Mechanisms of Insulin Resistance in Critical Illness: Role of Systemic Inflammation and GLP-1

NCT01347801 | Completed

• 1 other identifier: HS:H-3-2009-108
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.

Conditions

Hypoglycaemia

Keywords

GLP-1; Inflammation; Glucose

Outcome Measures

Primary Outcomes (3)

• Substudy 2C (12 Healthy volunteers): GLP-1

  Increased plasma insulin and C-peptide (intact insulinotropic effect of GLP-1) during GLP-1 infusion in healthy volunteers.

  6 weeks after intervention

• Substudy 2A (12 Healthy volunteers): Insulin, C-peptide and incretin hormone response

  Insulin, c-peptide and incretin hormone response to glucose stimulation during standardized systemic inflammation (TNF infusion) compared to placebo (saline infusion)

  6 weeks after intervention

• Substudy 1C(8 patients, 8 healthy controls): Insulin, C-peptide and incretin hormone response

  Insulin, c-peptide and incretin hormone response to glucose stimulation during IVGTT compared to OGTT in critically ill patients admitted to the ICU

  6 weeks after intervention

Secondary Outcomes (3)

• Substudy 2C (12 Healthy volunteers): Clamp

  6 weeks after intervention

• Substudy 2A (12 Healthy volunteers): The incretin effect

  6 weeks after intervention

• Substudy 1C (8 patients, 8 healthy controls): The incretin effect

  6 weeks after intervention

Study Arms (9)

2C - 1

PLACEBO COMPARATOR

TNF and OGTT and saline

Drug: Placebo (Saline); Drug: TNF-alfa; Other: OGTT

2C - 2

ACTIVE COMPARATOR

TNF and OGTT and GLP-1

Drug: GLP-1; Drug: TNF-alfa; Other: OGTT

2C - 3

PLACEBO COMPARATOR

TNF and IVGTT and saline

Drug: Placebo (Saline); Drug: TNF-alfa; Other: IVGTT

2C - 4

ACTIVE COMPARATOR

TNF and IVGTT and GLP-1

Drug: GLP-1; Drug: TNF-alfa; Other: IVGTT

2A-1

PLACEBO COMPARATOR

Saline infusion and OGTT

Drug: Placebo (Saline); Other: OGTT

2A-2

PLACEBO COMPARATOR

Saline and IVGTT

Drug: Placebo (Saline); Other: IVGTT

2A-3

ACTIVE COMPARATOR

TNF and OGTT

Drug: TNF-alfa; Other: OGTT

2A-4

ACTIVE COMPARATOR

TNF and IVGTT

Drug: TNF-alfa; Other: IVGTT

1C

EXPERIMENTAL

OGTT and corresponding IVGTT

Other: OGTT; Other: IVGTT

Interventions

GLP-1 DRUG

GLP-1 1,2pmol/kg/min i.v. infusion for 4 hours

2C - 2; 2C - 4

Placebo (Saline) DRUG

Normal saline (NaCl 0,9%)

2A-1; 2A-2; 2C - 1; 2C - 3

TNF-alfa DRUG

1000ng/m2 BSA/hour i.v. infusion for 4-6 hours

2A-3; 2A-4; 2C - 1; 2C - 2; 2C - 3; 2C - 4

OGTT OTHER

Oral glucose tolerance test with 75 g glucose

1C; 2A-1; 2A-3; 2C - 1; 2C - 2

IVGTT OTHER

Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT

1C; 2A-2; 2A-4; 2C - 3; 2C - 4

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy (assessed by medical history and clinical examination)
• Age 18-40years
• BMI \< 30kg/m2

You may not qualify if:

• Previous resection of the small intestine (not including the appendix)
• presence of any inflammatory illness during the fortnight preceding the study
• Age\>18 years
• HbA1C\<6,5%
• Admission to the ICU within the last 72 hours

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• University of Copenhagen: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (2)

Centre of Inflammation and Metabolism - Rigshospitalet 7641

Copenhagen, 2100, Denmark

Location

University of Copenhagen

Copenhagen, 2400, Denmark

Location

Related Publications (36)

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MeSH Terms

Conditions

Hypoglycemia; Inflammation

Interventions

Glucagon-Like Peptide 1; Sodium Chloride; Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Kirsten Møller, MD, Ph.D., DMSc

  Centre of Inflammation and Metabolism

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PH.D, DMSc

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 4, 2011
• Study Start: March 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 22, 2014

Record last verified: 2014-09

Locations

DK (2)