

No Intervention: Control
Normal insulin and no LPS



Primary Outcome Measures :
  1. Insulin signaling expressed as a CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue. [ Time Frame: Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 (-75min) am t2=11.15 (195min) am t3= 12.30 pm (270min) ]
    Change in phosphorylation of target proteins and messenger RNA (mRNA) expression of target genes assessed with western blotting technique.


Secondary Outcome Measures :
  1. Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies [ Time Frame: Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 am (-75min) t2=11.15 (195min) am t3= 12.30 pm (270min) ]
    Muscle and fat at t1 and t2. Muscle biopsy at t3. Intracellular markers are assessed by western blotting.

  2. Metabolism [ Time Frame: Change in glucose, fat and protein metabolism between study days and during each study day ]
    Change in glucose, fat and protein metabolism assessed by tracer kinetics on every study day (specific times below) and by indirect calorimetry. [3H 3]Glucose tracer from t=0 - 360min. Palmitic acid tracer from t=165min - 360min. Urea tracer from 0min - 240min. amino acid tracer from 60 min - 360 min.

  3. Cytokines and stress hormones [ Time Frame: In basal period t=0-240 minutes and in clamp period t=240-390 minutes ]
    Measurement of immune response to endotoxin and hypoinsulinaemia. Estimating the whole body stress during ketoacidosis and pre ketoacidosis.



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:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetes type 1
  • 19 < BMI < 26
  • minimal or negative C-peptide
  • written consent

Exclusion Criteria:

  • Severe comorbidity
  • regular medication apart from insulin

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): NCT02157155


Locations
Layout table for location information
Denmark
Aarhus University Hospital
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Layout table for investigator information
Principal Investigator: Mads Svart, MD Aarhus University / Aarhus University Hospital
Study Chair: Niels Møller, MD Aarhus University / Aarhus University Hospital
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT02157155    
Other Study ID Numbers: 1-10-72-98-14
First Posted: June 5, 2014    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: June 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus, Type 1
Ketosis
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Acidosis
Acid-Base Imbalance