Treat-to-target Trial of Basal Insulin in Post-transplant Hyperglycemia

NCT00830297 | Completed Phase 2

• 1 other identifier: EudraCT: 2008-005951-84
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Treat-to-target trial of basal Insulin in Post-transplant hyperglycemia (TIP): efficacy and safety of a novel protocol in renal transplant recipients receiving a tacrolimus-based immunosuppression DESCRIPTION: A prospective, randomized safety and efficacy study of long-acting insulin (Insulatard®) as therapy against post-transplant hyperglycemia in renal transplant recipients OBJECTIVES: Primary Objective: To demonstrate superiority of long-acting insulin (Insulatard®) against post-transplant hyperglycemia, in comparison to conventional treatment, and as evaluated by HbA1c Secondary Objectives:

• To assess the average post-transplant glucose levels in renal transplant patients under conventional blood-glucose lowering therapy during a period of at least 14 days after transplantation by measuring the capillary blood glucose levels four times daily in both groups of patients (fasting, before lunch, before supper, after supper)
• To detect the number of post-transplant patients who - without any history of pre-transplant diabetes - develop at least one episode of post-transplant hyperglycemia (\> 140 mg/dl before supper)
• To detect the average number of hyperglycemic episodes in post-transplant patients with at least one episode of post-transplant hyperglycemia and without any history of diabetes
• To assess the amount of (long-acting) insulin (in IU) needed in order to obtain a target capillary blood glucose level in the range of 110 mg/dl to 120 mg/dl before supper in post-transplant patients with incidence of hyperglycemia
• To assess the safety of long-acting insulin in controlling post-transplant hyperglycemia (especially with regards to episodes of hypoglycemia (glucose-level \< 60 mg/dl)
• To assess the prevalence of post-transplant diabetes, as diagnosed by an abnormal oral glucose tolerance on days 90, 180 and 360 after transplantation, in the group of patients which has been treated with long-acting insulin, in comparison to patients who received conventional treatment
• To assess the morbidity (hospitalization, infections, subsequent episodes of surgery, requirement of non-immunosuppressive, non- blood glucose lowering medication) in the group of patients with long-acting insulin for hyperglycemia, in comparison to patients randomized into the group receiving conventional treatment
• To assess the renal outcome (creatinine levels, rejections) in the group of patients which is foreseen to be treated with long-acting insulin for hyperglycemia, in comparison to patients randomized into the group receiving conventional treatment

Conditions

Hyperglycemia

Keywords

TIP; NODAT; hyperglycemia; long-acting insulin; post-transplant hyperglycemia

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the difference in HbA1c between the two study arms.

  post-transplant day 90

Secondary Outcomes (6)

• Capillary blood glucose profiles in each group

  post-transplant day 1-21

• Number of patients and overall number of days with hyperglycemia >140 mg/dl before supper (in each group)

  post-transplant day 1 - 21

• Number of patients and overall number of days with hyperglycemia >200 mg/dl (in each group)

  post-transplant day 1-21

• Number of patients and overall number of days with hypoglycemia <60 mg/dl in each group

  post-transplant day 1-21

• Number of patients with abnormal glucose tolerance

  post-transplant day 90, 180 and 360

Study Arms (2)

1 Insulatard (long-acting insulin)

ACTIVE COMPARATOR

Drug: Insulatard (long-acting insulin)

2 Conventional treatment

ACTIVE COMPARATOR

Drug: Conventional

Interventions

Insulatard (long-acting insulin) DRUG

In group No.1 (study arm 1 (=A)), patients will be treated with long-acting insulin (Insulatard) as soon as the glucose-level before supper surpasses 140 mg/dl. The normoglycemic goal in this group will be from 110 to 120 mg/dl.

1 Insulatard (long-acting insulin)

Conventional DRUG

In group No.2 (study arm 2 (=B)), patients will be treated conventionally according to the decisions taken by the physicians on the ward. The following suggestions will be brought to the attention of the ward in order to standardize the treatment of the patients in study arm B: 1. Treatment in this group should be initiated if the fasting glucose level surpasses the renal glucose threshold, i.e. 180 mg/dl. 2. As the proposed life-style modifications for the treatment of NODAT1 are not feasible during this very early post-transplant phase, the basis of the conventional therapy will be proposed to be sulfonyl urea drugs (i.e. Gliclazide - Diamicron®, 30 mg, not more than twice daily). 3. Short-acting insulin will be strongly recommended to be used for corrections of capillary blood glucose levels above 250 mg/dl.

2 Conventional treatment

Eligibility Criteria

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

You may qualify if:

• renal transplantation (deceased or living donor)
• eligibility for the standard immunosuppression of our center, consisting of tacrolimus, mycophenolate mofetil or mycophenolic acid, dexamethasone/prednisone triple therapy
• informed consent of the patient

You may not qualify if:

• patients with type 1 or type 2 diabetes
• allergy against long-acting insulin

Sponsors & Collaborators

• Marcus Saemann: lead

Study Sites (1)

Medical University of Vienna, Department of Internal Medicine III

Vienna, 1090, Austria

Location

Related Publications (2)

• Davidson JA, Wilkinson A; International Expert Panel on New-Onset Diabetes after Transplantation. New-Onset Diabetes After Transplantation 2003 International Consensus Guidelines: an endocrinologist's view. Diabetes Care. 2004 Mar;27(3):805-12. doi: 10.2337/diacare.27.3.805. No abstract available.

  PMID: 14988309 BACKGROUND

• Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.

  PMID: 32803882 DERIVED

MeSH Terms

Conditions

Hyperglycemia

Interventions

Isophane Insulin, Human; Insulin, Long-Acting; Congresses as Topic

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Insulin, Isophane; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin, Regular, Human; Insulin; Proinsulin; Peptides; Amino Acids, Peptides, and Proteins; Organizations; Health Care Economics and Organizations

Study Officials

• Wilfred Druml, MD

  Medical University of Vienna

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ass. Prof. Dr. Marcus Säemann

Study Record Dates

• First Submitted: January 26, 2009
• First Posted: January 27, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: May 1, 2011
• Last Updated: September 3, 2012

Record last verified: 2012-08

Locations

AU (1)