A Two-Way Path to Health: Environmental Influences on Skeletal Muscle Endocrine Function

NCT07706465 | Not Yet Recruiting

• 1 other identifier: NdRS/SP/0034/2025/01
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

Given the well-established anti-inflammatory and health-promoting effects of physical activity as a non-pharmacological intervention, an important question remains whether different types of exercise differ in their ability to reduce the body burden of per- and polyfluoroalkyl substances (PFAS) and whether PFAS exposure modifies exercise-induced adaptive responses. The investigators hypothesize that the coexistence of physical inactivity, overweight/obesity, reduced muscle mass, and consequently lower concentrations of myokines/exerkines contributes to impaired cardiovascular function, reduced exercise capacity, and a greater PFAS body burden. Collectively, these factors may adversely affect work ability, reduce occupational participation, and discourage continued employment among middle-aged women. In the context of unfavorable demographic trends, such consequences may represent a significant economic burden for society. The primary objective of this project is to determine whether baseline PFAS concentrations are associated with the health status of women entering the study and to characterize circulating profiles of myokines/exerkines and arginine metabolites. A secondary objective is to compare the effects of different exercise programs on PFAS concentrations and their potential elimination from the body. In addition, we will investigate whether a history of cancer treatment, despite increasingly favorable clinical outcomes, is associated with long-term alterations in skeletal muscle endocrine function, myokine and exerkine release, and PFAS body burden. The study will include perimenopausal women. Participants will be allocated to one of two supervised exercise programs: high-intensity circuit training (HICT) or interval walking training (IWT). Both interventions will last six months and will be performed two times per week (with possible additional unit performed at home). This period will be followed by six months of unsupervised maintenance training. Two additional groups will be included: a control group maintaining their usual lifestyle and a group of women who have completed cancer treatment. Participants in the oncology group will be instructed to maintain a daily physical activity level of approximately 7,000-10,000 steps. Assessments will be performed at baseline, immediately after the intervention, and six months after its completion. Circulating concentrations of selected myokines, exerkines, arginine metabolites, and 18 PFAS compounds will be measured in blood, while PFAS concentrations will also be determined in urine samples. Cardiorespiratory fitness, body composition assessed by dual-energy X-ray absorptiometry (DXA), dietary habits, quality of life, and health literacy will also be evaluated.

Conditions

Healthly Volunteers; Oncologic Disease

Keywords

PFAS; skeletal muscle endocrine function; myokines and exerkines; physical activity; perimenopausal women; exercise adaptation; women's health

Outcome Measures

Primary Outcomes (17)

• Blood Cell Counts (×10⁹/L)

  Blood Cell Counts (×10⁹/L): White Blood Cell Count (WBC), Platelet Count (PLT), Neutrophil Count (NEUT), Lymphocyte Count (LYMPH), Monocyte Count (MONO), Eosinophil Count (EOS), and Basophil Count (BASO) will be determined using standard analytical method.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Leukocyte Differential Percentages (%)

  The percentages (%) of neutrophils (NEUT), lymphocytes (LYMPH), monocytes (MONO), eosinophils (EOS), and basophils (BASO) will be determined as part of the complete blood count with differential.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Red Blood Cell Count (RBC)

  Red Blood Cell Count (×10¹²/L)

  At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Blood Concentrations

  Blood Concentrations (g/dL): Hemoglobin Concentration (HGB) and Mean Corpuscular Hemoglobin Concentration (MCHC).

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Hematological Volume Indices

  Hematological Volume Indices (fL): Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV).

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Mean Hemoglobin Content

  Mean Hemoglobin Content (pg): Mean Corpuscular Hemoglobin (MCH).

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Hematological Percentage Indices

  Hematological Percentage Indices (%): Hematocrit (HCT), Red Cell Distribution Width (RDW), Platelet Distribution Width (PDW), Plateletcrit (PCT), and Platelet Large Cell Ratio (P-LCR) .

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Irisin, BDNF, IL-6, gp130, sIL-6R, IL-15, IL-15Rα, decorin, myostatin, follistatin, MuRF1, and Lac-Phe

  Selected myokines and exerkines, including irisin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), gp130, soluble IL-6 receptor (sIL-6R), IL-15, IL-15Rα, decorin, insulin, myostatin, follistatin, muscle RING-finger protein-1 (MuRF1; an E3 ubiquitin ligase commonly used as a marker of muscle atrophy), and N-lactoyl-phenylalanine (Lac-Phe), will be quantified using enzyme-linked immunosorbent assays (ELISA) with commercially available high-sensitivity kits from reputable manufacturers. Blood serum or plasma will be used (as per requirements). All proteins will be expressed in ng/ml.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• T-Lymphocyte Subpopulation Percentages (%)

  The percentage (%) of CD4⁺CCR7⁺, CD8⁺CCR7⁺, CD4⁺CD28⁺, and CD8⁺CD28⁺ cell populations will be determined by flow cytometry.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• L-arginine, L-citrulline, L-ornithine, ADMA, SDMA

  Arginine metabolites will be quantified in serum using the isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) technique, which has been successfully applied in our previous studies. All metabolites will be expressed in ng/ml.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Per- and Polyfluoroalkyl Substances (PFAS)

  PFAS concentrations in plasma and urine samples will be quantified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). A panel of 18 PFAS, among the most commonly detected and widely used, has been selected for analysis. All PFAS will be expressed in ng/ml.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Inflammatory ratio

  Inflammatory hematological ratios Indicators of inflammation (Neutrophil to Lymphocyte ratio, Monocyte to Lymphocyte ratio, Platelet to Lymphocyte ratio) will be calculated made based on hematological medical records.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• HOMA-%B, HOMA-%S,

  Indices of insulin resistance and insulin sensitivity, including pancreatic β-cell function (HOMA-%B), insulin sensitivity (HOMA-%S) will be calculated.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Blood glucose

  Blood glucose concentration (mg/dl) will be measured using standard analytical methods.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Glycated hemoglobin

  Glycated hemoglobin (HbA1c) (%) will be measured using standard analytical methods.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Insulin

  Serum insulin ( µIU/ml ) concentration will be measured using a high-sensitivity immunoenzymatically assay according to the manufacturer's instructions.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Insulin resistance

  Insulin resistance (HOMA-IR) will be calculated.

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

Secondary Outcomes (15)

• Oxygen uptake at rest, at anaerobic threshold and maximal intensity

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Oxygen uptake at rest, at anaerobic threshold and maximal intensity

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Heart Rate

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Body Height

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

• Total body mass, Total fat mass, Total lean mass, Android fat mass, Gynoid fat mass, Intra-Cellular Water, Extra-Cellular Water, Total Body Water, Bone Mass component

  "At day 1" "after 6 months on day 1" "On average, in 1 year from day 1"

Other Outcomes (2)

• Socio-demographic characteristics

  On day 1

• Clinical history

  On day 1

Study Arms (4)

Control Group

NO INTERVENTION

The healthy, control group (n = 70) will be included in the study. Assessments will be conducted at three time points. Participants will be instructed not to modify their usual lifestyle throughout the study period.

IWT- Interval Walking Training

EXPERIMENTAL

The healthy IWT group- a six-month supervised exercise intervention conducted under the supervision of a qualified exercise trainer.

Other: Experimental: IWT- Interval Walking Training

HICT-High Intensity Circuit Training

EXPERIMENTAL

The healthy HICT group - a six-month supervised exercise intervention conducted under the supervision of a qualified exercise trainer.

Other: Exercise training II

Onco-female group

EXPERIMENTAL

A group of female cancer survivors will be included in the study. Participants will be encouraged to achieve a moderate level of physical activity equivalent to approximately 8,000 steps per day. Physical activity will be continuously monitored using wearable step-counting devices, and compliance with the prescribed activity will be regularly supervised by a physiotherapist.

Other: Walking

Interventions

Experimental: IWT- Interval Walking Training OTHER

Interval Walking Training will consist of five repetitions of alternating 3-minute intervals of fast and slow walking, resulting in a total exercise duration of 30 minutes per session. The training period will last 6 months, two training session/a week.

IWT- Interval Walking Training

Exercise training II OTHER

HICT training will consist of ten exercises: jumping jacks, push-ups, abdominal crunches, squats, planks, triceps dips using a chair, high knees (running in place), lunges, push-ups with rotation, and side planks. Each exercise will be performed for 30 seconds, followed by a 10-second transition period. A 2-minute rest period will be provided between sets. Training period will last 6 monts /a two training session a week

HICT-High Intensity Circuit Training

Walking OTHER

Walking training is addressed to breast cancer patients who have already finished onco-treatment. Participants will be instructed to maintain a daily step count of 7,000-10,000 steps throughout the study period.

Onco-female group

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women,
• aged 35-75 years
• qualified by a physician for participation in the study and with no contraindications to the training intervention (e.g., heart failure, asthma, chronic obstructive pulmonary disease \[COPD\], or arthritis)
• Women ,
• aged 35-75 years,
• Diagnosed with invasive breast cancer, Stage I-III disease according to the TNM classification,
• Estrogen receptor-positive (ER+) breast cancer, defined as expression in at least 10% of tumor cell nuclei,
• Adjuvant hormone therapy with an aromatase inhibitor for at least 6 months,
• BMI between 18.5 and 32 kg/m².
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• No chronic diseases limiting the possibility of oncological treatment.
• No contraindications to daily physical activity.
• Willingness to maintain a daily step count of 8,000 steps.

You may not qualify if:

• history of cardiovascular disease,
• previous hospitalization for cardiovascular conditions,
• ongoing cardiovascular treatment, or recent cardiovascular symptoms,
• advanced osteoporosis
• Stage IV invasive breast cancer according to the TNM classification.
• ECOG performance status ≥2.
• Unstable ischemic heart disease.
• Cardiac arrhythmias.
• Advanced degenerative joint disease.
• Rheumatic disorders (including rheumatoid arthritis, osteoarthritis, or fibromyalgia).
• Progression of chronic diseases.
• Pregnancy.
• BMI \<18.5 or \>32 kg/m².
• Uncontrolled hypothyroidism or hyperthyroidism.

Sponsors & Collaborators

• Poznan University of Physical Education: lead

MeSH Terms

Conditions

Motor Activity

Interventions

Exercise; Walking

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Locomotion

Study Officials

• Urszula Czerniak, PhD

  Poznan University of Physical Education

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marzena Szerment, MA

CONTACT

0048618355061; marzena.szerment@awf.poznan.pl

Ewa Ziemann, Professor

CONTACT

0048606330944; ewa.ziemann@awf.poznan.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will recruit 170 women into the training groups: IWT training, n=85, HICT: n=85 Control group (n=70) Onco female group- patients who have undergone cancer treatment n=60

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: July 15, 2026
• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): January 30, 2029
• Last Updated: July 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share