Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients

The purpose of this study is to investigate whether the anabolic potentials of insulin may be used to reverse the catabolic effects of hemodialysis in non-diabetic patients with end-stage renal failure.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Drug: Glucose-infusion; Drug: Glucose-insulin infusion

Detailed Description

Nutritional markers such as lean body mass and serum albumin are strong predictors of the mortality and morbidity in patients with end-stage renal failure (ESRF) on maintenance hemodialysis (HD). Maintenance HD is considered to contribute to the malnutrition of patients with ESRF, but the exact mechanism has remained unknown. However, we have recently shown that the bioactivity of insulin-like growth factor-I (IGF-I) is reduced by 50% during HD. Furthermore, we showed that the reduction in the bioactivity of IGF-I is directly linked to an up-regulation of IGF-binding protein-1 (IGFBP-1), the only acutely regulated IGFBP, which increased by 6-fold during HD. IGFBP-1 is produced in the liver, primarily under the control of insulin, which promptly inhibits the hepatic production of IGFBP-1. As plasma insulin remains fairly low during a maintenance HD, the increase in IGFBP-1 may be explained by the absence of insulin.

The finding that HD acutely down-regulates the bioactivity of IGF-I by an up-regulation of IGFBP-1 may not only explain the catabolic mechanisms of HD per se, it also opens for a new treatment strategy of ESRF patients undergoing maintenance HD. Thus, on the basis of our previous study we hypothesize that treatment of ERSF patients with high doses of insulin during maintenance HD may counter-act the HD-induced stimulation of IGFBP-1, making it possible to preserve the bioactivity of IGF-I, and thereby abolishing the catabolic impact of HD.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200 N
    • Department of Nephrology, Aarhus University Hospital, Skejby

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 18 years
• stable patients on maintenance hemodialysis for > 3 months
• well-functioning arteriovenous (AV) shunt with recirculation < 5%
• informed consent

Exclusion Criteria:

• diabetes mellitus
• body mass index < 18.5 kg/m2 or > 30 kg/m2
• malnutrition (subjective global assessment (SGA) score C)
• malignancy
• use of immunosuppressive drugs including glucocorticosteroids
• severe infectious disease < 4 weeks
• pregnancy

Exclusion Criteria during the study:

• myocardial infarction or arrythmia with hemodynamic derangements
• permanent thrombosis in the arteriovenous (AV) shunt
• severe infectious disease
• renal transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: No treatment
ACTIVE_COMPARATOR: Glukose-infusion; Glucose-infusion during hemodialysis	Drug: Glucose-infusion; Continuous iv infusion of glucose; Other Names: Glukose
ACTIVE_COMPARATOR: Glucose-insulin infusion; Glucose-insulin infusion during hemodialysis	Drug: Glucose-insulin infusion; Continuous iv infusion of glucose and shortlasting; Other Names: Novorapid; Glukose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of glucose and glucose-insulin infusion on plasma IGF-I and IGFBP-1 during hemodialysis	All patients are randomly assigned to a hemodialysis session with either i) no infusion, ii) a continuous iv infusion of glucose, and iii) a continuous iv infusion of glucose and shortacting insulin. Each dialysis session will be separated by 2 weeks of wash-out	From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis

Secondary Outcome Measures

Outcome Measure	Time Frame
Relationship between inflammatory markers and plasma concentrations of IGF-I and IGFBP-1 during hemodialysis	From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Director: Per Ivarsen, MD, PhD, Department of Nephrology, Aarhus University Hospital, Skejby; Study Director: Jan Frystyk, MD,PhD,DMSc, Department of Endocrinology and Internal Medicine, Aarhus University Hospital; Study Director: Bente Jespersen, MD, DMSc, Department of Nephrology, Aarhus University Hospital, Skejby; Principal Investigator: Mark Reinhard, MD, Department of Nephrology, Aarhus University Hospital, Skejby

Publications and helpful links

General Publications

• Reinhard M, Frystyk J, Jespersen B, Bjerre M, Christiansen JS, Flyvbjerg A, Ivarsen P. Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study. BMC Nephrol. 2013 Apr 4;14:80. doi: 10.1186/1471-2369-14-80.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: September 17, 2010
• First Submitted That Met QC Criteria: September 24, 2010
• First Posted (ESTIMATE): September 27, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): September 30, 2011
• Last Update Submitted That Met QC Criteria: September 29, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Inflammation; Dialysis; Malnutrition; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Binding Protein 1
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin Aspart
• Other Study ID Numbers: IGFHD1-2010; 2010-020114-29 (EUDRACT_NUMBER)