MenopauseEXISONCT07878741
The Effects of Menopausal Status, Isoflavone Supplementation and Training on Cardiometabolic Function Women
A study testing Red Clover Isoflavone Supplementation and Supervised exercise training in people with Menopause and Exercise Adaptation, run by University of Copenhagen at 2 sites in Denmark.
Trial summary
The goal of this clinical trial is to investigate the role of estrogen and isoflavone supplementation in exercise-induced cellular signaling and cardiometabolic adaptations in premenopausal and postmenopausal women. Read more about this study
- Who is it for?
- Ages 45 to 61 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause, Exercise Adaptation, Mitochondrial Alteration
- What is being tested?
- Red Clover Isoflavone Supplementation and Supervised exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesDenmark
- Study dates
- 15 Oct 2027to 1 Jun 2035
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 61 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women aged ≥45 and <61 years.
- Either *
- *Regular menstrual cycles (premenopausal group), or
- *More than 5 years since the last menstrual period (postmenopausal groups).
- Body mass index (BMI) between 18 and 35 kg/m².
- Able to provide informed consent and comply with study procedures.
Who cannot join
- Current smoking.
- Use of menopausal hormone therapy within the previous 12 months.
- Consumption of isoflavones through diet or supplements within the previous 12 months.
- Chronic disease or medical condition, including diabetes mellitus, cardiovascular disease, polycystic ovary syndrome (PCOS), or endometriosis.
- Active cancer or cancer diagnosis within the previous 5 years.
- Use of medication for hypertension, hypercholesterolemia, diabetes, obesity, or depression.
- Ovariectomy
- Highly physically active lifestyle, defined as more than 3 hours per week of structured moderate-to-vigorous exercise during the previous year, including activities such as running, cycling, or high-intensity team sports.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites
Department of Nutrition, Exercise and Sports
Copenhagen, Storkøbenhavn, 2200
Lasse Gliemann, Associate professor, 004526746624, gliemann@nexs.ku.dk
Lasse Gliemann, Associate professor
Faculty of Medical and Health Sciences
Copenhagen, 2200
Steen Larsen, Associate professor, 004521151924, stelar@sund.ku.dk
Steen Larsen, Associate professor
About this study
Official title: Effekten af Isoflavontilskud og Fysisk træning på Kardiometabolisk Funktion Hos Postmenopausal Kvinder
The goal of this clinical trial is to investigate the role of estrogen and isoflavone supplementation in exercise-induced cellular signaling and cardiometabolic adaptations in premenopausal and postmenopausal women. The study will evaluate vascular function, mitochondrial function, acute and long-term exercise responsiveness, and menopause-related outcomes.
The main questions it aims to answer are:
Read more
- Does menopause alter acute exercise-induced activation of cardiometabolic signaling pathways and vascular function?
- Does isoflavone supplementation enhance exercise-induced improvements in vascular and mitochondrial function in postmenopausal women?
- Are training-induced adaptations in vascular and mitochondrial function different between premenopausal and postmenopausal women?
Researchers will compare postmenopausal women receiving isoflavone supplementation with postmenopausal women receiving placebo to determine the specific effects of isoflavones. Premenopausal women will serve as a reference group to evaluate menopause-related differences.
Participants will:
- Complete an 8-week supervised exercise training intervention consisting of three training sessions per week.
- Undergo assessments of vascular function, including flow-mediated dilation (FMD) and intra-arterial infusions of acetylcholine, epoprostenol, and vitamin C.
- Provide blood and skeletal muscle samples for analyses of cellular signaling pathways, protein expression, and mitochondrial function.
- Undergo measurements of aerobic capacity, strength and body composition.
- Complete questionnaires related to menopause-associated symptoms and health outcomes.
Postmenopausal participants will be randomized to receive either isoflavone supplementation or placebo for 4 weeks prior to and throughout the exercise intervention.
- Conditions
- Menopause, Exercise Adaptation, Mitochondrial Alteration, Vascular Function in Healthy Volunteers
- Being tested
- Red Clover Isoflavone Supplementation, Supervised exercise training, Placebo Supplementation
- Keywords
- Menopause, Vascular function, Mitochondrial function, Training adaptations, Isoflavones, Supplementation, Training intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red Clover Isoflavone SupplementationDietary supplement
Also called Isoflavone
Participants will consume 120 mL/day of red-clover-derived isoflavone supplement, for 4 weeks prior to and throughout an 8-week supervised exercise training intervention (total duration: 12 weeks).
Supervised exercise trainingBehavioural
Also called Training intervention
Participants will complete an 8-week supervised exercise intervention consisting of three 60-minute training sessions per week. The program includes aerobic interval cycling and combined aerobic-resistance circuit training with progressive increases in exercise intensity throughout the intervention period.
Placebo SupplementationDietary supplement
Also called Placebo
Participants will consume 120 mL/day of placebo supplement, for 4 weeks prior to and throughout an 8-week supervised exercise training intervention (total duration: 12 weeks). The placebo beverage is matched in appearance and flavor to the active supplement.
| Study group | Role | What they receive |
|---|---|---|
| Premenopausal women | Experimental | Premenopausal women that will undergo 8 weeks of training (3 times per week). Work as a reference group for the study. Receives: Behavioral: Supervised exercise training |
| Postmenopausal women (placebo) | Placebo comparator | Postmenopausal women who was randomly allocated to placebo supplementation. Work as control group in the study.
They will receive placebo for 4 weeks, and then continue on placebo+training for 8 weeks. Receives: Behavioral: Supervised exercise training; Dietary Supplement: Placebo Supplementation |
| Postmenopausal women (isoflavones) | Experimental | Postmenopausal women who was randomly allocated to isoflavone supplementation. They will receive placebo for 4 weeks, and then continue on isoflavone+training for 8 weeks. Receives: Dietary Supplement: Red Clover Isoflavone Supplementation; Behavioral: Supervised exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive vascular function
Changes in vascular function assessed by intra-arterial acetylcholine and epoprostanol infusion in the brachial artery via ultrasound doppler.
Measured as changes in conductance (ml/min/mmHg)
Measured: Change from week 4 (after supplementation) to week 12 (after exercise plus supplementation)
Invasive vascular function
Changes in vascular function assessed by intra-arterial acetylcholine and epoprostanol infusion in the brachial artery via ultrasound doppler.
Measured as changes in conductance (ml/min/mmHg)
Measured: Change from baseline to week 4 (after supplementation)
Mitochondrial function (skeletal muscle)
Mitochondrial function in skeletal muscle assessed via high resolution respirometry measured in pmol O2/s/mg
Measured: Change from week 4 (after supplementation) to week 12 (after exercise plus supplementation)
Mitochondrial function (skeletal muscle)
Mitochondrial function in skeletal muscle assessed via high resolution respirometry measured in pmol O2/s/mg
Measured: Change from baseline to week 4 (after supplementation)
Exercise induced signaling pathways in skeletal muscle (mitochondrial biogenesis and metabolic adaptation) after acute exercise
Molecular pathways in skeletal muscle involved in exercise adaptation after an acute bout of moderate exercise, including pathways related to energy sensing including AMP-activated protein kinase (AMPK), Mitogen-activated protein kinases (MAPK), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), Mitochondrial transcription factor A (TFAM) and nitric oxide, endothelial nitric oxide synthase (eNOS) signalling measured with transcriptomics, phosphoproteomics, qPCR and western blot. Measurements will be presented as arbitrary units or fold change.
Measured: Baseline (pre acute exercise), immediately after acute exercise, and 3 hours after acute exercise (same study day)
Protein signalling in skeletal muscle
Changes in skeletal muscle expression of protein. Western blots will be used to determine endothelial nitric oxide synthase (eNOS), cyclo-oxygenase 1 and 2, prostacyclin synthase, endothelin receptor A and B, VEGF (vascular endothelial growth factor), Thrombospondin-1, Flk-1 (VEGF receptor), Mitochondrial Transcription Factor A (TFAM). All protein content measures will be presented as arbitrary units.
Measured: Change from baseline to week 4 (after supplementation) to week 12 (after exercise plus supplementation)
Secondary outcomes (5)
Non-invasive vascular function
Changes in vascular function assessed by flow-mediated dilation measured using ultrasound doppler.
Measured as % diameter change from baseline diameter in the resting condition to peak diameter after occlusion.
Measured: Change from week 4 (after supplementation) to week 12 (after exercise plus supplementation)
Non-invasive vascular function
Changes in vascular function assessed by flow-mediated dilation measured using ultrasound doppler.
Measured as % diameter change from baseline diameter in the resting condition to peak diameter after occlusion.
Measured: Change from baseline to week 4 (after supplementation)
Mitochondrial function, ROS production in skeletal muscle
Mitochondrial ROS production measured as H2O2 emission (H2O2/O2 flux) via high resolution fluorometry
Measured: Change from week 4 (after supplementation) to week 12 (after exercise plus supplementation)
Mitochondrial function, ROS production in skeletal muscle
Mitochondrial ROS production measured as H2O2 emission (H2O2/O2 flux) via high resolution fluorometry
Measured: Change from baseline to week 4 (after supplementation)
Acute changes in mitochondrial function
Changes in mitochondrial function (respiration, measured as pmol O2/s/mg) after an acute bout of moderate exercise
Measured: Baseline (pre acute exercise), immediately after acute exercise, and 3 hours after acute exercise (same study day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start15 Oct 2027 (estimated)
- Primary completion1 Jun 2029 (estimated)
- Study completion1 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be assigned to one of three groups: (1) premenopausal women undergoing exercise training only, (2) postmenopausal women receiving placebo supplementation plus exercise training, and (3) postmenopausal women receiving isoflavone supplementation plus exercise training. Postmenopausal participants will receive supplementation for 4 weeks prior to and throughout the 8-week supervised exercise intervention.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lasse Gliemann, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07878741
- Sponsor's protocol ID
- EXISO Study
- Acronym
- EXISO
- Status last verified
- Oct 2026
- First submitted
- 24 Sep 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No