Investigating the Effects of Aerobic and Resistance Training in Vivo on Skeletal Muscle Metabolism in Vitro in Primary Human Muscle Cells (MoTrMyo)

Exclusion Criteria

• •Diabetes (self-report and screening tests)
• •* Treatment with any hypoglycemic agents (self-report) or A1c \>6.4 (screening test; may reassess once if 6.5-6.7)
• •* Fasting glucose \>125 (screening test; may reassess once)
• •* Use of hypoglycemic drugs (e.g., metformin) for non-diabetic reasons (self-report)
• •Abnormal bleeding or coagulopathy (self-report)
• •◦History of a bleeding disorder or clotting abnormality
• •Thyroid disease (screening test)
• •* Thyroid Stimulating Hormone (TSH) value outside of the normal range for the laboratory
• •* Individuals with hypothyroidism may be referred to their primary care provider (PCP) for evaluation and retested; any medication change must be stable for ≥3 months prior to retesting
• •* Individuals with hyperthyroidism are excluded, including those with normal TSH on pharmacologic treatment
• •Pulmonary (self-report)
• •◦Clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
• •Metabolic bone disease (self-report)
• •* History of non-traumatic fracture from a standing height or less
• •* Current pharmacologic treatment for low bone mass or osteoporosis, other than calcium, vitamin D, or estrogen
• •Estrogens, progestins (self-report)
• •◦Supplemental, replacement or therapeutic use of estrogens or progestins within the last 6 months, other than birth control or to control menopausal symptoms
• •Pregnancy (screening test) and pregnancy-related conditions (self-report)
• •* Pregnant - pregnancy test performed on day of DXA scan in women of child-bearing potential
• •* Post-partum during the last 12 months
• •* Lactating during the last 12 months
• •* Planning to become pregnant during the participation period
• •Elevated blood pressure readings (screening test)
• •* Aged \<60 years: Resting Systolic Blood Pressure (SBP) ≥140 mmHg or Resting Diastolic Blood Pressure (DBP) ≥90 mmHg
• •* Aged ≥60 years: Resting SBP ≥150 mmHg or Resting DBP ≥90 mmHg
• •* Reassessment of BP during screening will be allowed to ensure rested values are obtained
• •Cardiovascular (self-report, screening test, and clinician judgement)
• •* Congestive heart failure, coronary artery disease, significant valvular disease, congenital heart disease, serious arrhythmia, stroke, or symptomatic peripheral artery disease (self-report, screening test)
• •* Specific criteria used to determine whether a volunteer can undergo the screening Cardiopulmonary Exercise Test (CPET) follow the American Heart Association (AHA) Criteria \[54\]
• •* Inability to complete the CPET
• •Abnormal blood lipid profile (screening test)
• •* Fasting triglycerides \>500 mg/dL
• •* Low-density lipoprotein cholesterol (LDL-C) \>190mg/dL
• •Cancer (self-report)
• •* History of cancer treatment (other than non-melanoma skin cancer) and not "cancer-free" for at least 2 years
• •* Anti-hormonal therapy (e.g., for breast or prostate cancer) within the last 6 months
• •Chronic infection (self-report)
• •* Infections requiring chronic antibiotic or anti-viral treatment
• •* Human Immunodeficiency Virus
• •* Individuals successfully treated for hepatitis C and virologically negative for at least 6 months are not excluded
• •Liver enzyme tests (Alanine transaminase, Aspartate transaminase) (screening test)
• •◦\>2 times the laboratory upper limit of normal
• •* Reassessment during screening may be allowed under some conditions (e.g., recent use of acetaminophen)
• •* Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting
• •Chronic renal insufficiency (screening test)
• •* Estimated glomerular filtration rate \<60 mL/min/1.73 m2 from serum creatinine (mg/dL) by the Chronic Kidney Disease Epidemiology Collaboration equation
• •* Reassessment may be allowed under some conditions (e.g., questionable hydration status or other acute renal insult)
• •Hematocrit (screening test)
• •* Hematocrit \>3 points outside of the local normal laboratory ranges for women and men
• •* Reassessment may be allowed under certain conditions
• •* Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting
• •* Individuals with known thalassemia trait may be included (despite having \>3 points outside of the local normal laboratory ranges), upon approval from their PCP or a hematologist
• •Blood donation (self-report)
• •* Whole blood donation in the last 3 months or plans for blood donation during the entire protocol period
• •* Platelet or plasma donation in the last week or plans for platelet or plasma donation during the entire protocol period
• •Autoimmune disorders (self-report)
• •◦Individuals receiving any active treatment (including monoclonal antibodies) within the last 6 months
• •Alcohol consumption (self-report)
• •* More than 7 drinks per week for women
• •* More than 14 drinks per week for men
• •* History of binge drinking (≥5 drinks for males or ≥4 drinks for females in a 2-hour period more than once per month)
• •Tobacco (self-report)
• •◦Self-reported use ≥3 days/week of tobacco or e-cigarette/e-nicotine products
• •Marijuana (self-report)
• •◦Self-reported use ≥3 days/week in any form
• •Shift workers (self-report)
• •* Night shift work in the last 6 months
• •* Planning night shift work during the study period
• •Cognitive status (screening)
• •◦Unable to give consent to participate in and safely complete the protocol, as based on the judgement of the local investigator
• •Psychiatric illness (self-report and screening test)
• •* Hospitalization for any psychiatric condition within one year (self-report)
• •* Center for Epidemiological Studies-Depression Scale (CESD) score ≥16 \[55\] (screening test)
• •Weight change (self-report)
• •* Weight change (intentional or not) over the last 6 months of \>5% of body weight
• •* Plan to lose or gain weight during the study
• •Lidocaine or other local anesthetic (self-report)
• •◦Known allergy to lidocaine or other local anesthetic
• •Other (clinician judgement)
• •* Any other cardiovascular, pulmonary, orthopedic, neurologic, psychiatric or other conditions that, in the opinion of the local clinician, would preclude participation and successful completion of the protocol
• •* Any other illnesses that, in the opinion of the local clinician, would negatively impact or mitigate participation in and completion of the protocol
• •EXCLUSIONS FOR MEDICATION USE
• •Use of any new drug in the last 3 months
• •Dose change for any drug in the last within 3 months
• •Cardiovascular
• •* Beta blockers and centrally acting anti-hypertensive drugs (clonidine, guanfacine and alpha-methyl-dopa)
• •* Anticoagulants (coumadin or Direct Oral Anticoagulants)
• •* Antiarrhythmic drugs: amiodarone, dronaderone, profafenone, disopyrimide, quinidine
• •* Antiplatelet drugs (other than aspirin ≥100 mg/day): dipyridamole, clopidogrel, ticagrelor
• •* Lipid-lowering medications
• •* Participants who volunteer to stop lipid-lowering medications for the duration of the study are allowed; inclusion requires lipid-lowering medication to be stopped for 3 months and participant re-evaluated for LDL-C eligibility
• •Psychiatric drugs
• •* Chronic use of medium or long-acting sedatives and hypnotics (short-acting non-benzodiazepine sedative-hypnotics are allowed)
• •* All benzodiazepines
• •* Tricyclic antidepressants at a dose ≥75 mg total dose per day
• •* Two or more drugs for depression
• •* Mood stabilizers
• •* Antiepileptic drugs
• •* Stimulants, Attention-Deficit/Hyperactivity Disorder (ADHD) drugs
• •Muscle relaxants
• •◦Methacarbamol; cyclobenzaprine; tizanidine; baclofen
• •Pulmonary, inflammation
• •* Chronic oral steroids
• •* Burst/taper oral steroids more than once in the last 12 months
• •* B2-agonists
• •* allowed if on stable dose at least 3 months
• •Genitourinary
• •* Finasteride or dutasteride
• •* Daily phosphodiesterase type 5 inhibitor use
• •Hormonal
• •* Testosterone, dehydroepiandrosterone, anabolic steroids
• •* Anti-estrogens, anti-androgens
• •* Growth hormone, insulin like growth factor-I, growth hormone releasing hormone
• •* Any drugs used to treat diabetes mellitus or to lower blood glucose
• •* Metformin for any indication
• •* Any drugs used specifically to induce weight loss
• •* Any drugs used specifically to induce muscle growth/hypertrophy or augment exercise-induced muscle hypertrophy
• •Pain/inflammation
• •* Narcotics and narcotic receptor agonists
• •* Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen ≥3 days per week
• •Other
• •* Anti-malarials
• •* Low-potency topical steroids if ≥10% of surface area using rule of 9s
• •Any other medications that, in the opinion of local clinicians, would negatively impact or mitigate full participation and completion