The Alfred Step Test Exercise Protocol (A-STEP), for Adults With Cystic Fibrosis.

Cystic Fibrosis Clinical Trial

— A-STEP  

Official title:

Development; Feasibility/Safety and Validation of the Alfred Step Test Exercise Protocol (A-STEP) Developed for Adults With Cystic Fibrosis:

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02717650
• Other study ID #: 205/16
• Secondary ID: 205/160267
• Status: Recruiting
• Phase: N/A
• Start date: August 25, 2016
• Est. completion date: October 2024

Study information

• Verified date: February 2024
• Source: The Alfred
• Contact: Lisa M Wilson, BHS(Physio)
• Phone: 0390763450
• Email: l.wilson[@]alfred.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Exercise testing has become clinically important in the management and ongoing evaluation of patients with Cystic Fibrosis (CF) with higher rates of exercise tolerance and participation previously linked to lower mortality risk (1).

Lower exercise capacity generally correlates with more severe lung disease (2,3) and landmark studies suggest that low exercise capacity as measured by peak oxygen capacity (VO2peak) and rate of decline in lung function (FEV1) are strong predictors of mortality (1,4). However not all studies have found pulmonary function tests (PFTs) to be reliable predictors of maximal exercise capacity (5), especially in relatively well preserved lung function (6,7).

The wide distribution in physical capacity between fit individuals and end stage disease adds to complexity of assessment. Independent factors of age, genetics, habitual exercise, nutritional status and musculoskeletal conditions are all known to influence physical capacity in patients with CF (8,9).

Maximal exercise testing places additional stress on cardiovascular, respiratory and peripheral systems providing more information around multiple influences on disease progression including degree of limitation in these major systems (10,11) and is useful for assessment of exercise desaturation, more common (but not always present) in advanced lung disease (5,12).

With prediction of exercise performance and functional capacity from PFTs unreliable and the understanding that health status correlates better with exercise tolerance there has been an increase in maximal exercise testing for patient management (13). Many international centers now regard exercise testing as highly important with many assessing maximal exercise capacity annually to monitor disease progression, identify physical status and drive changes in medical, physiotherapy or nutritional management (14,15).

The main vision is to develop a standardized incremental step test protocol suitable for adults with Cystic Fibrosis (CF), all ages, levels of fitness and disease state that is in line with current exercise testing recommendations (15). To develop a more useful field test to assess exercise tolerance and a more "user friendly" test than the currently available laboratory exercise test to allow for early detection of decline in physical function in the day-to-day clinical setting. To date no studies have been published in adults with CF where an incremental exercise step test has been investigated to assess exercise tolerance or determine maximum oxygen uptake (VO2max).

Description:

Many international centers now regard exercise testing as highly important with many measuring maximal exercise capacity annually to monitor disease progression, identify physical status and to drive changes in medical, physiotherapy or nutritional management (14,15).

Cardiopulmonary Exercise Testing (CPET):

The current best practice for assessing VO2max in adults with CF is a CPET using the Godfrey Protocol, a progressive and incremental maximal test performed on a cycle ergometer (13,14,15). Exercise testing should aim to achieve a maximal response within a time frame of 8-12 min and incremental protocols with stage duration of 1 minute are considered more efficient in eliciting the desired response within this time frame (14). During CPET, VO2max is determined while breath-by-breath gas analysis allows for a comprehensive assessment of exercise ventilation and circulation. This information can identify reasons for low exercise capacity and whether exercise limitation is due to deconditioning, or primarily within the respiratory, cardiovascular or peripheral systems. CPET is performed using a specialist ergometer, and requires specialist clinical expertise, monitoring and reporting equipment for interpretation of the test. The cost, space and expertise to carry out CPET in CF units around the world may limit its use for the regular assessment of exercise capacity in adults with CF (16).

Field Tests:

Field tests generally cannot determine absolute maximal exercise capacity, but do provide valuable information about the patient's functional abilities and limitations and compared to laboratory tests are inexpensive and easy to administer.

Field tests that use a single step for assessment of exercise tolerance in patients with chronic lung disease include:

3-Minute Step Test (3MST):

The 3MST is a feasible and acceptable measure of sub-maximal exercise performance in children and adults and a useful tool in the assessment of oxygen desaturation (17,18). The test is short in duration, simple to carry out, and has low cost and minimal space and equipment requirements however the sub-maximal nature and ceiling effect of the 3MST limits its usefulness clinically across the age spectrum (18,19).

The Chester Step Test (CST):

The CST is a 10-minute sub-maximal standardized multistage test and like the 3MST has minimal space and equipment requirements. The CST was originally designed for workplace screening and is now widely used for exercise prescription in the UK cardiac population (20). In healthy individuals one study reported a ceiling effect and a positive relationship between predicted VO2max using the CST and measured VO2max (21) however a subsequent study questioned this prediction validity (22). The CST has been found to be highly reproducible in patients with chronic obstructive lung disease (COPD) and reliable in patients with Bronchiectasis, but too challenging for both groups (23,24).

The Modified Incremental Step Test (MIST):

The MIST was designed to be more suitable for COPD patients and modeled from the CST(25). A reduction in work rate was not found to result in a difference in cardiopulmonary stress and exertion effort at peak exercise but did result in a higher exercise tolerance in patients with COPD. The MIST is reliable and better tolerated than the CST in patients with Bronchiectasis (23,24).

The CST and CF:

One study (published in abstract form) has shown the CST to be a useful field test when compared to the 3MST and 6MWT for those with mild to moderate CF. The authors commented this was likely due to the progressive nature being more representative of adult physical activity (26).

The main vision is to develop a standardized incremental step test protocol suitable for adults with Cystic Fibrosis (CF), all ages, levels of fitness and disease state that is in line with current exercise testing recommendations (15). The test should be a more useful than the already available field tests and more "user friendly" test than the currently available laboratory exercise test to assess exercise tolerance and allow for early detection of decline in physical function in the day-to-day clinical setting. To date no studies have been published in adults with CF where an incremental exercise step test has been investigated to assess exercise tolerance or determine VO2max.

1. To design a standardized externally paced incremental step test that is portable, easy to administer, simple to perform, time, cost and space efficient (A-STEP).

Study A:

2. To assess feasibility and reliability of the A-STEP to objectively assess exercise tolerance.

3. To determine if the A-STEP is a more useful tool than the 3-Minute Step Test.

Study B:

4. To develop an alternative tool to determine maximum oxygen uptake (VO2max) to the "gold standard" CPET that is feasible across the whole spectrum of lung disease.

5. To determine if the A-STEPmax is a valid tool when compared to the VO2max achieved from a CPET performed on a cycle ergometer using the Godfrey Protocol.

The principle investigator hypothesizes that the A-STEP will be a feasible tool to assess exercise capacity; and the A-STEP max will be a valid tool for the assessment of VO2max across the age range and disease spectrum in adults with CF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION

• Confirmed Diagnosis of CF (by genotype or positive sweat test)

• Aged 18yrs and older

• FEV1 =20% (Forced expiration in 1 sec)

• Stable baseline state. (Stable baseline state is defined as: clinically stable respiratory status, for at least 30 days, characterized by the absence of hospitalization and no changes in maintenance therapy during this period (Yankaskas et al 2004)).

EXCLUSION

• Febrile

• Haemoptysis

• Uncontrolled asthma

• Pneumothorax

• Cardiac issues

• Unreliable readings on pulse oximetry

• Pulmonary hypertension

• Unstable CF related diabetes (CFRD)

• Vascular issues

• Renal disease

• Pregnancy

• Body mass index (BMI) <18.0

• Significant musculoskeletal issues

• Unable to safely follow instructions

(ATS/ACCP 2003; Hebestreit 2015)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Genetic Diseases
• Genetic Diseases, Inborn
• Lung Diseases
• Pancreatic Diseases
• Respiration Disorders
• Respiratory Diseases
• Respiratory Tract Diseases

Intervention

Other:
• A-STEP
Study A) Study A) Development of new exercise test protocol and Observational Feasibility/Safety Study (no comparator). Feasibility/safety of a newly designed, incremental, maximal, standardised step test in adults with Cystic Fibrosis.
• A-STEP (New Protocol)
Study B) Validation Study (random allocation of test order). Validity of an incremental, maximal, standardised incremental step test with breath-by-breath gas analysis using portable metabolic measurement equipment against CPET.
• Comparator: CPET cycle ergometer (Gold Standard)
Study B) Validation study (random allocation of test order) "Gold standard" CPET. An incremental, maximal standardised cycle ergometer exercise test (performed as per published protocol) using portable metabolic measurement equipment.

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
The Alfred	Monash University

Country where clinical trial is conducted

Australia, 

References & Publications (27)

American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77. doi: 10.1164/rccm.167.2.211. No abstract available. Erratum In: Am J Respir Crit Care Med. 2003 May 15;1451-2. — View Citation

Andrade CH, Cianci RG, Malaguti C, Corso SD. The use of step tests for the assessment of exercise capacity in healthy subjects and in patients with chronic lung disease. J Bras Pneumol. 2012 Jan-Feb;38(1):116-24. doi: 10.1590/s1806-37132012000100016. English, Portuguese. — View Citation

Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010 Jul 13;122(2):191-225. doi: 10.1161/CIR.0b013e3181e52e69. Epub 2010 Jun 28. No abstract available. — View Citation

Balfour-Lynn IM, Prasad SA, Laverty A, Whitehead BF, Dinwiddie R. A step in the right direction: assessing exercise tolerance in cystic fibrosis. Pediatr Pulmonol. 1998 Apr;25(4):278-84. doi: 10.1002/(sici)1099-0496(199804)25:43.0.co;2-g. — View Citation

Barry SC, Gallagher CG. Corticosteroids and skeletal muscle function in cystic fibrosis. J Appl Physiol (1985). 2003 Oct;95(4):1379-84. doi: 10.1152/japplphysiol.00506.2002. Epub 2003 Jun 13. — View Citation

Buckley JP, Sim J, Eston RG, Hession R, Fox R. Reliability and validity of measures taken during the Chester step test to predict aerobic power and to prescribe aerobic exercise. Br J Sports Med. 2004 Apr;38(2):197-205. doi: 10.1136/bjsm.2003.005389. — View Citation

Camargo AA, Lanza FC, Tupinamba T, Corso SD. Reproducibility of step tests in patients with bronchiectasis. Braz J Phys Ther. 2013 May-Jun;17(3):255-62. doi: 10.1590/s1413-35552012005000089. — View Citation

de Andrade CH, de Camargo AA, de Castro BP, Malaguti C, Dal Corso S. Comparison of cardiopulmonary responses during 2 incremental step tests in subjects with COPD. Respir Care. 2012 Nov;57(11):1920-6. doi: 10.4187/respcare.01742. Epub 2012 Jun 15. — View Citation

de Camargo AA, Justino T, de Andrade CH, Malaguti C, Dal Corso S. Chester step test in patients with COPD: reliability and correlation with pulmonary function test results. Respir Care. 2011 Jul;56(7):995-1001. doi: 10.4187/respcare.01047. — View Citation

Godfrey S, Mearns M. Pulmonary function and response to exercise in cystic fibrosis. Arch Dis Child. 1971 Apr;46(246):144-51. doi: 10.1136/adc.46.246.144. — View Citation

Hebestreit H, Arets HG, Aurora P, Boas S, Cerny F, Hulzebos EH, Karila C, Lands LC, Lowman JD, Swisher A, Urquhart DS; European Cystic Fibrosis Exercise Working Group. Statement on Exercise Testing in Cystic Fibrosis. Respiration. 2015;90(4):332-51. doi: 10.1159/000439057. Epub 2015 Sep 9. — View Citation

Henke KG, Orenstein DM. Oxygen saturation during exercise in cystic fibrosis. Am Rev Respir Dis. 1984 May;129(5):708-11. doi: 10.1164/arrd.1984.129.5.708. — View Citation

Holland AE, Rasekaba T, Wilson JW, Button BM. Desaturation during the 3-minute step test predicts impaired 12-month outcomes in adult patients with cystic fibrosis. Respir Care. 2011 Aug;56(8):1137-42. doi: 10.4187/respcare.01016. Epub 2011 Apr 15. — View Citation

Lands LC, Heigenhauser GJ, Jones NL. Respiratory and peripheral muscle function in cystic fibrosis. Am Rev Respir Dis. 1993 Apr;147(4):865-9. doi: 10.1164/ajrccm/147.4.865. — View Citation

Marcotte JE, Grisdale RK, Levison H, Coates AL, Canny GJ. Multiple factors limit exercise capacity in cystic fibrosis. Pediatr Pulmonol. 1986 Sep-Oct;2(5):274-81. doi: 10.1002/ppul.1950020505. — View Citation

Moorcroft AJ, Dodd ME, Webb AK. Exercise testing and prognosis in adult cystic fibrosis. Thorax. 1997 Mar;52(3):291-3. doi: 10.1136/thx.52.3.291. — View Citation

Narang I, Pike S, Rosenthal M, Balfour-Lynn IM, Bush A. Three-minute step test to assess exercise capacity in children with cystic fibrosis with mild lung disease. Pediatr Pulmonol. 2003 Feb;35(2):108-13. doi: 10.1002/ppul.10213. — View Citation

Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med. 1992 Dec 17;327(25):1785-8. doi: 10.1056/NEJM199212173272504. — View Citation

Nixon PA, Orenstein DM, Kelsey SF. Habitual physical activity in children and adolescents with cystic fibrosis. Med Sci Sports Exerc. 2001 Jan;33(1):30-5. doi: 10.1097/00005768-200101000-00006. — View Citation

Pianosi P, Leblanc J, Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis. Thorax. 2005 Jan;60(1):50-4. doi: 10.1136/thx.2003.008102. — View Citation

Planner, S., Morrison, L., Campbell, J., Bicknell, S., Ross, E. (2007). The Chester Step Test-Is this a Valid Predictor of Disease Severity in Adult CF? . Paper presented at the 2007 Cystic Fibrosis Conference.

Rogers D, Prasad SA, Doull I. Exercise testing in children with cystic fibrosis. J R Soc Med. 2003;96 Suppl 43(Suppl 43):23-9. No abstract available. — View Citation

Shah AR, Gozal D, Keens TG. Determinants of aerobic and anaerobic exercise performance in cystic fibrosis. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1145-50. doi: 10.1164/ajrccm.157.4.9705023. — View Citation

Stevens D, Oades PJ, Armstrong N, Williams CA. A survey of exercise testing and training in UK cystic fibrosis clinics. J Cyst Fibros. 2010 Sep;9(5):302-6. doi: 10.1016/j.jcf.2010.03.004. Epub 2010 Mar 31. — View Citation

Sykes, K., Roberts, A. . (2004). The Chester step test-a simple yet effective tool for the prediction of aerobic capacity. Physiotherapy Theory & Practice, 90(4 ), 183-188 doi: DOI: 10.1016/j.physio.2004.03.008)

Urquhart DS. Exercise testing in cystic fibrosis: why (and how)? J R Soc Med. 2011 Jul;104 Suppl 1(Suppl 1):S6-14. doi: 10.1258/jrsm.2011.s11102. No abstract available. — View Citation

Wilson LM, Ellis MJ, Lane RL, Wilson JW, Keating DT, Jaberzadeh S, Button BM. Development of the A-STEP: A new incremental maximal exercise capacity step test in cystic fibrosis. Pediatr Pulmonol. 2021 Dec;56(12):3777-3784. doi: 10.1002/ppul.25667. Epub 2 — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Study A & B) Gender; Age, Height, BMI, fitness level	Demographic baseline descriptive measures.	Recorded on the day of testing maximum 10 mins.
Other	Study A & B) Spirometry (Pulmonary Function Tests)	Baseline Pulmonary Function Test measures.	Recorded on the day of testing prior to testing, maximum 10 minutes Study B. Most recent PFTs if day of testing lung function is not available study A.
Other	Study A & B) Alfred Wellness Score for CF (AweScore CF)	Alfred specific clinical tools: quality of life measure.	Recorded on the day of testing prior to testing, maximum 2 minutes.
Other	Study A) Musculoskeletal Assessment Tool-Quick Screen	Alfred specific clinical tool: to screen for musculoskeletal issues.	Recorded on the day of testing, maximum 20 minutes.
Other	Study A & B) Medical history.	Baseline descriptive measures of health status.	Recorded on the day of testing, maximum 10 minutes.
Primary	Study B) Maximum oxygen uptake (VO2max)	The highest oxygen uptake achieved during the exercise test taken from inspired gas in a given period of time. Body weight is used to calculate this from oxygen consumption during the test. VO2peak may be used as a surrogate if VO2max is not achieved. Criteria for reaching maximum effort is not included in this document.	Measured during the incremental test for a maximum of 15 minutes.
Primary	Study A) Oxygen Saturation	Standard objective outcome measures of field exercise testing. Measured via pulse oximetry.	Measured for 3 min prior to exercise (recorded at baseline sitting and standing), monitored during the test (recorded at minute intervals) and for at least 2 min of recovery up to a maximum of 10 minutes.
Primary	Study A) Heart Rate	Standard objective outcome measures of field exercise testing. Measured via pulse oximetry.	Measures for 3 min prior to exercise (recorded at baseline sitting and standing), monitored during the test (recorded at minute intervals) and for at least 2 min of recovery up to a maximum of 10 minutes.
Secondary	Study B) Carbon Dioxide Production	Standard secondary outcome measure of maximal exercise testing using breath- by-breath gas analysis with portable metabolic measurement equipment.	Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary	Study B) Respiratory Exchange Ratio	Standard secondary outcome measure of maximal exercise testing using breath- by-breath gas analysis. The ratio of carbon dioxide production to oxygen consumption.	Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary	Study B) Minute Ventilation	Standard secondary outcome measure of maximal exercise testing using breath- by-breath gas analysis. The product of tidal volume and respiratory rate.	Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary	Study B) Oxygen Pulse	Standard secondary outcome measure of maximal exercise testing using breath- by-breath gas analysis. Calculated by dividing the oxygen consumption by heart rate.	Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary	Study B) Tidal Volume	Standard secondary outcome measure of maximal exercise testing using breath- by-breath gas analysis. The volume of each breath taken.	Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary	Study B) Oxygen Saturation	Standard objective outcome measures of exercise testing. Measured via pulse oximetry.	easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary	Study B) Heart rate	Standard objective outcome measures of exercise testing. Measured via pulse oximetry.	easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary	Study B) Measures from Electrocardiogram	Used to monitor the patient's cardiac rhythm (CPET only)	easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary	Study A & B) Breathlessness and Leg Fatigue	Standard subjective outcome measures of exercise testing. Modified Borg 0-10.	Measures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary	Study A & B) Blood pressure	Standard outcome measure of exercise testing.	Measures are takenpre/post A-STEP, pre/every 2 mins during/post CPET
Secondary	Study A & B) Duration of test; Highest level (mins and sec)/stage achieved; Reason for test termination.	Parameters of exercise test.	Measured during or on completion of the test. Maximum 15 minutes.