E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
New onset diabetes after organ-transplantation |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To demonstrate superiority of 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, and aiming for a pre-supper target capillary blood glucose level of 110 mg/dL against post-transplant hyperglycemia, in comparison to conventional treatment, and as evaluated by HbA1c at 3 months post-transplantation (comparison will be made against the simultaneously monitored control group of the ITP-NODAT study [=arm B]) |
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E.2.2 | Secondary objectives of the trial |
• • To determine superiority of SAPT against post-transplant hyperglycemia, in comparison to basal insulin treatment, and as evaluated by HbA1c at 3 months post-transplantation (comparison will be made against the simultaneously monitored basal insulin treatment group of the ITP-NODAT study [=ITP-NODAT study arm A]) • To determine if SAPT with an insulin pump for a period of approximately 3 months post-transplantation, and aiming for a pre-supper target capillary blood glucose level of 110 mg/dL, can prevent intra-individually a clinically meaningful rise in HbA1c (≥0.5%), measured at 3 months post-transplantation • To determine if HbA1c at 6, 12 and 24 months post-transplantation remains at the 3-months level, respectively the baseline level, intra-individually, even after intensive SAPT has been discontinued
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
• 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• 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. • 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]) • Daily glycemia profile, through evaluation of all available glucose measurements • Fasting glucose and 2h glucose at 6, 12 and 24 months after transplantation. • Insulinogenic index during an OGTT at 6, 12 and 24 months after kidney transplantation1. • HOMA-R and QUICKI at 6, 12 and 24 months after kidney transplantation2,3. • OGIS and ISIcomp at 6, 12 and 24 months after kidney transplantation4. • Serum creatinine at 6, 12 and 24 months after kidney transplantation • Patient and graft survival at 6, 12 and 24 months after kidney transplantation • Quality of life measures (mental component summary [MCS] and physical component summary [PCS] derived from the Kidney Disease Quality of Life Short Form (KDQoL-SFTM) at 6, 12 and 24 months after kidney transplantation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |