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