Effect of the Inhibition of the Mammalian Target of Rapamycin on Metabolism and Exercise

Phase 4TerminatedNCT01561404

Josep M Cruzado3 enrolled

Overview

This is an exploratory study based on the hypothesis that kidney transplant patients treated with an immunosuppressive therapy based on an inhibitor of the mammalian target of rapamycin (m-TOR) may increase resistance to physical exercise, which would result in an improvement in the quality of life of these patients.

The hypothesis of the present study is that, with respect to calcineurin inhibitors, the mTOR inhibitor-based immunosuppression may alter the physical exercise capacity in renal transplant patients. This is based on recent data obtained. Regarding metabolism there is evidence that inhibition of mTOR, reduces muscle glucose utilization, as well as, increase fatty acid oxidation. On the other hand, has shown that drugs based on mTOR inhibitors in the context of excess of nutrients improves intracellular glucose uptake in skeletal muscle cells. Through these mechanisms could increase resistance to physical exercise, which would result in an improvement in the quality of life of patients. Nevertheless, there isn't any paper that has explored this hypothesis accurately.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Interventions

EverolimusDRUG

In patients that change of immunosuppressive therapy from calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) to m-TOR (everolimus)has been clinically indicated, check if there is an increase in physical exercise capacity.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Renal transplant patient's aged between 18 and 60 years old. 2. Heart rate in radial pulse and seated between 50 and 100 bpm. 3. Systolic blood pressure between 100 and 140 and diastolic between 50 to 90. 4. Absence of any clinical physical, psychological or psychiatric condition that would prevent from the protocol described follow-up. 5. Estimated glomerular filtration rate greater than 40 ml / min. 6. Proteinuria \< 0.5 g / d. 7. Renal transplantation at least 6 months ago. 8. Immunosuppressant based on calcineurin inhibitors. 9. Hemoglobin \> 11 g / dl. 10. Body mass index (BMI) \< 35 kg/m2. 11. Indication for conversion to everolimus and granting of written informed consent. Exclusion Criteria: 1. Diabetes mellitus 2. Treatment with erythropoiesis stimulating drugs 3. Treatment with β blockers drugs 4. Participation in any clinical trial in the last 30 days prior to the inclusion. 5. Any other physical illness, psychological or psychiatric condition that could difficult the follow-up of the patient.

Locations (1)

Nephrology Department. Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelone, Spain

Outcomes

Primary Outcomes

Muscular strength

The principal variable is the increase of the exercise capacity measured by 2 sub-varibles: muscular strenght and decrease of oxygen consumption in the tissues.