Effects of exercise on mitochondrial response in different age groups

Aging and the Mitochondrial Response to Exercise Training, Measured by Noninvasive 31P Magnetic Resonance Spectroscopy (MoTrMito)

This study tests how different types of exercise can improve muscle health in young, middle-aged, and older adults by looking at how their muscles respond to working out.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 420 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Pennington Biomedical Research Center (other)
• Locations: 1 site (Baton Rouge, Louisiana)
• Trial ID: NCT04799171 on ClinicalTrials.gov

What this trial studies

This study aims to investigate how aerobic and resistance exercise can enhance the mitochondrial capacity of skeletal muscle in healthy adults across various age groups, including young, middle-aged, and older individuals. By utilizing non-invasive 31P magnetic resonance spectroscopy, researchers will measure the biological responses of muscle mitochondria to exercise, providing insights into the mechanisms that contribute to improved metabolic health and functional capacity. The findings may lead to more personalized exercise interventions that target age-related health conditions.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy adults aged 18 and older with a BMI between 19 and 35.

Not a fit: Patients outside the specified age range or with a BMI below 19 or above 35 may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to tailored exercise programs that significantly improve metabolic health and functional capacity in individuals of all ages.

How similar studies have performed: Other studies have shown promising results in understanding the impact of exercise on mitochondrial function, suggesting that this approach is both relevant and potentially impactful.

Eligibility criteria

Inclusion Criteria:

ADULT PARTICIPANT INCLUSION CRITERIA - YOUNG PARTICIPANTS

* Willingness to provide informed consent to participate in the MoTrMito Study
* Must be able to read and speak English well enough to provide informed consent and understand instructions
* Aged 18 - 39 y
* Body Mass Index (BMI) \>19 to \<35 kg/m2

ADULT PARTICIPANT INCLUSION CRITERIA - MIDDLE AGE PARTICIPANTS

* Willingness to provide informed consent to participate in the MoTrMito Study
* Must be able to read and speak English well enough to provide informed consent and understand instructions
* Aged 40 - 59 y
* Body Mass Index (BMI) \>19 to \<35 kg/m2

ADULT PARTICIPANT INCLUSION CRITERIA - OLD AGE PARTICIPANTS

* Willingness to provide informed consent to participate in the MoTrMito Study
* Must be able to read and speak English well enough to provide informed consent and understand instructions
* Aged \>=60 y
* Body Mass Index (BMI) \>19 to \<35 kg/m2

Exclusion Criteria:

ADULT PARTICIPANT EXCLUSION CRITERIA

* 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.

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

Where this trial is running

Baton Rouge, Louisiana

• Pennington Biomedical Research Center — Baton Rouge, Louisiana, United States (RECRUITING)

Study contacts

• Principal investigator: Owen T Carmichael, PhD — Director, Biomedical Imaging Center, PBRC
• Study coordinator: Melissa Harris

Conditions: Physical Activity, Isometric contraction exercise