Ameliorating Metabolic Profiling After Kidney Transplantation (AMPKT)

NCT05013112 | Completed

• 1 other identifier: WestChinaH-Metformin
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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

Metabolic Disorder; Metformin; Empagliflozin; Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• The primary outcome was the differences in the visceral-to-subcutaneous fat area ratio over 12 months among three groups.

  Based on previous study, visceral-to-subcutaneous fat area ratio, evaluated by CT, was generally reported as a surrogate for metabolic risk and was markedly raised in patients with long-term exposure to steroids. Hence, the primary outcome was the differences in the visceral-to-subcutaneous fat area ratio over 12 months among three groups.

  12 months

Secondary Outcomes (3)

• glycometabolic disorder

  12 months

• lipid metabolism

  12 months

• inflammatory status

  12 months

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

Patients receive no additional therapy.

Other: Placebo

Metformin group

EXPERIMENTAL

Patients receive metformin 500mg twice daily from discharge.

Drug: Metformin

Empagliflozin

EXPERIMENTAL

Patients receive Empagliflozin once daily from discharge.

Drug: SGLT2 inhibitor

Interventions

Metformin DRUG

Metformin 500mg twice daily from discharge

Metformin group

Placebo OTHER

Placebo group

Placebo group

SGLT2 inhibitor DRUG

Empagliflozin 10mg once daily from discharge

Empagliflozin

Eligibility Criteria

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

You may qualify if:

• living-donor kidney transplantation;
• eGFR level \> 45ml/min/1.73m2 at discharge;
• \<Age\<65 years;
• receiving standard triad immunosuppressive regimen.

You may not qualify if:

• previous therapy with metformin or SGLT 2 over the previous 3 months;
• alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 or more of upper limit of normal;
• Combined with HBV/HCV/HIV infection in the donor or recipient;
• Malignancy history in the donor and recipient; 6) organ transplant history in the recipient.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West china hospital

Chengdu, Sichuan, 610000, China

Location

MeSH Terms

Conditions

Metabolic Diseases

Interventions

Sodium-Glucose Transporter 2 Inhibitors; Metformin

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Tao Lin

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 19, 2021
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

CN (1)