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

NCT02717650 | Completed

• 2 other identifiers: 205/160267
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Cystic Fibrosis; Fibrosis; Lung Diseases; Respiratory Diseases; Genetic Diseases; Pancreatic Diseases

Keywords

Exercise Testing; Maximal Exercise Testing; Maximal Exercise Capacity; Peak Exercise Capacity; Adults; Step Tests

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (11)

• Study B) Carbon Dioxide Production

  Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.

• Study B) Respiratory Exchange Ratio

  Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.

• Study B) Minute Ventilation

  Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.

• Study B) Oxygen Pulse

  Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.

• Study B) Tidal Volume

  Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.

Other Outcomes (5)

• Study A & B) Gender; Age, Height, BMI, fitness level

  Recorded on the day of testing maximum 10 mins.

• Study A & B) Spirometry (Pulmonary Function Tests)

  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.

• Study A & B) Alfred Wellness Score for CF (AweScore CF)

  Recorded on the day of testing prior to testing, maximum 2 minutes.

Study Arms (3)

A-STEP

EXPERIMENTAL

Study A) A-STEP Study Development of new exercise test protocol and Observational Feasibility/Safety Study (no comparator).

Other: A-STEP

A-STEP (New Protocol)

EXPERIMENTAL

Study B) A-STEPmax Study Validity Study (random allocation of test order).

Other: A-STEP (New Protocol)

CPET cycle ergometer (Gold Standard)

ACTIVE COMPARATOR

Study B) A-STEPmax Study Validity Study (random allocation of test order).

Other: Comparator: CPET cycle ergometer (Gold Standard)

Interventions

A-STEP OTHER

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.

Also known as: Alfred Step Test Exercise Protocol (A-STEP)

A-STEP

A-STEP (New Protocol) OTHER

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.

Also known as: Alfred Step Test Exercise Protocol

A-STEP (New Protocol)

Comparator: CPET cycle ergometer (Gold Standard) OTHER

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.

Also known as: Cardiopulmonary Exercise Test Protocol

CPET cycle ergometer (Gold Standard)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)).

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Alfred: lead
• Monash University: collaborator

Study Sites (1)

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Related Publications (27)

• 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.

  PMID: 1435933 BACKGROUND

• 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.

  PMID: 5576246 BACKGROUND

• 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.

  PMID: 3774384 BACKGROUND

• 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.

  PMID: 15618583 BACKGROUND

• 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.

  PMID: 6426354 BACKGROUND

• 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.

  PMID: 9093351 BACKGROUND

• 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.

  PMID: 9563732 BACKGROUND

• 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.

  PMID: 8466121 BACKGROUND

• 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.

  PMID: 11194108 BACKGROUND

• 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.

  PMID: 12807896 BACKGROUND

• 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.

  PMID: 21719895 BACKGROUND

• 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.

  PMID: 12906322 BACKGROUND

• 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.

  PMID: 12524257 BACKGROUND

• 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.

  PMID: 20585013 BACKGROUND

• Hebestreit H, Arets HGM, Aurora P, Boas S, Cerny F, Hulzebos EHJ, 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):332-351. doi: 10.1159/000439057. Epub 2015 Sep 9.

  PMID: 26352941 BACKGROUND

• 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.

  PMID: 20359963 BACKGROUND

• 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.

  PMID: 9590488 BACKGROUND

• 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.

  PMID: 21496365 BACKGROUND

• 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.

  PMID: 12526071 BACKGROUND

• 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.

  PMID: 22407048 BACKGROUND

• 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)

  BACKGROUND

• 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.

  PMID: 15039259 BACKGROUND

• 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.

  PMID: 21740727 BACKGROUND

• 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.

  PMID: 23966142 BACKGROUND

• 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.

  PMID: 22709990 BACKGROUND

• 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.

  BACKGROUND

• 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 2021 Sep 17.

  PMID: 34499432 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Fibrosis; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Pancreatic Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lisa M Wilson, BHS(Physio)

  Alfred Hospital; Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Physiotherapist

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: March 24, 2016
• Study Start: August 25, 2016
• Primary Completion: March 4, 2024
• Study Completion: March 4, 2024
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)