A Randomized, Controlled Trial of Personalized, Home-based Exercise Training on Muscle Mitochondrial Function and Metabolism

Description

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

Trial Eligibility

Inclusion Criteria: * Moderate-severe CKD determined by estimated glomerular filtration rate (eGFR) \<60ml/min per 1.73m2 * No history chronic treatment with dialysis. * Age 30 years old to 75 years * Sedentary defined as self-reporting no more than 1 day per week of regular (structured) endurance exercise (EE) \[e.g., brisk walking, jogging/running, cycling, elliptical, or swimming activity that results in feelings of increased heart rate or rapid breathing (EE), and/or sweating\] or resistance exercise (RE) (resulting in muscular fatigue) lasting no more than 60 minutes in the past year. * Persons bicycling as a mode of transportation to/from work \> 1 day/week etc. are not considered sedentary * Leisure walkers are included unless they meet the heart rate, breathing and sweating criteria noted above * Persons adherent to both 1 day/week of RE and 1 day/week of EE are excluded Exclusion Criteria: * Current or previous transplantation * Current pregnancy (all females of child-bearing potential will have a pregnancy test) * Wheelchair dependence or other disability that precludes physical exercise * Oxygen dependent Chronic obstructive pulmonary disease (COPD) * Shortness of breath after walking \<100 steps on flat surface * Weight \>300 pounds * HIV infection or hepatitis viral infection * Decompensated 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 clotting disorder (Deep venous thrombosis, pulmonary embolism) or bleeding disorder. * History of sever heart disease/disorders: coronary artery bypass graft (CABG) surgery, atrial fibrillation * Vascular stent: bare metal or any recently placed (within 6 months) * Current substance abuse * 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. * High dose antioxidants (Vitamine C, Vitamin E) * Baseline systolic blood pressure \>170 or diastolic blood pressure \>100 * Uncontrolled diabetes with a HgbA1c \>8.5 * Active uncontrolled thyroid disease * Anemia (Hgb \<9 g/dL) * Current substance abuse (i.e. amphetamine abuse) * Chronic opioid use (i.e. for chronic pain) * Chronic use of immunosuppressants * Active coronary ischemia detected by ECG on cycle ergometry VO2max testing. These individuals will be promptly referred to their primary care provider by the PI.

Study Info

Interventions

Locations Recruiting

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