Ameliorating Metabolic Profiling After Kidney Transplantation (AMPKT)

NCT ID: NCT05013112

Last Updated: 2021-08-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2023-05-01

Brief Summary

Advances in patient selection, organ procurement and preservation, surgical technique, immunosuppression, and infection prevention have conferred significant decrease in rejection, infection, and subsequently improve cause-specific graft failure rates after kidney transplantation (KT). However, cardiovascular diseases (CVD) remained the main burden impairing both short-and long-term survival. Compared with the general population, conventional CVD risk factors, including obesity, liver and muscle insulin resistance, dyslipidemia, hypertension, and diabetes mellitus, are all highly prevalent in this population. Risk factors of these metabolic disorders are generally reported, including common risk factors and those specifically for kidney transplants, including long-term exposure to steroids and calcineurin inhibitors.

Previous studies demonstrated that adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and a key player in regulating cellular energy metabolism. Activation of AMPK by pharmacological agents may hold a considerable potential to reverse the metabolic abnormalities in chronic metabolic diseases. Metformin, a widely used antidiabetic drug, have been reported to act as an AMPK activator by inhibiting complex I of the mitochondrial electron transport chain in many tissues, including adipose, skeletal muscle, and heart. A recent small clinical trial observed that metformin administration did improve some of the metabolic profiles for glucocorticoid-treated patients with inflammatory disease but without pre-existing diabetes. In addition, another antidiabetic drug sodium-glucose-cotransporter-2 (SGLT-2) inhibitors can improve metabolic parameters and cardiovascular risk in patients with or without diabetes in preclinical and clinical studies. A small clinical trial reported that compared to metformin, significant improvement in anthropometric parameters and body composition, in overweight and obese women with polycystic ovary syndrome after 12 weeks of treatment with empagliflozin. Hence, metformin and SGLT2 agents may be used as potential adjuvant therapies to improve metabolic disorders after KT.

However, both metformin and SGLT-2 inhibitors were not recommended in patients with impaired kidney function considering their elimination and action mechanism. Although several preliminary clinical trials showed that metformin and SGLT-2 inhibitors can be used safely and improve glucose control after KT, but they are small-sample sized and only include patients with diabetes. We will conduct a prospective clinical trial with the first aim of exploring the safety of metformin and SGLT-2 inhibitors in kidney transplant recipients with or without diabetes, and the second aim of exploring their roles in improving metabolic profiling.

Conditions

Kidney Transplantation; Metabolic Disorder; Metformin; Empagliflozin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Placebo group

Patients receive no additional therapy.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo group

Metformin group

Patients receive metformin 500mg twice daily from discharge.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin 500mg twice daily from discharge

Empagliflozin

Patients receive Empagliflozin once daily from discharge.

Group Type: EXPERIMENTAL

SGLT2 inhibitor

Intervention Type: DRUG

Empagliflozin 20mg once daily from discharge

Interventions

SGLT2 inhibitor

Empagliflozin 20mg once daily from discharge

Intervention Type: DRUG

Metformin

Metformin 500mg twice daily from discharge

Intervention Type: DRUG

Placebo

Placebo group

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. living-donor kidney transplantation;

2. eGFR level > 45ml/min/1.73m2 at discharge;

3. 18<Age<65 years;

4. receiving standard triad immunosuppressive regimen.

Exclusion Criteria

1. previous therapy with metformin or SGLT 2 over the previous 3 months;

2. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 or more of upper limit of normal;

3. Combined with HBV/HCV/HIV infection in the donor or recipient;

4. Malignancy history in the donor and recipient; 6) organ transplant history in the recipient.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tao Lin

Professor Tao Lin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

WestChinaH-Metformin

Identifier Type: -

Identifier Source: org_study_id