Strength and Aerobic Training Against Hot Flushes in Postmenopausal Women

Hot Flashes Clinical Trial

— START  

Official title:

STrength and AeRobic Training Against Vasomotor Symptoms (START) in Postmenopausal Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06030388
• Other study ID #: START2022-05030-1
• Status: Recruiting
• Phase: N/A
• Start date: September 12, 2023
• Est. completion date: December 2032

Study information

• Verified date: September 2023
• Source: Linkoeping University
• Contact: Anna-Clara Spetz Holm, Ass prof, MD
• Phone: +46101033130
• Email: anna-clara.spetz.holm[@]liu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2032
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hot Flashes
• Postmenopausal Symptoms

Intervention

Other:
• Strength training
Both interventions (strength training and high intensity aerobic training) will be introduced with a 3-week adaptation period with lower loads (strength training) or intensity (aerobic training) followed by a 12-week period on the intended load/intensity. All participants in the intervention groups will be recommended to exercise three times per week (one hour per session) and in addition be active with everyday low-intensity physical activity. A structured and detailed training diary will be used in both groups to register frequency of each training session, as well as everyday physical activity. For the strength training, load and dose will also be registered for each training session.
• High-intensity aerobic training
Both interventions (strength training and high intensity aerobic training) will be introduced with a 3-week adaptation period with lower loads (strength training) or intensity (aerobic training) followed by a 12-week period on the intended load/intensity. All participants in the intervention groups will be recommended to exercise three times per week (one hour per session) and in addition be active with everyday low-intensity physical activity. A structured and detailed training diary will be used in both groups to register frequency of each training session, as well as everyday physical activity. For the strength training, load and dose will also be registered for each training session.

Locations

Country	Name	City	State
Sweden	Region Kalmar Län	Kalmar
Sweden	Region Östergötland	Linköping

Sponsors (3)

Lead Sponsor	Collaborator
Linkoeping University	Länssjukhuset i Kalmar län, Region Östergötland

Country where clinical trial is conducted

Sweden, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of moderate and severe hot flushes	Frequency of hot flushes per 24 h daily recorded in hot flush diary from baseline throughout 15 weeks of intervention.	baseline to 15 weeks
Secondary	Frequency of moderate and severe hot flushes	Frequency of hot flushes per 24 h daily recorded in hot flush diary 2 weeks at baseline and 2 weeks at each of the time points.	baseline to 6 months, 1, 2 and 5 years
Secondary	Severity of hot flushes	Severity of hot flushes per 24 hours recorded in hot flush diary from baseline throughout 15 weeks of intervention and two weeks during follow-up.	baseline to 15 weeks, 6 months, 1, 2 and 5 years
Secondary	Generic health-related quality of life	Short-form 36, 36 questions in 8 scales. Scores for each domain range from 0-100, and a high score represents a higher health-related quality of life.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Secondary	Women specific health-related quality of life	Women's health questionnaire nine sub-scales with four-point scales (yes definitely, yes sometimes, not not much, no not at all) that are reduced to binary options (0/1). The subscale items are summated and divided by the number of items in each subscale.A higher score represents worse outcome.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Secondary	Physical activity levels	International Physical Activity Questionnaire short form, the participant describes the amount of time (minutes and hours) that is spent on different physical activities each week, the more time, the better, except for the question about the amount of time spent in sitting.	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Secondary	Sleep quality	Pittsburgh sleep quality index, 7 domains. For the total instrument, the lower score, the better, from 0 (best) to 21 (worst).	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Secondary	Diet	Bespoke questionnaire, primarily to control for changes during the intervention period. Registration of amounts or portions. Results are presented question by question descriptively.	baseline to 15 weeks, 6 months, 1, 2 and 5 years
Secondary	Accomplished physical activity	Bespoke training diary	baseline to 15 weeks, 6 months, 1, 2 and 5 years after intervention
Secondary	Bioimpedance	Fat mass (%) and fat-free (muscle) mass (%)	baseline to 15 weeks
Secondary	Weight	kilogram (kg)	baseline to 15 weeks
Secondary	Lenght	meters (m)	baseline to 15 weeks
Secondary	Body mass index	kilograms/meters2 (kg/m2)	baseline to 15 weeks
Secondary	Waist circumference	millimeters (mm)	baseline to 15 weeks
Secondary	Systolic and diastolic blood pressure	Unit millimetre of mercury (mmHg)	baseline to 15 weeks
Secondary	Hematologic and ironstatus changes	Hemoglobin full body count, Transferrin(gram/Litre), and Ferritin (microgram/Litre)	baseline to 15 weeks, and 1 year
Secondary	Changes in blood-lipids	apolipoprotein A1, apolipoprotein B (gram/Litre) and total cholesterol, low-density lipoprotein, high-density lipoprotein (mmol/L) and leptin (ng/mL)	baseline to 15 weeks, and 1 year
Secondary	Changes in sex hormones and gonadotrophins	Estradiol (pmol/Litre), Sex hormone bindning globulin, Testosterone (nmol/Litre), follicle-stimulating hormone, luteinizing hormone (IE/Litre)	baseline to 15 weeks, and 1 year
Secondary	Changes in glucose profile	HbA1c (mmol/Litre) and fasting blood glucose (mmol/L)	baseline to 15 weeks, and 1 year
Secondary	Changes in inflammatory biomarkers	high-sensitive C-reactive Protein (microgram/Litre), Brain-derived neutrophic factor, Matrix metalloproteinase-2 and -9 (ng/mL), Interleukin -4, -6, -7, -8, 10, -15, tumour necrosis factor, monocyte chemoattractant protein-1 (pg/mL)	baseline to 15 weeks, and 1 year
Secondary	Changes in the lenght of telomeres in white blood cells	Telomeres (kilobase) pair	baseline to 15 weeks, and 1 year
Secondary	Change in exercise capacity	Change in exercise capacity is primarily used as a measure of adherence and obtained through cardiopulmonary exercise testing assessing maximum oxygen uptake milliliter/kilogram/minute (ml/kg/minute) and analysed according to local clinical routines.	baseline to 15 weeks
Secondary	Experiences of the interventions, facilitators and barriers	Bespoke questionnaire, only for intervention groups. Results will be presented descriptively question by question.	baseline to 15 weeks
Secondary	Adherence to the interventions	Assessed through bespoke training diary where each training session is registered and the total number of training sessions as well as training sessions/week will be calculated.	baseline to 15 weeks
Secondary	Muscle strength	For strength training group only, measured using 8 repetition-maximum tests.	baseline to 15 weeks
Secondary	Adverse events	Adverse events of taking part in the study	baseline to 15 weeks