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

August 30, 2012 updated by: Marcus Saemann

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

DESIGN / PHASE:

Prospective, single-center, randomized, parallel group, controlled, phase II study.

STUDY PLANNED DURATION:

First patient First visit 1Q 2009 Last patient First visit 4Q 2009 Last patient Last visit 4Q 2010

CENTERS:

Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria, Department of Surgery, Division of Transplantation, Medical University of Vienna, Austria

PATIENTS / GROUPS:

50 patients in 2 groups 25 patients per group Randomization ratio 1:1, no stratification

Capillary blood glucose will be measured four times daily: before breakfast (7:30 am), before lunch (12 pm), before supper (5:30 pm) and after supper (9 pm) in both groups by the nursing personnel/academic investigators. In group No.1 (study arm 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.

In group No.2 (study arm B), the glucose levels will be recorded, but the treatment will be left up to the ward, which is relying on conventional morning glucose measurements. For safety, any glucose levels >180 mg/dl will be reported, and all measures taken by the ward will be recorded. As there are no available guidelines however concerning the so called "conventional" blood glucose-lowering therapy in renal transplant patients, especially during this very early post-transplant phase, 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 three times daily). 3. Short-acting insulin will be strongly recommended to be used for corrections of capillary blood glucose levels above 250 mg/dl.

EFFICACY ENDPOINTS:

Primary:

- HbA1c levels

Secondary:

  • capillary blood glucose profile in patients treated with long-acting insulin and in the control group, as evaluated by the daily measurements
  • number of patients and overall number of days with hyperglycemia > 140 mg/dl (in each group)
  • number of patients and overall number of days with hyperglycemia > 200 mg/dl (in each group)
  • number of patients and overall number of days with hypoglycemia < 60 mg/dl in each group
  • number of patients with abnormal glucose tolerance on days 90, 180 and 360 after transplantation

TOLERABILITY / SAFETY ENDPOINTS:

- Number of incidences of symptomatic hypoglycemia, confirmed by capillary blood glucose levels < 60 mg/dl

PHARMACOKINETIC / PHARMACODYNAMIC ENDPOINTS:

Doses of (long-acting) insulin

STATISTICAL METHODOLOGY:

Primary Endpoint:

HbA1c (rel %)

Null and alternative hypotheses:

H0 Treatment of hyperglycemia > 140 mg/dl before supper with long-acting insulin in renal transplant recipients for a period of at least 14 days after transplantation is equal to conventional treatment in reducing the HbA1c (measured on day 90 after transplantation).

H1: Treatment of hyperglycemia > 140 mg/dl before supper with long-acting insulin in renal transplant recipients for a period of at least 14 days after transplantation is superior to conventional treatment in reducing the HbA1c (measured on day 90 after transplantation).

Type-I and -II errors - power:

α=0.05 ß=0.2

Statistical methodology:

One-sided t-test of HbA1c on day 90 after transplantation, one-sided t-test of number of days with hyperglycemia > 140 mg/dl before supper, comparison of capillary blood glucose levels by ANOVA

Sample size calculation:

Based on a two-sided testing and an expected standard deviation of HbA1c of 10%, an α=0.05 and a ß=0.2, a sample size of 25 patients per group was determined.

Main analysis set:

Per-protocol (efficacy) and intention to treat (ITT) for safety

Other endpoints:

descriptive statistics

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University of Vienna, Department of Internal Medicine III

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1 Insulatard (long-acting insulin)
Drug: Insulatard (long-acting insulin)
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.
Active Comparator: 2 Conventional treatment
Drug: Conventional
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint is the difference in HbA1c between the two study arms.
Time Frame: post-transplant day 90
post-transplant day 90

Secondary Outcome Measures

Outcome Measure
Time Frame
Capillary blood glucose profiles in each group
Time Frame: post-transplant day 1-21
post-transplant day 1-21
Number of patients and overall number of days with hyperglycemia >140 mg/dl before supper (in each group)
Time Frame: post-transplant day 1 - 21
post-transplant day 1 - 21
Number of patients and overall number of days with hyperglycemia >200 mg/dl (in each group)
Time Frame: post-transplant day 1-21
post-transplant day 1-21
Number of patients and overall number of days with hypoglycemia <60 mg/dl in each group
Time Frame: post-transplant day 1-21
post-transplant day 1-21
Number of patients with abnormal glucose tolerance
Time Frame: post-transplant day 90, 180 and 360
post-transplant day 90, 180 and 360
Difference in HbA1c between the two study arms
Time Frame: post-transplant day 180 and 360
post-transplant day 180 and 360

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Marcus Saemann

Investigators

  • Study Chair: Wilfred Druml, MD, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

January 26, 2009

First Submitted That Met QC Criteria

January 26, 2009

First Posted (Estimate)

January 27, 2009

Study Record Updates

Last Update Posted (Estimate)

September 3, 2012

Last Update Submitted That Met QC Criteria

August 30, 2012

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT: 2008-005951-84

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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