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

Kidney Failure, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01209403
• Other study ID #: IGFHD1-2010
• Secondary ID: 2010-020114-29
• Status: Completed
• Phase: Phase 4
• First received: September 17, 2010
• Last updated: September 29, 2011
• Start date: September 2010
• Est. completion date: July 2011

Study information

• Verified date: September 2011
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Regional Committee on Biomedical Research EthicsDenmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Glucose-infusion
Continuous iv infusion of glucose
• Glucose-insulin infusion
Continuous iv infusion of glucose and shortlasting

Locations

Country	Name	City	State
Denmark	Department of Nephrology, Aarhus University Hospital, Skejby	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No