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

This study is currently recruiting participants.
Verified March 2012 by Hospital Universitari de Bellvitge
Sponsor:
Information provided by (Responsible Party):
Josep M Cruzado, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT01561404
First received: March 20, 2012
Last updated: March 21, 2012
Last verified: March 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Disorder Related to Renal Transplantation
Exercise, Aerobic
Muscle Strength
 Drug: Everolimus
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of the Inhibition of the Mammalian Target of Rapamycin on Metabolism and Exercise.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:
  • Muscular strength [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    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:
  • Anthropometric measures [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    Cardioventilatory response measured with respiratory rate, ventilation, oxygen consumption, carbon dioxide production, respiratory quotient and tidal volume during stress test.

  • Metabolic parameters- Biochemical response [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    Lactate and blood glucose levels after stress test

  • Glucose tolerance test [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: Change from baseline to 6-8 weeks after m-TOR conversion ] [ Designated as safety issue: No ]
    Continuos blood preassure measure (24 hours) with a holter monitor device.


Estimated Enrollment: 10
Study Start Date: September 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: m-TOR inhibitor(Everolimus)in kidney transplant recipients

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01561404

Contacts
Contact: Josep M. Cruzado, MD +34932607385 jcruzado@bellvitgehospital.cat
Contact: Carol Polo, PhD +932607385 cpolo@idibell.cat

Locations
Spain
Nephrology Department. Hospital Universitari de Bellvitge Recruiting
L'Hospitalet de Llobregat, Barcelone, Spain, 08907
Principal Investigator: Josep M Cruzado, MD            
Sponsors and Collaborators
Josep M Cruzado
Investigators
Principal Investigator: Josep M. Cruzado, MD Nephrology Department Hospital Universitari de Bellvitge
  More Information

No publications provided

Responsible Party: Josep M Cruzado, NEPHROLOGIST, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT01561404     History of Changes
Other Study ID Numbers: MTOR-METAB, 2009-010541-31
Study First Received: March 20, 2012
Last Updated: March 21, 2012
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
 Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 19, 2013