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

Phase 4

Terminated

• Conditions: Disorder Related to Renal Transplantation; Muscle Strength; Exercise, Aerobic
• Interventions: Drug: Everolimus

• Registration Number: NCT01561404
• Lead Sponsor: Josep M Cruzado

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-03-20
• Study First Submitted QC: 2012-03-21
• Study First Posted: 2012-03-23
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-27
• Last Update Posted: 2015-04-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Everolimus	Everolimus	Conversion from calcineurin inhibitor (CNI) to MTOR inhibitor (everolimus)

Primary Outcome Measures

Name	Time	Method
Muscular strength	Change from baseline to 6-8 weeks after m-TOR conversion	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.
Oxygen consumption in the tissues	Change from baseline to 6-8 weeks after m-TOR conversion	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.

Secondary Outcome Measures

Name	Time	Method
Anthropometric measures	Change from baseline to 6-8 weeks after m-TOR conversion	Measure of anthropometric measures including height,weight, muscular folds( biceps, triceps, subscapular, pectoral, axillary, abdominal, suprailiac, thigh and leg) and perimeters (arm, forearm, wrist, abdominal, waist, hip, thigh, groin, thigh and leg).
Strength of the hand	Change from baseline to 6-8 weeks after m-TOR conversion	Measure of the strenght of the hand will include:test of maximum strength of contraction of the palm, maximum resistance force of the palm and maximum power on a cycle ergometer for 5 seconds with a constant resistance of 50 N.
Metabolic parameters- Cardioventilatory response	Change from baseline to 6-8 weeks after m-TOR conversion	Cardioventilatory response measured with respiratory rate, ventilation, oxygen consumption, carbon dioxide production, respiratory quotient and tidal volume during stress test.
Metabolic parameters- Biochemical response	Change from baseline to 6-8 weeks after m-TOR conversion	Lactate and blood glucose levels after stress test
Glucose tolerance test	Change from baseline to 6-8 weeks after m-TOR conversion
Blood pressure	Change from baseline to 6-8 weeks after m-TOR conversion	Continuos blood preassure measure (24 hours) with a holter monitor device.

Trial Locations

Locations (1)

Nephrology Department. Hospital Universitari de Bellvitge; 🇪🇸 L'Hospitalet de Llobregat, Barcelone, Spain