The Effects of Intensive Insulin on Somatic and Visceral Protein Turnover in Acute Kidney Injury (AKI)

NCT00592410 | Withdrawn Phase 2

• 1 other identifier: 061022
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

We propose to determine the acute metabolic effects of intensive insulin therapy when administered to AKI patients with a particular focus on its effects on protein metabolism. We hypothesize that the degree of insulin resistance correlates with protein catabolism in critically ill patients with AKI, and that intensive insulin therapy will result in substantial reductions in both whole-body and skeletal muscle protein breakdown thereby improving overall protein balance. We also hypothesize that this therapy will have favorable effects on the inflammatory and oxidative stress profile of patients with AKI. The metabolic response to these interventions will be assessed through stable isotope infusion techniques, allowing for the most precise assessment of protein and energy homeostasis.

Conditions

Acute Renal Failure

Outcome Measures

Primary Outcomes (1)

• A change in whole body and muscle protein breakdown during amino acid supplementation with insulin versus baseline

  6 hours

Study Arms (1)

1

EXPERIMENTAL

Drug: human regular insulin

Interventions

human regular insulin DRUG

administration of a primed continuous infusion of human regular insulin at a rate of 2.0 mU/kg/min while maintaining the plasma glucose level at 100 mg/dl via adjusting a variable infusion of 50% dextrose (i.e., a hyperinsulinemic euglycemic blood glucose clamp); duration of 3 hours; performed concomitantly with amino acid supplementation

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age admitted to the intensive care unit
• New onset acute kidney injury (AKI) or AKI superimposed on chronic kidney disease. AKI will be defined as:
• an abrupt (within 48 hours) sustained increase (\>24 hours) in serum creatinine of 2X baseline or
• a reduction in urine output (documented oliguria of \< 0.5 ml/kg/hr for \>12 hours)
• Patients will be recruited for the study within 3-5 days following establishment of AKI

You may not qualify if:

• Institutionalized patient
• Unable to obtain consent from subject or legally recognized representative
• Pregnancy
• Patients receiving insulin within 12 hours of the study or patients with known diabetes mellitus.
• Patients receiving immunosuppressive medication including steroids (prednisone or equivalent dose ≥ 5 mg PO QD)
• AKI from urinary tract obstruction or a volume responsive pre-renal state.
• Liver Failure, defined as transaminase levels 3 times above the limit of normal or a total Bilirubin greater than 4 mg/dl.
• Evidence of active bleeding, defined as admission for bleeding (ex. GI bleed, ruptured aneurysm, trauma-related) coupled with an explained or unexplained decrease in hemoglobin of \>2 points in the past 24 hours, or Hgb\<8/Hct\<24
• Ongoing myocardial ischemia or heart failure
• Life expectancy \< 48 hours
• Patients without existing central venous access
• Hemodynamically unstable patients requiring active pressor titration, defined as an increase in current pressor dose by \>20% or addition of a new pressor within 12 hours of initiating the study.
• History of Phenylketonuria (PKU) or other documented inborn errors of metabolism
• Hypokalemia, defined as a serum potassium of \<3.0 mg/dl.
• Uncontrolled seizure disorder, defined as having seizure as a reason for admission, ongoing delirium tremens, or having had a seizure within 1 month of the study.

Sponsors & Collaborators

• Vanderbilt University: lead

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Insulin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Alp Ikizler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: January 14, 2008
• Study Start: February 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: August 5, 2011

Record last verified: 2011-08