Insulin Therapy for the Prevention of New Onset Diabetes After Transplantation Prospective Study in Non-Diabetic De Novo Kidney Transplant Recipients

NCT03507829 | Completed Phase 3

• 1 other identifier: EUDRACT-Nr. 2012-000225-51
• Study Type: interventional
• Target: 263
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to assess the effects of early basal insulin therapy in previously non-diabetic de novo kidney transplant patients in reducing the incidence of new onset diabetes in particular and abnormal glucose metabolism in general during subsequent follow-up.The ITP NODAT study should be seen in connection with the Vienna SAPT-NODAT study (clinicaltrials.gov record number: NCT01680185), as for the final analysis, the data yielded from the three arms in those two studies will be used for an pooled analysis.

Conditions

Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• incidence of NODAT

  The incidence of NODAT 12 months after kidney transplantation defined according to American Diabetes Association criteria

  month 12 after kidney transplantation

Secondary Outcomes (10)

• The incidence of NODAT at 24 months after kidney transplantation

  month 24

• Glycemia profile during the time of insulin therapy in arm A (intervention) comparing that of arm B (control).

  week 0 to week 6

• The glycemia control using A1c levels, overall and among patients with NODAT, through study period 6, 12 and 24 months after kidney transplantation.

  month 6, month 12, month 24

• Incidence of impaired fasting glycemia and impaired glucose tolerance 6, 12 and 24 months after transplantation.

  month 6, month 12, month 24

• Pancreatic beta-cell function at 6, 12 and 24 months after kidney transplantation, measured as insulin secretion during an OGTT in relation to the glucose stimulation (insulinogenic index - total and early phase)

  month 6, month 12, month 24

Study Arms (3)

Basal insulin

ACTIVE COMPARATOR

NPH Insulin Titration Regimen : Pre-dinner Capillary blood glucose NPH dose initiation (IU/day) NPH dose adjustment(IU/day) \> 240 mg/dl 14 Increase by 4 \> 180 mg/dl 12 Increase by 4 \> 140 mg/dl 10 Increase by 4 \> 120 mg/dl 0 Increase by 2 100 to 119 mg/dl 0 Maintain the dose 80 - \<100 mg/dl 0 Decrease by 4 60 - \<80 mg/dl 0 Decrease by 8 \< 60 mg/dl 0 Give ½ of previous dose

Drug: Human insulin isophane, Humulin N (Eli Lilly)

Standard of care

ACTIVE COMPARATOR

Patients assigned in this arm will receive standard of care following their kidney transplantation

Drug: Standard of care

Sensor-augmented Insulin Pump

ACTIVE COMPARATOR

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

Interventions

Human insulin isophane, Humulin N (Eli Lilly) DRUG

Human insulin isophane, Humulin N (Eli Lilly)

Basal insulin

Standard of care DRUG

Sliding scale short acting insulin for hyperglycemia; Sulphonylurea for NODAT

Standard of care

Insulin lispro, Humalog (Eli Lilly) in insulin pump DRUG

Insulin lispro, Humalog (Eli Lilly) in insulin pump

Sensor-augmented Insulin Pump

Eligibility Criteria

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

You may qualify if:

• 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 (once-daily in Europe, twice-daily in the U.S.), mycophenolate mofetil or mycophenolic sodium and steroids.
• Capable of understanding the study and willing to give informed written consent for study participation.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Vienna: lead
• Charite University, Berlin, Germany: collaborator
• Medical University of Graz: collaborator
• Hospital del Mar: collaborator

Related Publications (1)

• Schwaiger E, Krenn S, Kurnikowski A, Bergfeld L, Perez-Saez MJ, Frey A, Topitz D, Bergmann M, Hodlmoser S, Bachmann F, Halleck F, Kron S, Hafner-Giessauf H, Eller K, Rosenkranz AR, Crespo M, Faura A, Tura A, Song PXK, Port FK, Pascual J, Budde K, Ristl R, Werzowa J, Hecking M. Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial. J Am Soc Nephrol. 2021 Aug;32(8):2083-2098. doi: 10.1681/ASN.2021010127.

  PMID: 34330770 DERIVED

MeSH Terms

Conditions

Hyperglycemia

Interventions

Isophane Insulin, Human; Standard of Care; Insulin Lispro

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Insulin, Isophane; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin, Regular, Human; Insulin; Proinsulin; Peptides; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Insulin, Short-Acting

Study Officials

• Manfred Hecking, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ass.Professor Dr.

Study Record Dates

• First Submitted: April 15, 2018
• First Posted: April 25, 2018
• Study Start: November 21, 2012
• Primary Completion: May 22, 2018
• Study Completion: May 22, 2018
• Last Updated: February 19, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share