Effect of the Inhibition of the Mammalian Target of Rapamycin on Metabolism and Exercise (EXETOR)

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

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.

Study Overview

• Status: Terminated
• Conditions: Muscle Strength; Disorder Related to Renal Transplantation; Exercise, Aerobic
• Intervention / Treatment: Drug: Everolimus

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelone
    • L'Hospitalet de Llobregat, Barcelone, Spain, 08907
      • Nephrology Department. Hospital Universitari de Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus; Conversion from calcineurin inhibitor (CNI) to MTOR inhibitor (everolimus)	Drug: Everolimus; 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.; Other Names: m-TOR inhibitor(Everolimus)in kidney transplant recipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Change from baseline to 6-8 weeks after m-TOR conversion
Oxygen consumption in the tissues	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.	Change from baseline to 6-8 weeks after m-TOR conversion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric measures	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).	Change from baseline to 6-8 weeks after m-TOR conversion
Strength of the hand	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.	Change from baseline to 6-8 weeks after m-TOR conversion
Metabolic parameters- Cardioventilatory response	Cardioventilatory response measured with respiratory rate, ventilation, oxygen consumption, carbon dioxide production, respiratory quotient and tidal volume during stress test.	Change from baseline to 6-8 weeks after m-TOR conversion
Metabolic parameters- Biochemical response	Lactate and blood glucose levels after stress test	Change from baseline to 6-8 weeks after m-TOR conversion
Glucose tolerance test		Change from baseline to 6-8 weeks after m-TOR conversion
Blood pressure	Continuos blood preassure measure (24 hours) with a holter monitor device.	Change from baseline to 6-8 weeks after m-TOR conversion

Collaborators and Investigators

• Sponsor: Josep M Cruzado
• Investigators: Principal Investigator: Josep M. Cruzado, MD, Nephrology Department Hospital Universitari de Bellvitge

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): April 28, 2015
• Last Update Submitted That Met QC Criteria: April 27, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: MTOR-METAB; 2009-010541-31 (EudraCT Number)