Metabolic Effects of Perimenopause

Perimenopausal Disorder Clinical Trial

— MAAP  

Official title:

Metabolic Effects of Muscle and Exercise Across Perimenopause

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06098183
• Other study ID #: 23-2338
• Status: Recruiting
• Phase: N/A
• Start date: March 22, 2024
• Est. completion date: July 31, 2027

Study information

• Verified date: October 2023
• Source: University of North Carolina, Chapel Hill
• Contact: Abbie Smith-Ryan, PhD
• Phone: 919-962-2574
• Email: abbiesmith[@]unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 38 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Perimenopausal Disorder

Intervention

Other:
• Whey Protein Isolate
Whey protein isolate essential amino acids (25 g), 5.5 grams of branched-chain amino acids (BCAAs), and 2.7 grams of Leucine per serving
• Non-caloric Placebo water
Non-caloric placebo

Locations

Country	Name	City	State
United States	Applied Physiology Laboratory - University of North Carolina	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	American Diabetes Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in energy expenditure (kcals/day) from baseline and 30 minutes post-exercise.	Indirect calorimetry will be used to obtain energy expenditure prior to exercise and 30 minutes after a bout of high intensity interval training.	Baseline and 30 minutes
Primary	Change in energy expenditure (kcals/day) from baseline and up to 60 minutes post-exercise.	Indirect calorimetry will be used to obtain energy expenditure prior to exercise and 60 minutes after a bout of high intensity interval training.	Baseline and 60 minutes
Primary	Change in respiratory exchange ratio (au) from baseline and 30 minutes post-exercise.	Indirect calorimetry will be used to obtain respiratory exchange ratio prior to exercise 30 minutes after a bout of high intensity interval training.	Baseline and 30 minutes
Primary	Change in respiratory exchange ratio (au) from baseline and up to 60 minutes post-exercise.	Indirect calorimetry will be used to obtain respiratory exchange ratio prior to exercise and 60 minutes after a bout of high intensity interval training.	Baseline and 60 minutes
Secondary	Area under the curve for fat oxidation	Microdialysis of subcutaneous adipose tissue ll be used to obtain fat oxidation prior to exercise and through 60 minutes after a bout of high intensity interval training.	Baseline through 60 minutes
Secondary	Metabolic flexibility	Indirect calorimetry during a ramp exercise protocol	Baseline
Secondary	Muscle quality	Muscle quality measured from magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), and ultrasound will be evaluated.	Baseline
Secondary	Daily Record of Severity of Problems form	Menstrual Related Mood Disorders Daily Rating Form (MRMD) will be measured on a 6 point scale (1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = severe and 6 = extreme), Scores range from 1-6, with higher values indicating worse symptoms.	Baseline