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

University of Aarhus

Status and phase: Completed; Phase 4

Conditions: Kidney Failure, Chronic

Treatments: Drug: Glucose-infusion; Drug: Glucose-insulin infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT01209403

2010-020114-29 (EudraCT Number)

IGFHD1-2010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

No treatment

No Intervention group

Glukose-infusion

Active Comparator group

Description:

Glucose-infusion during hemodialysis

Treatment:

Drug: Glucose-infusion

Glucose-insulin infusion

Active Comparator group

Description:

Glucose-insulin infusion during hemodialysis

Treatment:

Drug: Glucose-insulin infusion