GLP-1 receptor agonists as preventive treatment of diabetes after renal transplantation: randomized clinical trial. Study 1: Immediate Kidney Transplant Recipients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bellvitge University Hospital, Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

19 Dec 2023 → ongoing

Decision date (initial)

2023-12-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate whether treatment with GLP-1 RA in a high-risk population in the immediate post-kidney transplant period prevents new-onset diabetes after transplantation at 3 months.

Secondary objectives 9

1. Number and type of additional drugs intended for the control of diabetes
2. Insulin sensitivity
3. Influence on weight change, waist circumference and rate of waist-hip circumference
4. Influence on renal function and renal biopsy lesions
5. Influence on lipid profile
6. Incidence of death and death-censored graft loss
7. Differences in levels of immunosuppression
8. Safety of treatment by recording adverse reactions, rate of discontinuations as well as episodes of acute rejection, infection and cardiovascular events.
9. Patients with new-onset diabetes after transplant at 12 months.

Conditions and MedDRA coding

Preventive treatment of post-kidney transplant diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. De novo kidney transplant recipients older than 18 years,
2. No history of diabetes (by clinical history, verbal information from patients directly or with pre-transplant HbA1c ≤ 6.5%),
3. Who receive tacrolimus and prednisone as maintenance immunosuppressive treatment in the post-transplant period
4. And with high risk of PTDM defined by two of these factors: -age > 50 years; -BMI ≥ 30 kg/m2; -first degree family history of diabetes; -hypertriglyceridemia (triglyceride level >2.82 mmol/L); -prediabetes (defined by any of: fasting glucose 100–126 mg/dL (5.6–6.9 mmol/L), or HbA1c 5.7–6.4%, or if available oral glucose tolerance test prior to inclusion with values of initial glucose <126 mg/dL (7 mmol/L) and 2h after the load between 140–200 mg/dL (7.8–11 mmol/L).
5. Women of childbearing potential using effective contraception during study participation.

Exclusion criteria 8

1. Under 18 years of age,
2. previously diagnosed diabetes,
3. Hepatic failure
4. history of pancreatitis (acute or chronic),
5. multiple endocrine neoplasia syndrome type 2 (MEN 2),
6. personal or family history history of medullary thyroid carcinoma (MTC)
7. pregnant or lactating women
8. moderate to severe pre-existing gastroparesis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with prediabetes and diabetes at 3 months after transplant, defined as one of the following criteria of the American Diabetes Association: - patients have a fasting glucose ≥126 mg/dL (7.0 mmol/L), - patients with an abnormal oral glucose tolerance test (OGTT) (value 2-h plasma glucose ≥200 mg/dL (11.1 mmol/L). The test will be carried out according to as described by the WHO, using a glucose load containing the equivalent of 75 g of anhydrous glucose dissolved in water,

Secondary endpoints 10

1. Number and type of additional drugs aimed at diabetes control and metabolic control (HbA1c) and hypoglycemic episodes (defined as ≤ 70 mg/dl) at 3 and 12 months after RT.
2. Insulin sensitivity as measured by homeostatic model assessment calculated for insulin resistance score (HOMA-IR): HOMA-IR = [glucose (nmol/L) * insulin (μU/mL)/22.5], using fasting values and HOMA-measured β-cell function of the β-cell function index (HOMA-B) calculated as the product of 20 and basal insulin levels divided by the value of the basal glucose concentrations minus 3.5 at 3, 6, and 12 months.
3. Weight change measured in kilograms (Kg) and BMI variations from pre-transplant to 3 and 12 months of follow-up; waist circumference and waist-hip circumference ratio measured per cm from pre-transplant to 3 and 12-month follow-up
4. Renal function assessed by routine blood tests: serum creatinine (sCr), estimated glomerular filtration rate (eGFR) (measured by CKD-EPI formulas) and proteinuria measured by spot urine albumin/creatinine ratio (at 3 and 12 months)
5. Lipid profile by routine blood tests: LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, and triglycerides from pre-transplant to 3 and 12-month follow-up
6. Incidence of death and death-censored graft loss
7. Renal biopsy lesions at 12 months: volume fractions of mesangium and mesangial matrix, mesangial expansion (%)
8. Analysis of the differences in the levels of immunosuppression (tacrolimus) in the GLP-1RA group. We will perform the level analysis using the pre-dose concentration of TAC at first steady state (5-7 days after onset), 15 days, 1 and 3 months. We will compare the concentration in blood of the dose standardized CT. Different genotype states of CYP3A4*22 and CYP3A5*3, and P-glycoprotein (3435CT, ABCB1) will be considered in the analysis.
9. Rate of treatment interruptions as well as acute rejection episodes (Biopsy-proven Acute Rejection and Treated Acute Rejection), infection and cardiovascular events
10. Proportion of patients with prediabetes and diabetes at 12 months after transplant.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bellvitge University Hospital

Sponsor organisation

Bellvitge University Hospital

Address

Carrer De La Feixa Llarga Sn

City

L'hospitalet De Llobregat

Postcode

08907

Country

Spain

Scientific contact point

Organisation

Bellvitge University Hospital

Contact name

Nuria Montero

Public contact point

Organisation

Bellvitge University Hospital

Contact name

Nuria Montero

Third parties 1

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso Gallego

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso Gallego

Sponsor responsibilities

Article 77 compliance

Bellvitge University Hospital

Contact point sponsor

Bellvitge University Hospital

Article 77 implementation

Bellvitge University Hospital

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications