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Asthma Severity in Women: The Influence of Training and Menopause (ATOM)

Primary Purpose

Late-Onset Asthma

Status
Terminated
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Aerobic exercise
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Late-Onset Asthma

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Respiratory research unit, Bispebjerg University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Aerobic exercise intervention

Control group

Arm Description

Aerobic exercise by high intensity interval training, 3 times per week for 12 weeks

No intervention for 12 weeks

Outcomes

Primary Outcome Measures

Asthma control - Asthma Control Questionnaire (ACQ)
Changes in Asthma Control Questionnaire (ACQ) 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use)

Secondary Outcome Measures

Heart Rate Variability
Changes in: - Heart rate variability
Heart rhytm
Changes in: - Heart rhythm
Heart Rate
Changes in: - electrocardiography
Heart function - Strain
Measured by stress-echocardiography - Strain
Heart function - Ejection fraction
Measured by stress-echocardiography - Ejection fraction
Heart function - Tricuspid annular plane systolic excursion
Measured by stress-echocardiography - Tricuspid annular plane systolic excursion
Heart function - Right ventricular function
Measured by stress-echocardiography - Right ventricular function
Heart function - Pulmonary pressure
Measured by stress-echocardiography - Pulmonary pressure
Heart function - Lung covered cor
Measured by stress-echocardiography - Lung covered cor
Heart function - Blood pressure
Blood pressure
Heart function - Cardiac output
Cardiac output
Heart function - Stroke volume
Stroke volume
Heart function - Total peripheral resistance
Total peripheral resistance
Systemic inflammation - Leukocytes + differential cell count count
Changes in - Leukocytes + differential cell count count
Systemic inflammation - Interleukin 6
Changes in - Interleukin 6
Systemic inflammation - Interleukin 8
Changes in - Interleukin 8
Systemic inflammation
Changes in - Other interleukins
Systemic inflammation - Tumor Necrosis Factor alpha
Changes in - Tumor Necrosis Factor alpha
Systemic inflammation - Total immunoglobulin E, Specific immunoglobulin E
Changes in Total immunoglobulin E Specific immunoglobulin E
Systemic inflammation - high sensitivity c reactive protein
Changes in - high sensitivity c reactive protein
Local airway inflammation - Sputum cell count
Changes in - Sputum cell count
Local airway inflammation - Fraction of exhaled nitric oxide
Changes in - Fraction of exhaled nitric oxide
Local airway inflammation - Hyperreactivity to inhaled methacholine
Changes in - Hyperreactivity to inhaled methacholine
Body Composition
Changes in - Total body fat
Body Composition
Changes in - Lean body mass
Body Composition
Changes in - Muscle mass
Body Composition
Changes in - Weight
Microbiome
Changes in the microbiota in sputum, oral cavity and nasal cavity before and after the training intervention
Compliance - Foster score
Change in - Foster score Answers describe last weeks medicine use. Answers range form 0/7 - 7/7 with low values being worse.
Other asthma related questionnaires - Nijmegen questionnaire
Changes in - Nijmegen questionnaire Values range from 0-64 and values below 20 are considered normal.
Other asthma related questionnaires - Mini Asthma Quality of Life Questionnaire (miniAQLQ)
Changes in - Mini Asthma Quality of Life Questionnaire (miniAQLQ) 7-point Likert scale (7 = not impaired at all - 1 = severely impaired).
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)
Changes in - Hospital Anxiety and Depression Scale (HADS)

Full Information

First Posted
November 9, 2018
Last Updated
June 17, 2021
Sponsor
Rigshospitalet, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT03747211
Brief Title
Asthma Severity in Women: The Influence of Training and Menopause
Acronym
ATOM
Official Title
The ATOM Study: Asthma Severity in Women: The Influence of Training and Menopause
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Issues recruiting participants during COVID-19
Study Start Date
February 12, 2019 (Actual)
Primary Completion Date
May 1, 2021 (Actual)
Study Completion Date
May 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Late-Onset Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized, outcome assessor blinded, controlled trial
Masking
InvestigatorOutcomes Assessor
Masking Description
Concealed computer generated allocation via REDCap
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aerobic exercise intervention
Arm Type
Experimental
Arm Description
Aerobic exercise by high intensity interval training, 3 times per week for 12 weeks
Arm Title
Control group
Arm Type
No Intervention
Arm Description
No intervention for 12 weeks
Intervention Type
Behavioral
Intervention Name(s)
Aerobic exercise
Intervention Description
High Intensity Interval Training (HIIT)
Primary Outcome Measure Information:
Title
Asthma control - Asthma Control Questionnaire (ACQ)
Description
Changes in Asthma Control Questionnaire (ACQ) 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use)
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Secondary Outcome Measure Information:
Title
Heart Rate Variability
Description
Changes in: - Heart rate variability
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart rhytm
Description
Changes in: - Heart rhythm
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart Rate
Description
Changes in: - electrocardiography
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Strain
Description
Measured by stress-echocardiography - Strain
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Ejection fraction
Description
Measured by stress-echocardiography - Ejection fraction
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Tricuspid annular plane systolic excursion
Description
Measured by stress-echocardiography - Tricuspid annular plane systolic excursion
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Right ventricular function
Description
Measured by stress-echocardiography - Right ventricular function
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Pulmonary pressure
Description
Measured by stress-echocardiography - Pulmonary pressure
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Lung covered cor
Description
Measured by stress-echocardiography - Lung covered cor
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Blood pressure
Description
Blood pressure
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Cardiac output
Description
Cardiac output
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Stroke volume
Description
Stroke volume
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Heart function - Total peripheral resistance
Description
Total peripheral resistance
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - Leukocytes + differential cell count count
Description
Changes in - Leukocytes + differential cell count count
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - Interleukin 6
Description
Changes in - Interleukin 6
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - Interleukin 8
Description
Changes in - Interleukin 8
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation
Description
Changes in - Other interleukins
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - Tumor Necrosis Factor alpha
Description
Changes in - Tumor Necrosis Factor alpha
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - Total immunoglobulin E, Specific immunoglobulin E
Description
Changes in Total immunoglobulin E Specific immunoglobulin E
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Systemic inflammation - high sensitivity c reactive protein
Description
Changes in - high sensitivity c reactive protein
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Local airway inflammation - Sputum cell count
Description
Changes in - Sputum cell count
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Local airway inflammation - Fraction of exhaled nitric oxide
Description
Changes in - Fraction of exhaled nitric oxide
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Local airway inflammation - Hyperreactivity to inhaled methacholine
Description
Changes in - Hyperreactivity to inhaled methacholine
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Body Composition
Description
Changes in - Total body fat
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Body Composition
Description
Changes in - Lean body mass
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Body Composition
Description
Changes in - Muscle mass
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Body Composition
Description
Changes in - Weight
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Microbiome
Description
Changes in the microbiota in sputum, oral cavity and nasal cavity before and after the training intervention
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Compliance - Foster score
Description
Change in - Foster score Answers describe last weeks medicine use. Answers range form 0/7 - 7/7 with low values being worse.
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Other asthma related questionnaires - Nijmegen questionnaire
Description
Changes in - Nijmegen questionnaire Values range from 0-64 and values below 20 are considered normal.
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
Other asthma related questionnaires - Mini Asthma Quality of Life Questionnaire (miniAQLQ)
Description
Changes in - Mini Asthma Quality of Life Questionnaire (miniAQLQ) 7-point Likert scale (7 = not impaired at all - 1 = severely impaired).
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention
Title
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)
Description
Changes in - Hospital Anxiety and Depression Scale (HADS)
Time Frame
-21 to 0 days before intervention and 0 to 14 days post intervention

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vibeke Backer, Physician
Organizational Affiliation
Respiratory Research Unit, Bispebjerg Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Respiratory research unit, Bispebjerg University Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data that support the results of this study will be made available immediately, with no end date, after deidentification and upon reasonable request.
IPD Sharing Time Frame
Immediately after publication with no end date.
IPD Sharing Access Criteria
Data will be made available upon reasonable request to achieve the aims of the reasonable request.
Citations:
PubMed Identifier
33888532
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.
Results Reference
derived

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Asthma Severity in Women: The Influence of Training and Menopause

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