Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02717650




Registration number
NCT02717650
Ethics application status
Date submitted
10/03/2016
Date registered
24/03/2016
Date last updated
6/02/2024

Titles & IDs
Public title
The Alfred Step Test Exercise Protocol (A-STEP), for Adults With Cystic Fibrosis.
Scientific title
Development; Feasibility/Safety and Validation of the Alfred Step Test Exercise Protocol (A-STEP) Developed for Adults With Cystic Fibrosis:
Secondary ID [1] 0 0
205/16
Secondary ID [2] 0 0
205/16
Universal Trial Number (UTN)
Trial acronym
A-STEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Fibrosis 0 0
Lung Diseases 0 0
Respiratory Diseases 0 0
Genetic Diseases 0 0
Pancreatic Diseases 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - A-STEP
Other interventions - A-STEP (New Protocol)
Other interventions - Comparator: CPET cycle ergometer (Gold Standard)

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

Experimental: A-STEP (New Protocol) - Study B) A-STEPmax Study Validity Study (random allocation of test order).

Active Comparator: CPET cycle ergometer (Gold Standard) - Study B) A-STEPmax Study Validity Study (random allocation of test order).


Other interventions: 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.

Other interventions: 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.

Other interventions: 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.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Study B) Maximum oxygen uptake (VO2max)
Timepoint [1] 0 0
Measured during the incremental test for a maximum of 15 minutes.
Primary outcome [2] 0 0
Study A) Oxygen Saturation
Timepoint [2] 0 0
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 outcome [3] 0 0
Study A) Heart Rate
Timepoint [3] 0 0
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 outcome [1] 0 0
Study B) Carbon Dioxide Production
Timepoint [1] 0 0
Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary outcome [2] 0 0
Study B) Respiratory Exchange Ratio
Timepoint [2] 0 0
Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary outcome [3] 0 0
Study B) Minute Ventilation
Timepoint [3] 0 0
Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary outcome [4] 0 0
Study B) Oxygen Pulse
Timepoint [4] 0 0
Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary outcome [5] 0 0
Study B) Tidal Volume
Timepoint [5] 0 0
Measured during the test incremental tests for a maximum 15 minutes and 5 mins of recovery.
Secondary outcome [6] 0 0
Study B) Oxygen Saturation
Timepoint [6] 0 0
easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary outcome [7] 0 0
Study B) Heart rate
Timepoint [7] 0 0
easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary outcome [8] 0 0
Study B) Measures from Electrocardiogram
Timepoint [8] 0 0
easures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary outcome [9] 0 0
Study A & B) Breathlessness and Leg Fatigue
Timepoint [9] 0 0
Measures are taken at baseline (post 5 mins), monitored during the test (recorded at minute intervals) and for min 5 mins of recovery
Secondary outcome [10] 0 0
Study A & B) Blood pressure
Timepoint [10] 0 0
Measures are takenpre/post A-STEP, pre/every 2 mins during/post CPET
Secondary outcome [11] 0 0
Study A & B) Duration of test; Highest level (mins and sec)/stage achieved; Reason for test termination.
Timepoint [11] 0 0
Measured during or on completion of the test. Maximum 15 minutes.

Eligibility
Key inclusion criteria
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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/08/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The Alfred
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Monash University
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02717650
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Lisa M Wilson, BHS(Physio)
Address 0 0
Alfred Hospital; Monash University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Lisa M Wilson, BHS(Physio)
Address 0 0
Country 0 0
Phone 0 0
0390763450
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02717650