Clinical trial NCT06030388: Strength and Aerobic Training Against Hot Flushes in Postmenopausal Women
Official title: STrength and AeRobic Training Against Vasomotor Symptoms (START) in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Postmenopausal Symptoms
Hot Flashes
Keywords: aerobic training
strength training
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Region Östergötland
name: Länssjukhuset i Kalmar län
First posted: 2023-09-11
Enrollment: 90
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three-armed randomised trial where participants are randomised to 1) strength training, 2) high-intensity aerobic training or 3) untreated control group.
Primary purpose: TREATMENT

Brief summary: The goal of this randomised controlled trial is to investigate the effects of and compare two modes of physical exercise (strength training and high-intensity aerobic exercise) to unchanged physical activity on vasomotor symptoms (hot flushes) in postmenopausal women. The main question it aims to answer is the effect of 15 weeks of strength training vs high intensity aerobic training vs unchanged physical activity on frequency and severity of hot flushes. Participants will be randomised to:

1. strength training
2. high-intensity aerobic training
3. untreated control group.

Researchers will compare strength training, high-intensity aerobic training and untreated control group to see if training can reduce hot flushes.

Detailed description: The overall aim is to investigate the efficacy of and compare two modes of physical exercise (strength training and high-intensity aerobic exercise) to unchanged physical activity on vasomotor symptoms (VMS), as well as secondary outcomes such as health-related quality of life, sleep quality, physical activity levels, clinical outcomes, biomarkers, bone markers (outcome added January 2025), bone mineral density (outcome added January 2025), perceptions of and adherence to the interventions. In a longer perspective, the goal is to find evidence-based treatment options for VMS in postmenopausal women that are safe and effective, and have positive effects on health and quality of life after menopause.

Our hypothesis is that strength training and high-intensity aerobic exercise will reduce VMS in postmenopausal women and improve quality of life as well as clinical outcomes more than in a control group with unchanged physical activity. We also hypothesize that strength training and high-intensity aerobic training will have the same effect on the primary outcome (change in VMS) and that most of the changes in secondary outcomes will be superior in the high-intensity aerobic training group compared to the strength training group.

This is an open, two-centre, parallel, randomized controlled study performed according to the SPIRIT and CONSORT statements

Recruitment will take place by advertising on social media, in local newspapers and in the Women's clinics and primary care centers in Linköping and Kalmar. Women who respond to the advertisements will be contacted by a member of the research group or research nurse to receive information about the study and screen for inclusion and exclusion criteria. Women who are possibly eligible will be invited to a screening visit for further information and informed consent. At the visit, inclusion and exclusion criteria will be checked by a physician, and a clinical examination will be performed. Eligible participants will receive a VMS screening diary and invited to a second visit 2-3 weeks later where inclusion and randomization will be performed if the VMS inclusion criteria are fulfilled.

Randomization An allocation sequence using a computerized random number generator will be prepared by a statistician not involved in recruitment. Opaque sealed and sequentially numbered envelopes with group allocation will be prepared and opened in the presence of the participant upon inclusion and randomization.

Power analysis: A sample size calculation was made based on the results of our previous study on strength training for VMS (Berin et al 2019) and showed that to detect a 50% difference in moderate and severe hot flushes with 80% power and expected dropout rate of 20% 40 participants in total would be needed. For this three-armed set-up we estimate that 20 participants in each group will be needed, i.e. 60 in total. To also achieve sufficient power for some of the secondary outcomes the intended sample size is increased to 30 per group, 90 in total.

Data analysis: The primary analysis will be performed according to the intention-to-treat principle, including all participants who provided more than baseline data for the primary outcome. For quantitative interval data mixed design ANOVAs will be used to analyze the effect over time between and within groups. For the between-group comparisons effect sizes will be calculated. For ordinal data, such as the questionnaires, Kruskal-Wallis and Friedman test will be used for statistical analysis of the effect. Participants who complete two or more training sessions per week will be considered adherent with their assigned intervention and included in a per-protocol analysis. Detailed description of adherence, such as the fidelity with the training interventions, will be presented descriptively.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women (one of: ≥ 12 months since last menstruation; amenorrhea due to intrauterine device or hysterectomy and Follicle Stimulating Hormone (FSH) \>30 mIU/ml; bilateral oophorectomy; induced menopause due to chemotherapy or radiation and ≥2 years amenorrhea);
* ≥ 28 moderate to severe hot flushes per week during a 2-week screening period, registered through a daily VMS diary;
* Age ≥45 years;
* Physical ability to participate in strength training or high intensity aerobic exercise for 60 minutes, 3 times/week during 15 weeks;
* Understand Swedish orally and in writing

Exclusion Criteria:

* Regular physical activity \>30 minutes per week of vigorous intensity or ≥150 minutes of moderate intensity or combined activities representing maximum 150 minutes of moderate intensity;
* Use of systemic menopausal hormone therapy the last 2 months;
* Use of natural preparations such as herbal preparations for VMS, or other medications for VMS the last 2 months;
* Capillary hemoglobin \<110 g/l;
* Blood pressure \>160 mmHg systolic or \>100 mmHg diastolic;
* Unstable medical condition with a potential to affect VMS (like unregulated thyroid disease);
* Medical condition that by a physician is judged not appropriate (because of potential to affect VMS or risk of injury with vigorous exercise)

Primary outcomes:
measure: Frequency of moderate and severe hot flushes
timeFrame: baseline to 15 weeks
Secondary outcomes:
measure: Frequency of moderate and severe hot flushes
timeFrame: baseline to 6 months, 1, 2 and 5 years
measure: Severity of hot flushes
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years
measure: Generic health-related quality of life
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
measure: Women specific health-related quality of life
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
measure: Physical activity levels
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
measure: Sleep quality
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
measure: Diet
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years
measure: Accomplished physical activity
timeFrame: baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
measure: Bioimpedance
timeFrame: baseline to 15 weeks
measure: Weight
timeFrame: baseline to 15 weeks
measure: Lenght
timeFrame: baseline to 15 weeks
measure: Body mass index
timeFrame: baseline to 15 weeks
measure: Waist circumference
timeFrame: baseline to 15 weeks
measure: Systolic and diastolic blood pressure
timeFrame: baseline to 15 weeks
measure: Hematologic and ironstatus changes
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in blood-lipids
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in sex hormones and gonadotrophins
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in glucose profile
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in inflammatory biomarkers
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in the lenght of telomeres in white blood cells
timeFrame: baseline to 15 weeks, and 1 year
measure: Changes in bone markers
timeFrame: Baseline to 15 weeks, and 1 year
measure: Change in body composition (DXA - dual energy x ray absorptiometry)
timeFrame: Baseline to 15 weeks
measure: Change in bone mineral density (DXA - dual energy x ray absorptiometry)
timeFrame: Baseline to 15 weeks
measure: Change in exercise capacity
timeFrame: baseline to 15 weeks
measure: Experiences of the interventions, facilitators and barriers
timeFrame: baseline to 15 weeks
measure: Adherence to the interventions
timeFrame: baseline to 15 weeks
measure: Muscle strength
timeFrame: baseline to 15 weeks
measure: Adverse events
timeFrame: baseline to 15 weeks
Other outcomes:
Locations:
city: Kalmar
country: Sweden
facility: Region Kalmar Län
city: Linköping
country: Sweden
facility: Region Östergötland
Study officials:
affiliation: Region Östergötland, Linköping university
name: Anna-Clara Spetz Holm, Ass prof, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berin E, Hammar M, Lindblom H, Lindh-Astrand L, Ruber M, Spetz Holm AC. Resistance training for hot flushes in postmenopausal women: A randomised controlled trial. Maturitas. 2019 Aug;126:55-60. doi: 10.1016/j.maturitas.2019.05.005. Epub 2019 May 14.