Clinical trial NCT06098183: Metabolic Effects of Perimenopause
Official title: Metabolic Effects of Muscle and Exercise Across Perimenopause
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Perimenopausal Disorder
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2023-10-24
Enrollment: 30
Sex: FEMALE
Minimum age (years): 38
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized crossover design
Primary purpose: SUPPORTIVE_CARE

Brief summary: Starting in early-perimenopause, changes in systemic and tissue level metabolism result in an accelerated loss of muscle mass and an increase in body fat. Our preliminary work indicates that metabolic alterations, specifically a decrease in whole-body protein balance, increase in abdominal adiposity, and reduced metabolic flexibility during exercise is most evident in perimenopause. Exercise is a potent stimulator of skeletal muscle insulin sensitivity. High intensity interval training (HIIT) has been shown to be an effective exercise strategy to support cardiometabolic health in overweight and obese young women. Skeletal muscle is critical to maintaining metabolic health and functionality across the lifespan, and is considered the primary diver of whole-body insulin resistance.There is a significant decrease in muscle mass across the menopause transition, which is often exacerbated by a significant gain in fat mass and visceral fat. Protein consumption prior to HIIT has resulted in improvements in energy expenditure and fat oxidation in young women. The overarching objective of this study is to determine the metabolic response of HIIT compared to traditional aerobic exercise in early and late perimenopausal women. Aim 1 will examine the metabolic responses (glucose, insulin sensitivity, energy expenditure) of HIIT vs aerobic exercise, combined with pre-exercise carbohydrate or protein ingestion, in overweight/obese (BMI: 28-40 Kg/m\^2) early and late perimenopausal women. Aim 2 will explore the impact of perimenopause on the fat oxidation and protein turnover before and after exercise. Lastly, aim 3 will explore the modulating effect of intramuscular fat on these metabolic outcomes.


Eligibility criteria: Inclusion Criteria:

* Early and late perimenopausal women (≥38 years; early: experienced menstrual bleeding in the previous 3 months with a decrease in cycle regularity in the past year; late: no menstrual bleeding in the previous 3 months with some bleeding in the previous year).
* Overweight and obese: body mass index (BMI) of 28 - 40 Kg/m\^2 and percent body fat (%BF) ≥ 30%.
* Healthy, non-smokers.

Exclusion Criteria:

* Have current and/or history of cardiovascular disease, diabetes, metabolic, thyroid, pulmonary, renal, hepatic, gastrointestinal, musculoskeletal disorders or medical or surgical events, such as bariatric surgery, heart surgery, or any joint or musculoskeletal injuries or surgeries occurring in the 6-months prior to enrollment, that may significantly influence study outcomes or prevent safe participation.
* Gained or lost \>5 kg in the previous 2 months
* Have a self-identified or clinically diagnosed eating disorder
* Undergone a full or partial hysterectomy for treatment of menopausal symptoms
* Have uncontrolled hypertension or an abnormal electrocardiogram.
* Have an ongoing diagnosed mental disorder with a change in medication in the previous 6 months.
* Taking metabolism-altering drugs or medications outside of estrogen replacement therapy that may influence study outcomes (i.e. corticosteroids, stimulants, insulin, thyroid medications) or phytoestrogens.
* Diagnosed with polycystic ovarian syndrome (PCOS).
* Participating in more than 75 minutes per week of moderate exercise per week.
* Currently pregnant or planning to become pregnant (determined from urine pregnancy test)
* Currently nursing or have had a child within the previous 6 months
* Has participated in another clinical trial within four weeks prior to enrollment that in the opinion of the PI would influence the results.
* Has severely impaired hearing or speech or inability to speak English.
* Unwilling or unable to comply with the study protocol, including abstaining from caffeine, tobacco, alcohol, and physical activity before testing days.

Primary outcomes:
measure: Change in energy expenditure (kcals/day) from baseline and 30 minutes post-exercise.
timeFrame: Baseline and 30 minutes
measure: Change in energy expenditure (kcals/day) from baseline and up to 60 minutes post-exercise.
timeFrame: Baseline and 60 minutes
measure: Change in respiratory exchange ratio (au) from baseline and 30 minutes post-exercise.
timeFrame: Baseline and 30 minutes
measure: Change in respiratory exchange ratio (au) from baseline and up to 60 minutes post-exercise.
timeFrame: Baseline and 60 minutes
Secondary outcomes:
measure: Area under the curve for fat oxidation
timeFrame: Baseline through 60 minutes
measure: Metabolic flexibility
timeFrame: Baseline
measure: Muscle quality
timeFrame: Baseline
measure: Daily Record of Severity of Problems form
timeFrame: Baseline
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Applied Physiology Laboratory - University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Abbie Smith-Ryan, PhD
role: PRINCIPAL_INVESTIGATOR
References: