Clinical trial NCT03747211: Asthma Severity in Women: The Influence of Training and Menopause
Official title: The ATOM Study: Asthma Severity in Women: The Influence of Training and Menopause
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Late-Onset Asthma
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2018-11-20
Enrollment: 12
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, outcome assessor blinded, controlled trial
Primary purpose: TREATMENT

Brief summary: Introduction: Late-onset asthma in women is characterized by poor disease control and reduced quality of life despite intensive treatment with inhaled steroid and beta2-agonist. The condition is further worsened at menopause due to the loss of estrogen leading to increased asthma exacerbation frequency, increased airway inflammation and decreased lung function. Exercise training may increase disease control of asthma patients, but to what extent the same effect is seen in postmenopausal women with late-onset asthma is unknown. These asthma patients represent a phenotype that is characterized by low eosinophilic airway inflammation, severe symptoms, moderate obesity and poor response to conventional medicine. Thus, our hypothesis is that regular physical exercise is especially associated with an improvement in asthma control in this phenotype. The aim of this project is to test this hypothesis and to assess whether an improvement is associated with reduced local and systemic inflammation, change in heart function, lung function and/or body composition.

Study design: 40 postmenopausal women with late-onset asthma are recruited via the outpatient clinic at the Respiratory Department at Bispebjerg Hospital and through advertisement. The participants are randomized 1:1 into two groups. One group performs supervised exercise training (spinning) three times per week for 12 weeks while the other group is a control group. Before and after the intervention asthma control, local and systemic inflammation, heart function and body composition is measured.

Results: Analysis will be performed to detect changes within and between the groups before and after intervention. Primary outcome is change in ACQ (Asthma Control Questionnaire). Local and systemic inflammation is measured by changes in bronchial challenge to methacholine, sputum cell count and blood tests. Furthermore, secondary outcomes include change in heart function measured by stress-echocardiography and change in body composition measured by Dual-energy X-ray absorptiometry (DEXA).

Conclusion: There are to date no prospective studies that can support recommendations containing asthma rehabilitation with supervised regular physical activity for postmenopausal women. Thus, this study will provide novel understanding of the importance of physical activity in a chronic disease such as asthma.

Detailed description: Overall study design

The study is a single-blinded randomized controlled intervention study. Forty postmenopausal women with late-onset asthma (\>16 years at debut) are recruited from the asthma outpatient-clinic at Bispebjerg Hospital or other hospital/practitioner in the region and/or by advertisement. The participants are block-randomized into two groups of 20, where one group is control and the other undergoes a period of regular exercise training. The investigators will be blinded and will not know whether the subjects have trained or not.

Detailed study design

Participants allocated to the exercise training group undergo a training intervention consisting of 45 minutes of intermittent high intensity aerobic spinning training three times per week for 12 weeks. Participants allocated to the control group will continue usual care without training. No changes to current treatment will be made by the investigators on any of the groups.

The training will consist of short periods of high intensity intervals where subjects reach above 80% of maximal oxygen consumption. Spinning sessions will be fully supervised by trained instructors with a bachelor of sports and science or bachelor of medicine and conducted in the Department of Nutrition, Exercise and Sports, University of Copenhagen. Subjects will wear heart rate monitors to ensure adherence to the training protocol. Within two weeks, before and after the intervention, participants from both groups undergo 3 days of testing.

To ensure equal compliance with asthma medication both groups will receive daily electronic reminders. Once a week, all participants will be asked about their compliance to their medication.

Eligibility criteria: Inclusion Criteria:

* Late onset asthma (Debut ≥ 16 years of age)
* ACQ ≥ 1.25
* Daily treatment for asthma (GINA 2 and above)
* Age 45 - 75
* Postmenopausal defined as no menstruation for 6 months, Serum Follicle stimulating hormone \>20 International Units per Liter and P-Estradiol nmol/L \<0.09
* BMI 25 - 35
* Positive bronchial challenge to methacholine, mannitol or positive reversibility to beta2-agonist now or historically
* Untrained (no participation in vigorous exercise for more than 1 hour per week during the last 2 months)
* Capable of exercising on a bike

Exclusion Criteria:

* Unable to speak and understand Danish or English.
* Current or former smokers (\>6 months cessation) with \>20 years of daily smoking with 20 cigarettes per day.
* Other respiratory disease of clinical significance
* Cardiovascular: Unstable ischemic heart disease, myocardial infarction within the last 12 months, symptomatic heart failure (EF \<40%), symptomatic heart arrhythmia (documented with ECG), uncontrolled hypertension (\>155/100)
* Any disorder that is not stable and in the opinion of the investigator could affect the safety of the subject throughout the study
* Subjects, who by investigators determination, will not be able to adhere to study protocol

Primary outcomes:
measure: Asthma control - Asthma Control Questionnaire (ACQ)
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
Secondary outcomes:
measure: Heart Rate Variability
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart rhytm
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart Rate
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Strain
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Ejection fraction
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Tricuspid annular plane systolic excursion
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Right ventricular function
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Pulmonary pressure
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Lung covered cor
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Blood pressure
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Cardiac output
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Stroke volume
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Heart function - Total peripheral resistance
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - Leukocytes + differential cell count count
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - Interleukin 6
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - Interleukin 8
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - Tumor Necrosis Factor alpha
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - Total immunoglobulin E, Specific immunoglobulin E
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Systemic inflammation - high sensitivity c reactive protein
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Local airway inflammation - Sputum cell count
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Local airway inflammation - Fraction of exhaled nitric oxide
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Local airway inflammation - Hyperreactivity to inhaled methacholine
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Body Composition
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Body Composition
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Body Composition
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Body Composition
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Microbiome
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Compliance - Foster score
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Other asthma related questionnaires - Nijmegen questionnaire
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Other asthma related questionnaires - Mini Asthma Quality of Life Questionnaire (miniAQLQ)
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
measure: Other asthma related questionnaires - Hospital Anxiety and Depression Scale (HADS) 2 items with 7 questions regarding anxiety and depression. (0 = no sign of depression/anxiety, 21 = maximal signs of anxiety/depression)
timeFrame: -21 to 0 days before intervention and 0 to 14 days post intervention
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Respiratory research unit, Bispebjerg University Hospital
Study officials:
affiliation: Respiratory Research Unit, Bispebjerg Hospital
name: Vibeke Backer, Physician
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hansen ESH, Hostrup M, Rasmusen HK, Hellsten Y, Backer V. Effect of aerobic exercise training on asthma control in postmenopausal women (the ATOM-study): protocol for an outcome assessor, randomised controlled trial. BMJ Open. 2021 Apr 22;11(4):e049477. doi: 10.1136/bmjopen-2021-049477.