Metabolic Effects of Perimenopause

NCT06098183 | Completed

• 1 other identifier: 23-2338
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Perimenopausal Disorder

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (4)

• Area under the curve for fat oxidation

  Baseline through 60 minutes

• Metabolic flexibility

  Baseline

• Muscle quality

  Baseline

• Daily Record of Severity of Problems form

  Baseline

Study Arms (2)

Whey protein isolate, then Non-caloric placebo

EXPERIMENTAL

Participants will randomly consume a whey protein isolate (Dymatize ISO-100) mixed with 6 oz of water prior to exercise. After a minimum of 48 hrs they will consume a non-caloric placebo (6 oz of water) prior to exercise.

Other: Whey Protein Isolate; Other: Non-caloric Placebo water

Non-caloric placebo, then Whey protein isolate

PLACEBO COMPARATOR

Participants will randomly consume a non-caloric placebo (6 oz of water) prior to exercise. After a minimum of 48 hrs they will consume a whey protein isolate (Dymatize ISO-100) mixed with 6 oz of water prior to exercise.

Other: Whey Protein Isolate; Other: Non-caloric Placebo water

Interventions

Whey Protein Isolate OTHER

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

Also known as: Dymatize Iso 100

Non-caloric placebo, then Whey protein isolate; Whey protein isolate, then Non-caloric placebo

Non-caloric Placebo water OTHER

Non-caloric placebo

Also known as: Water, placebo

Non-caloric placebo, then Whey protein isolate; Whey protein isolate, then Non-caloric placebo

Eligibility Criteria

• Age: 38 Years - 60 Years
• Gender Eligibility Details: Females identifying as women only
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• American Diabetes Association: collaborator

Study Sites (1)

Applied Physiology Laboratory - University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

Water

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Abbie Smith-Ryan, PhD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized crossover design

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 24, 2023
• Study Start: March 22, 2024
• Primary Completion: August 8, 2025
• Study Completion: August 8, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Beginning 9 and continuing for 36 months following publication
• Access Criteria: Investigator must have approved IRB, IEC, or REB, and an executed data use/sharing agreement with the University of North Carolina.

Locations

US (1)