Sensor-Augmented Insulin-Pump Therapy in New-onset Diabetes After Transplantation (SAPT-NODAT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Marcus Saemann, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01680185
First received: August 30, 2012
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

The SAPT-NODAT study will test the hypotheses that intensive subcutaneous insulin treatment with short acting insulin, applied continuously through an insulin pump, (i) improves glycemic control, (ii) reduces the prevalence of NODAT and prediabetes, and (iii) offers further β-cell protection, in comparison to the standard of care control group, and the basal insulin treatment group. In the SAPT-NODAT study, we will employ sensor-augmented insulin-pump technology, which performs like a semi-closed loop to prevent hypoglycemic events. Patients in the SAPT-NODAT study will be followed through 24 months post-transplantation.


Condition Intervention Phase
Hyperglycemia
Drug: Insulin lispro, Humalog (Eli Lilly) in insulin pump
Drug: Human insulin isophane, Humulin N (Eli Lilly)
Other: Standard of care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Treat-To-Target Trial of Continuous Subcutaneous, Sensor-Augmented Insulin-Pump Therapy in New-onset Diabetes After Transplantation (SAPT-NODAT)

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Glycosylated hemoglobin (HbA1c) [ Time Frame: 3 months after transplantation ] [ Designated as safety issue: No ]
    HbA1c levels, in relative %, at 3 months. Superiority will be assumed if a statistically significant difference between the SAPT-treatment group versus the control group (from the ITP-NODAT study) can be determined.


Secondary Outcome Measures:
  • Glycosylated hemoglobin (HbA1c) [ Time Frame: 3, 6, 12, 24 months after transplantation ] [ Designated as safety issue: No ]
    HbA1c, in relative %, at 3, 6, 12 and 24 months post-transplantation; The baseline measurement will also be subtracted from the 3-, 6-, 12-, and 24-months measurement (i.e. "3-months, 6-months, 12-months, and 24-months HbA1c minus baseline HbA1c"). For the determination of the intra-individual rise in HbA1c, the previously observed rise of 0.5±0.7 % (mean ± standard deviation) from baseline to 3 months in the TIP-study basal insulin treatment group will be judged to be clinically not meaningful, hence if the intra-individual rise in the SAPT-treatment group remains below that value, the rise in HbA1c will be considered to be not meaningful, clinically.

  • Oral glucose tolerance test (OGTT)-derived 2 hour-glucose [ Time Frame: 6, 12, 24 months after transplantation ] [ Designated as safety issue: No ]
    2h glucose ≥200 mg/dL, as by OGTT at 6, 12 and 24 months after transplantation (in comparison to the simultaneously monitored control group of the ITP-NODAT study [=arm B; control])

  • Fasting glucose [ Time Frame: 6, 12, 24 months after transplantation ] [ Designated as safety issue: No ]
    Fasting glucose and 2h glucose at 6, 12 and 24 months after transplantation.

  • Beta cell function [ Time Frame: 6, 12, 24 months after transplantation ] [ Designated as safety issue: No ]
    Insulinogenic index during an OGTT at 6, 12 and 24 months after kidney transplantation

  • Insulin sensitivity [ Time Frame: 6, 12, 24 months after transplantation ] [ Designated as safety issue: No ]
    Oral glucose insulin sensitivity (OGIS) index at 6, 12 and 24 months after kidney transplantation

  • Daily glucose measurements [ Time Frame: Daily glucose measurements will be obtained during the hopital stay and while patients are injecting insulin, during an expected average of 3 months. ] [ Designated as safety issue: Yes ]
    Daily glycemia profile, through evaluation of all available glucose measurements

  • Serum creatinine [ Time Frame: 6, 12 and 24 months after transplantation ] [ Designated as safety issue: No ]
    Serum creatinine at 6, 12 and 24 months after kidney transplantation


Estimated Enrollment: 75
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sensor-augmented Insulin Pump
Continuous subcutaneous sensor-augmented insulin-pump therapy (SAPT) with an insulin pump from Medtronic (Paradigm® Velo) for a period of approximately 3 months post-transplantation.
Drug: Insulin lispro, Humalog (Eli Lilly) in insulin pump
all covered above
Active Comparator: Basal insulin
NPH insulin titration regimen, as specified in the IPT-NODAT study
Drug: Human insulin isophane, Humulin N (Eli Lilly)
all covered above
Active Comparator: Standard of care
Patients assigned in this arm will receive standard of care following their kidney transplantation
Other: Standard of care
all covered above
Other Name: Sliding scale short acting insulin for hyperglycemi; Sulphonylurea for NODAT

  Hide Detailed Description

Detailed Description:

Introduction: New-onset diabetes after transplantation (NODAT) is strongly associated with postoperative hyperglycemia, and reduced patient as well as graft survival. In our recent proof-of-concept clinical trial (TIP), we have shown that immediate post-transplant basal insulin therapy decreases hyperglycemia and reduces the prevalence of NODAT by improving pancreatic β-cell function. In consequence, a collaborative multicenter study on NODAT prevention using basal insulin has been approved by the National Institutes of Health (NIH), and will start recruiting 380 patients at 6 international transplant centers, including the Medical University of Vienna and the University of Michigan in 2012. In addition to the NIH-sponsored trial, the Vienna SAPT-NODAT study will test the hypotheses that intensive subcutaneous insulin treatment with short acting insulin, applied continuously through an insulin pump in combination with a glucose sensor (SAPT), (i) improves glycemic control, (ii) reduces the prevalence of NODAT and prediabetes, and (iii) offers further β-cell protection, in comparison to the standard of care control group, and the basal insulin treatment group.

Methods: Combining the NIH-sponsored basal insulin study and the SAPT-NODAT study will yield three study arms, with 25 patients in each arm, namely: [1] the control arm, treated by standard-of-care; [2] the basal insulin arm, treated predominantly with intermediate acting NPH insulin (human insulin isophane, Humulin N, Eli Lilly); [3] the SAPT arm, treated with short acting insulin (Insulin lispro, Humalog, Eli Lilly), applied continuously by SAPT technology. Adult patients with absence of diabetes will be randomized prior to renal transplantation and stratified by deceased donor or living donor, if they are capable of understanding the study and are willing to give informed written consent for all three study arms. Patients will receive standard triple immunosuppressive medications (twice-daily tacrolimus, mycophenolate mofetil or mycophenolic sodium and steroids) with predefined tacrolimus targets and steroid doses. The algorithm for insulin administration is designed to account for the prominent evening peak of hyperglycemia observed in our previous TIP-study. The primary endpoint is HbA1c (in rel.%), at 3 months, and superiority will be assumed if a statistically significant difference between the SAPT-treatment group versus the standard-of-care control group can be determined, by two-sided Student's t-test. Secondary endpoints will be compared between all three groups and will include hypoglycemic events, glycemic variability, 2h glucose ≥200 mg/dL (by oral glucose tolerance test [OGTT] to determine prevalence of diabetes, prediabetes and normal glucose tolerance), beta cell function and insulin sensitivity derived from OGTT, serum creatinine, quality of life measures, patient and graft survival. All secondary endpoint comparisons relying on OGTTs will be made at 6, 12 and 24 months after kidney transplantation, respectively. The result of the 6-months OGTT will be blinded to patients and investigators to prevent subsequent treatment bias.

Discussion: Basal insulin treatment in our previous proof-of-concept study could not prevent a high number of transplant patients exhibiting overt prediabetes (impaired glucose tolerance) at 3, 6 and 12 months, probably on the basis that hyperglycemia was improved, but far from being aggressively treated in patients receiving basal insulin. Prediabetes however is an independent predictor of all-cause mortality in patients after renal transplantation, and therefore not only a harbinger of overt diabetes mellitus but rather a high-risk condition per se. The use of HbA1c as primary endpoint at three months is debatable, but necessary to determine whether SAPT technology may lead to a clinically meaningful improvement of overall glucose control. Specifically, in our previous study (TIP), we observed an intra-individual rise in HbA1c (0.5±0.7 rel.%) from baseline to 3 months, despite basal insulin treatment. If the intra-individual rise in the SAPT arm will remain below that value, SAPT technology could be considered to be a clinically meaningful improvement. The SAPT-NODAT study, besides holding promise to further improve glycemic control, thereby reducing diabetes, prediabetes and possibly cardiovascular events after transplantation, may ensure that the present team of investigators continues to take the lead in post-transplant insulin administration, which is emerging as a central focus in NODAT-prevention and may soon reach broader clinical application.

(Study approval: EK-Nr. 10/2012)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with end stage renal disease undergoing kidney transplantation with a deceased or living donor kidney.
  • Absence of diabetes prior to kidney transplantation, defined according to American Diabetes Association guideline (not on oral hypoglycemic agents or insulin with fasting glucose <126 mg/dL).
  • Receiving standard triple immunosuppressive medications that include tacrolimus, mycophenolate mofetil or mycophenolic sodium and steroids.
  • Capable of understanding the study and willing to give informed written consent for study participation.

Exclusion Criteria:

  • Patients with a diagnosis of diabetes mellitus prior to kidney transplantation, or receiving anti-diabetic medications, or having pre-transplant fasting glucose level equal or greater than 126 mg/dL on two occasions at least three days apart.
  • Patients receiving an organ transplant other than kidney.
  • Patients receiving an unlicensed drug or therapy within one month prior to study entry.
  • Patients with history of hypersensitivity to injectable insulin.
  • Patients with documented HIV infection.
  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: NCT01680185

Contacts
Contact: Manfred Hecking, MD manfred.hecking@meduniwien.ac.at

Locations
Austria
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Principal Investigator: Marcus D Säemann, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Marcus D Säemann, MD Medical University of Vienna
  More Information

No publications provided

Responsible Party: Marcus Saemann, Prof. Dr. Marcus Säemann, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01680185     History of Changes
Other Study ID Numbers: SAPT-NODAT_9march2012
Study First Received: August 30, 2012
Last Updated: September 6, 2012
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Hyperglycemia
NODAT
Insulin pump
Semiclosed loop

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin Lispro
Insulin, Globin Zinc
Insulin, Isophane
Isophane insulin, beef
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014