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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01209403
First received: September 17, 2010
Last updated: September 29, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Kidney Failure, Chronic
Drug: Glucose-infusion
Drug: Glucose-insulin infusion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Insulin-like Growth Factor (IGF-I) in Hemodialysis Patients

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Effect of glucose and glucose-insulin infusion on plasma IGF-I and IGFBP-1 during hemodialysis [ Time Frame: From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Relationship between inflammatory markers and plasma concentrations of IGF-I and IGFBP-1 during hemodialysis [ Time Frame: From 2 h prior to start of hemodialysis to 2 h after end of hemodialysis ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: September 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No treatment
Active Comparator: Glukose-infusion
Glucose-infusion during hemodialysis
Drug: Glucose-infusion
Continuous iv infusion of glucose
Other Name: Glukose
Active Comparator: Glucose-insulin infusion
Glucose-insulin infusion during hemodialysis
Drug: Glucose-insulin infusion
Continuous iv infusion of glucose and shortlasting
Other Names:
  • Glukose
  • Novorapid

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01209403

Locations
Denmark
Department of Nephrology, Aarhus University Hospital, Skejby
Aarhus, Denmark, 8200 N
Sponsors and Collaborators
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
  More Information

No publications provided by University of Aarhus

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01209403     History of Changes
Other Study ID Numbers: IGFHD1-2010, 2010-020114-29
Study First Received: September 17, 2010
Last Updated: September 29, 2011
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by University of Aarhus:
Dialysis
Malnutrition
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 1
Inflammation

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Insulin
Insulin, Globin Zinc
Mitogens
Hypoglycemic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 30, 2014