Clinical trial NCT01209403: Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients
Official title: Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Failure, Chronic
Keywords: Dialysis
Malnutrition
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 1
Inflammation
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2010-09-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of glucose and glucose-insulin infusion on plasma IGF-I and IGFBP-1 during hemodialysis
timeFrame: From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis
Secondary outcomes:
measure: Relationship between inflammatory markers and plasma concentrations of IGF-I and IGFBP-1 during hemodialysis
timeFrame: From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Nephrology, Aarhus University Hospital, Skejby
Study officials:
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby
name: Per Ivarsen, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
name: Jan Frystyk, MD,PhD,DMSc
role: STUDY_DIRECTOR
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby
name: Bente Jespersen, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Nephrology, Aarhus University Hospital, Skejby
name: Mark Reinhard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.