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

December 1, 2015 updated by: University of Aarhus

The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

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

  • Denmark
      • Aarhus, Denmark, 8000
        • Aarhus University Hospital

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 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Severe comorbidity
  • regular medication apart from insulin

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

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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)
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.
Change in glucose, fat and protein metabolism between study days and during each study day
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.
In basal period t=0-240 minutes and in clamp period t=240-390 minutes

Collaborators and Investigators

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

Sponsor

University of Aarhus

Investigators

  • Study Chair: Niels Møller, MD, Aarhus University / Aarhus University Hospital
  • Principal Investigator: Mads Svart, MD, Aarhus University / Aarhus University Hospital

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

June 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

May 23, 2014

First Submitted That Met QC Criteria

June 3, 2014

First Posted (Estimate)

June 5, 2014

Study Record Updates

Last Update Posted (Estimate)

December 2, 2015

Last Update Submitted That Met QC Criteria

December 1, 2015

Last Verified

June 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1-10-72-98-14

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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