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Exercise Study Testing Enhanced Energetics of Muscle Mitochondria in CKD (ESTEEM-CKD)

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ClinicalTrials.gov Identifier: NCT02923063
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : October 5, 2016
Sponsor:
Information provided by (Responsible Party):
Bob Roshanravan, University of Washington

Brief Summary:
Skeletal muscle dysfunction (sarcopenia) is an under-recognized target organ complication of CKD with substantial adverse clinical consequences of disability, hospitalization, and death. Sarcopenia in this proposal is defined by impaired metabolism and physical function associated with decreased skeletal muscle mass or function. Skeletal muscle tissue relies on mitochondria to efficiently utilize oxygen to generate ATP. Impaired mitochondrial energetics is a central mechanism of sarcopenia in CKD. The investigators propose a series of studies designed to shed light on the pathophysiology of sarcopenia in persons with CKD not treated with dialysis. Investigators will conduct a randomized-controlled intervention trial of combined resistance training and aerobic exercise vs. health education to assess changes in skeletal muscle mitochondrial function, metabolism and physical function. Investigators hypothesize that exercise improves mitochondrial function and physical function in persons with CKD. If successful, these experiments will identify novel pathophysiologic mechanisms for CKD-associated sarcopenia. The proposed study will provide useful insight into benefits associated with exercise among patients with CKD and investigate mechanisms associated with improved metabolism, muscle function and physical function in population.

Condition or disease Intervention/treatment Phase
Moderate-severe Chronic Kidney Disease Not Treated With Dialysis Non-insulin Dependent Diabetic Kidney Disease Behavioral: Combined Aerobic and Resistance Exercise Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled Trial of Combined Aerobic and Resistance Exercise on Muscle Mitochondrial Function and Metabolism
Study Start Date : September 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Combined Aerobic and Resistance Exercise
Exercise will be supervised by American College of Sports Medicine certified exercise trainers 3 days per week for 12 weeks. Subjects in the exercise intervention arms will undergo supervised low-impact aerobic intervention sessions of 30-minute duration at 60-80% of the maximal heart rate and 30 minutes of resistance exercise training target 60% of single repetition maximal lift (1RM) three times per week. Investigators will use the Balke protocol for treadmill aerobic exercise. Investigators will encourage adherence to the treadmill exercise, however, if the participant declines to use of the treadmill for the day, they will be given other aerobic exercise options (elliptical trainer, cycle, etc.) targeting the same duration and goal heart rate.
Behavioral: Combined Aerobic and Resistance Exercise
No Intervention: Usual Care
At the beginning of the intervention phase, the control group will receive a one-time counseling session on appropriate dietary and physical activity recommendations. They will receive a "Go4Life Workout to go" sample exercise routing created by the national institutes on aging (NIA).



Primary Outcome Measures :
  1. Mitochondrial phosphorylation capacity (ATPmax) by in-vivo 31P MRS/OS [ Time Frame: 12 weeks ]
    Hand and leg muscles

  2. Mitochondrial coupling efficiency (ATP/O2 or P/O) by in-vivo 31P MRS/OS [ Time Frame: 12 weeks ]
    Hand and leg muscles


Secondary Outcome Measures :
  1. Change in physical performance [ Time Frame: 12 weeks ]
    6 minute walking distance (meters)

  2. Change in Systemic oxidative stress (markers of arachidonic acid peroxidation) [ Time Frame: 12 weeks ]
    Plasma isofurans (pg/min)

  3. Change in Muscle Mitochondrial nicotinamide-adenine dinucleotide phosphate from in-vivo MRS [ Time Frame: 12 weeks ]
    mM (millimole)

  4. Change in aerobic capacity (VO2max) (ml/kg/min) [ Time Frame: 12 weeks ]
  5. Change in muscle fatigue [ Time Frame: 12 weeks ]
    Force-time integral (Newtons/second)


Other Outcome Measures:
  1. Muscle mitochondrial reactive oxygen species production from permeabilized muscle fibers. [ Time Frame: 12 weeks ]
    hydrogen peroxide (H2O2) production (pmol/min/mg protein)

  2. Monocyte bioenergetics [ Time Frame: 12 weeks ]
    Reserve Capacity (pmo/min/mcg protein)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Moderate-severe CKD determined by estimated glomerular filtration rate (eGFR) <60ml/min per 1.73m2
  • No history chronic treatment with dialysis.
  • Age 18 years old to 75 years

Exclusion Criteria:

  • Current or previous transplantation
  • Current pregnancy
  • Wheelchair dependence
  • Oxygen dependent Chronic obstructive pulmonary disease (COPD)
  • Shortness of breath after walking <100 steps on flat surface
  • Weight >300 pounds
  • Arm < 47 cm long
  • HIV infection
  • Liver cirrhosis
  • Active malignant cancer other than non-melanomatous skin cancer
  • Drugs that alter mitochondrial function:

    • muscle relaxants (methocarbamol, baclofen, tizanidine, carisoprodol, cyclobenzaprine)
    • oral steroids (Equivalent of 10mg or more of prednisone daily)
    • anti-viral medications (tenofovir, zalcitabine, didanosine, stavudine, lamivudine, zidovudine, abacavir, adefovir, interferon, ribavirin, efavirenz, dasabuvir, ombitasvir)
    • oral calcineurin inhibitors (Tacrolimus, Cyclosporine)
    • Antiepileptic drugs (Phenytoin, phenobarbital, carbamazepine, valproic acid, oxcarbazepine, ethosuximide, zonisamide, topiramate, and vigabatrin)
    • Antipsychotics (haloperidol, thioridazine, risperidone, quetiapine, clozapine, olanzapine and aripiprazole)
  • Drugs- anticoagulants or antiplatelets

    • Anticoagulants, any 1 (coumadin, rivaroxaban, apixaban, dabigatran, edoxaban)
    • Antiplatelets, any 2 (aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticagrelor, ticlopidine, vorapaxar)
  • Implants that prohibit MRI measurements or trauma involving metal fragments
  • Pacemaker
  • History of deep venous thrombosis (DVT) or Pulmonary Embolism (PE)
  • Vascular stent: bare metal or any recently placed (within 6 months)
  • Current substance abuse
  • Pain in arm or leg that would limit laying still for 3-4 hours or undergoing ischemia
  • Polycythemia or thrombocytosis
  • Urine protein/creatinine ratio ≥ 3.5 grams
  • Institutionalization
  • Current participation in an interventional trial
  • Inability to provide informed consent without a proxy respondent
  • Non-English speaking
  • Any condition which in the judgement of the clinical investigator places the participant at risk from participation in the study.

Additional Criteria:

  • On chronic dialysis
  • Expectation to start dialysis within 6 months.
  • Insulin dependent diabetes
  • Baseline systolic blood pressure >170 or diastolic blood pressure >100

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02923063


Contacts
Contact: Baback Roshanravan, MD MS MSPH 2067443948 broshanr@uw.edu

Locations
United States, Washington
Kidney Research Institute, University of Washington Recruiting
Seattle, Washington, United States, 98104
Contact: Bob Roshanravan, MD MS MSPH    206-744-3948    broshanr@uw.edu   
Principal Investigator: Jonathan Himmelfarb, MD         
Sub-Investigator: Bryan Kestenbaum, MD MS         
Sub-Investigator: Bob Roshanravan, MD MS MSPH         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Baback Roshanravan, MD MS MSPH Kidney Research Institute, University of Washington
Principal Investigator: Bryan Kestenbaum, MD MS Kidney Research Institute, University of Washington
Study Director: Jonathan Himmelfarb, MD Kidney Research Institute, University of Washington
Study Director: Ian H de Boer, MD MS Kidney Research Institute, University of Washington
Study Director: Kevin E Conley, PhD University of Washington Translational Center for Metabolic Imaging

Responsible Party: Bob Roshanravan, Acting Instructor, University of Washington
ClinicalTrials.gov Identifier: NCT02923063     History of Changes
Other Study ID Numbers: 52119-A
First Posted: October 4, 2016    Key Record Dates
Last Update Posted: October 5, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Bob Roshanravan, University of Washington:
Chronic Kidney Disease
Mitochondrial Metabolism
Physical Performance
Exercise Intolerance
Muscle Fatigue

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Diabetic Nephropathies
Urologic Diseases
Renal Insufficiency
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases