Clinical trial NCT05135234: Developing a Physiological Understanding of High Duration Activity
Official title: Adaptive Effects of Very Light Physical Activity on Metabolism
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Sedentary Lifestyle
Hyperinsulinemia
Glucose Tolerance Impaired
Low-density-lipoprotein-type
Aging Problems
Lipid Metabolism Disorders
Inactivity, Physical
Metabolic Disorder, Glucose
Keywords: sedentary
physical activity
muscle contractile activity
Lead sponsor: University of Houston
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2021-11-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: When muscles are not contracting, the local energy demand by muscle and use of specific fuels used to produce energy by oxidative metabolism are minimal. The time people spend sitting inactive (sedentary time) typically comprises more than half of the day. This sedentary behavior is associated with elevated risk of diabetes, cardiovascular diseases, some cancers, and multiple conditions leading to poor aging.

From a progressive series of experiments, the driving goal is to develop a physiological method for sustaining contractile activity via oxidative metabolism over more time than is possible by traditional exercise (hours, not minutes per day).

Developing a physiological method suitable of prolonged muscular activity for ordinary people (who are often unfit) requires gaining fundamental insights about muscle biology and biomechanics. This also entails a careful appreciation of the ability to isolate specific muscles in the leg during controlled movements, such as the soleus muscle during isolated plantarflexion. This includes quantifying specific biological processes that are directly responsive to elevated skeletal muscle recruitment. The investigators will focus on movement that is safe and practical for ordinary people to do given their high amount of daily sitting time.

This includes developing methods to optimally raise muscle contractile activity, in a way that is not limited by fatigue, and is feasible throughout as many minutes of the day as possible safely. This also requires development of methodologies to quantify specific muscular activity, rather than generalized body movement.

There is a need to learn how much people can increase muscle metabolism by physical activity that is perceived to them as being light effort. It is important to learn if this impacts systemic metabolic processes under experimental conditions over a short term time span in order to avoid confounding influences of changes in body weight or other factors.

Detailed description: Physical activity/inactivity will be carefully measured with objective devices. Wearable devices most commonly include accelerometers capable of capturing various types of movement and body posture. The intensity of muscle activation (the soleus and other leg muscles) will be measured in some participants in the developmental studies with EMG, with the limb motion quantified with goniometry. Skeletal muscle and whole body metabolism will be evaluated, especially after isolated local contractile activity focusing on the slow oxidative soleus muscle. Blood chemistry will also be investigated in this comprehensive series of studies to understand how replacing sedentary time with low effort muscular activity can be enhanced. Glycemia will be evaluated in the postprandial period in the morning after an overnight fast when there can be standardized control of carbohydrate ingestion. This includes a standardized oral glucose tolerance test with careful experimental assessment of posture and muscular recruitment during the testing periods. One phase of this study is particularly interested in assessing the acute responses that occur immediately as a result of contractile activity, while also evaluating in another phase how this may be impacted by a change in the sedentary lifestyle. This includes assessing new approaches for improving metabolism throughout the day by reducing the amount of time sitting inactive (i.e. sedentary time). Importantly, because the potential immediate benefits of muscle contractile activity are directly dependent on the duration of activity, the investigators aim to develop in a series of experiments how much muscular activity time can be performed comfortably and safely by anybody instead of sitting inactive with low muscle metabolism regardless of age, fitness, body type, and other conditions commonly limiting effectiveness of traditional exercise prescriptions.

Eligibility criteria: Inclusion Criteria:

* Age must be 18 years or older
* Able to fast overnight
* Can maintain diet, medications, and sleep habits between each of the testing visits.
* Lifestyle is consistent with participation in a study evaluating reductions of inactivity (defined by sitting at a low metabolic rate because of minimal muscular activity)
* Willing and able to wear small wearable activity monitors under their clothes as instructed.
* No plans to start a new diet or exercise program if enrolled in the present study.

Exclusion Criteria:

* Practical barriers to completing the study, such as plans to move, or work, or family commitments.
* Plans to change lifestyle during the present study.
* Have physical, vocational, or reasons that prohibit ordinary sitting behaviors present in the modern world.
* Currently dieting to change body weight, or have eating disorder.
* Are pregnant or plan to become pregnant.
* Taking medications that affect bleeding (ie anticoagulants).
* Allergy to lidocaine excludes biopsy component of study.

Primary outcomes:
measure: Oxygen cost of isolated muscle contractions
timeFrame: Acute contractile activity (at least 3 minutes)
measure: Fatigue time during muscle group specific contractile activity
timeFrame: Acute measurements less than 1 day. The exact duration is an individual response that is an outcome of unknown minutes consistent with the fatiguability of different movements.
measure: Change in postprandial glucose regulation
timeFrame: The change through the completion of the postprandial period, an average of 180 minutes
measure: Change in very low density lipoprotein (VLDL) - Triglyceride
timeFrame: The change through the completion of an acute fasting period, approximately 8-12 hours
measure: The change in muscular inactivity time as a result of isolated contractile activity of the soleus
timeFrame: Throughout the waking day (~16 hours).
measure: Angiopoietin-like protein 4
timeFrame: The acute time course during the onset of muscular inactivity and contractile activity within 30 minutes to 8 hours
Secondary outcomes:
measure: Recruited mass of the soleus and other muscles in the triceps surae during isolated plantarflexion
timeFrame: During acute contractile activity of at least 3 minutes
measure: Electrical activity of muscle, Electromyography (EMG)
timeFrame: At least 3 minute recording periods
measure: Local rate of oxygen consumption of working muscle
timeFrame: Steady-state measurements taken for ~6 continuous minutes of contractile activity
measure: The ratio of carbohydrate vs. fat oxidation
timeFrame: Acute responses within less than 24 hours.
measure: Plasma insulin change
timeFrame: The change through the completion of the postprandial period, an average of 180 minutes
measure: Sedentary/muscular inactivity time vs. intermittent non-seated standing behaviors
timeFrame: Throughout the waking day (~16 hours).
measure: apolipoprotein B100 concentration change
timeFrame: After at least 4 weeks of increased contractile activity
measure: Change in the concentration of GlycA (this is not an acronym; it is a biomarker of inflammation)
timeFrame: After at least 4 weeks of increased contractile activity
measure: Small dense LDL concentration change
timeFrame: After at least 4 weeks of increased contractile activity
measure: Complement component 3 (C3) concentration change
timeFrame: After at least 4 weeks of increased contractile activity
measure: Ferritin concentration change
timeFrame: After at least 4 weeks of increased contractile activity
measure: Plasma triglyceride concentration change
timeFrame: After at least 4 weeks of increased contractile activity
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Houston
state: Texas
Study officials:
affiliation: University of Houston
name: Marc T Hamilton, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: