Clinical trial NCT04711057: CENTR(AR): Lungs Moving
Official title: CENTR(AR): Lungs Moving
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Respiratory Disease
Lung Diseases
Pulmonary Disease
Chronic Obstructive Pulmonary Disease
Interstitial Lung Disease
Keywords: Chronic Respiratory Disease
Pulmonary Rehabilitation
Physical Activity
Behavioral Change
Lead sponsor: Aveiro University
Sponsor class: OTHER
Collaborators: name: Programa Operacional Inclusão Social e Emprego (POISE)
name: Programa Operacional Competitividade e Internacionalização (POCI) - Compete2020
name: Portuguese National Funding Agency for Science, Research and Technology (FCT)
name: Aveiro Institute of Biomedicine (iBiMED)
name: School of Health Sciences, University of Aveiro (ESSUA)
name: City Council/Municipality: a) Aveiro; b) Estarreja; c) Oliveira do Bairro; d) Montemor-o-Velho
name: Administração Regional de Saúde do Centro, IP (ARS Centro)
name: Centro Hospitalar do Baixo Vouga (CHBV), E.P.E.
First posted: 2021-01-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic Respiratory Diseases (CRDs) are associated with substantial morbidity and mortality, ranking as the third leading cause of death worldwide. Pulmonary rehabilitation (PR) is a fundamental evidence-based intervention for the management of a variety of CRDs, such as Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Diseases (ILDs). However, the benefits of PR tend to decline over time and there is currently no strong evidence that patients translate those benefits into a more active lifestyle. There is an urgent need for evidence-based interventions to promote physical activity (PA) participation, whilst maintaining PR positive effects in the long-term. Community-based PA interventions adjusted to the local context, as well as patients' needs and preferences, might be a key strategy to meet this target. CENTR(AR) will be a sustainable response to support healthy lifestyles and enhance long-term PR benefits, by providing access to PR within Primary Healthcare Centres (PHC), followed by the inclusion in a community-based PA program, which embraces urban facilities and available resources.

Detailed description: The Global Burden Disease Study 2017 estimated that 544.9 million people worldwide had a chronic respiratory disease (CRD). Globally, it is estimated that 3.914.196 deaths were due to CRDs in 2017, accounting for 7% of total all-cause deaths, ranking CRDs as the third leading cause of death worldwide. Pulmonary rehabilitation (PR) is a well-established, cost-effective intervention for the management of CRDs (e.g., COPD, ILD), which has been found to improve exercise capacity, dyspnoea and quality of life. Unfortunately, PR remains an underutilized resource in the community. Despite substantial improvement following PR, benefits tend to decline over time (approximately, within a 12-month period) and there is currently no strong evidence that patients translate those benefits into a more active lifestyle. This is of utmost importance since physical activity (PA) levels predict important outcomes in COPD, for example, with low PA levels being associated with a higher risk of exacerbation-related hospitalization and mortality. That said, it is still unknown how best to maintain long-term effects of PR, whilst promoting patients' adherence to a physically active lifestyle. Most studies reporting on interventions to improve PA among patients with CRDs (e.g., COPD) focus exclusively on patients' individual factors, disregarding interpersonal/social and environmental factors associated with PA. Community-based PA interventions adjusted to the local context, which leverage existing social support and community (infra)structures, may be key elements for success. Indeed, the community offers a variety of physical activity modalities (e.g., urban trails, physical activity/exercise classes at the municipality level), which can be explored and further personalized to meet patients' needs and preferences. By targeting the community, as opposed to the "individual per se", the possibility of promoting a behavioral change towards a more physically active lifestyle becomes more likely. Building on existing knowledge, CENTR(AR) primary aim is to implement and assess the effectiveness of a personalised community-based PA program to increase PA levels, as well as prevent/stop the decline and consolidate PR benefits (in several health-related domains) in people with CRDs, following PR.

Additionally, CENTR(AR) will also aim at:

1) Improving access to and delivery of community-based PR for people with CRDs in Primary Healthcare Centres (PHC) within the Centre Region of Portugal; 2) Identifying barriers and facilitators, as well as preferences and motivations of adherence to PA; 3) Educating/Empowering/Capacitating non-health professionals delivering municipal physical activity/exercise classes, to ensure patients' safety and quality care; 4) Designing and validating urban walking and/or cycling trails by a) measuring the physiological response and energy expenditure associated with the use of those trails; b) assessing the environmental/physical features of the urban trails; 5) Validating the available municipal physical activity/exercise classes (as described in 3); 6) Promoting intersectoral collaboration at the municipality level, leveraging partnerships between PHC and existing community physical activities, thereby filling in the gaps in the continuity of care after PR; 7) Increasing health literacy amongst municipal professionals in regard to CRDs, as well as health promotion and community empowerment.

Randomized Controlled Trial (RCT)

Aims \& Outcomes Primary aim: Assess the effectiveness of a community-based PA program, tailored to patient's needs and preferences, to increase PA levels in people with CRDs.

Secondary aim(s): Determine the short-, mid- and long-term effects of CENTR(AR) on exercise capacity, functional status, HRQoL, symptoms, AECOPD and healthcare utilisation, peripheral muscle strength, motivation for exercise, and emotional status; Establish the influence of patients' motivations and preferences in adhering to the CENTRAR program and engaging in a physically active lifestyle.

At each time-point, the following data will be collected: Socio-demographic and anthropometric data; Lung function; Healthcare utilization; Health-related quality of life (HRQoL); Impact of disease; Fatigue; Dyspnoea; Cough and sputum; Social support and social network; Anxiety and depression; Motivation to exercise; Perception of change; Exercise capacity; Peripheral muscle strength; Functional status; Balance; Physical activity levels; Adverse events; Adherence; Qualitative data (individual and focus groups interviews)

Study Design \& Intervention

After completion of PR, participants will be randomised to an experimental group (EG) or a control group (CG). The EG will enrol in a 6-month personalised community-based PA program, which will/should be attended twice-weekly, minimum. During the first month the physiotherapist will guide patients through all available physical activities; afterwards, patients will be asked to choose one or two activities, according to their preferences, which they will attend for five more months. Physiotherapists' support will gradually decrease over time. The CG will receive a leaflet with PA recommendations.

Sample Size Estimation

The sample size was estimated using G\*Power 3.1.9.6, with an effect size specification "as in G\*Power 3.0", for the within-between interaction of a repeated measures ANOVA with two groups (control and experimental) and 3 measurements (immediately after, and 6 to 12 months post-PR) of the defined primary outcome (MVPA). The investigators considered an α of 0.05, a power of 0.80, a repeated measures correlation of 0.5, a nonsphericity correction of 1 and an expected effect size f of 0.30. The effect size f was derived from the partial η2 of 0.21 (f=0.516) obtained from a study which aimed to assess the impact of a PA-focused behavioural intervention during and after PR on PA levels in patients with COPD. A smaller f value of 0.30 was chosen to account for a longer follow-up period (up to 12 months) and differences in selected time-points. The calculated sample size was 20 (i.e., 10 in each group) COPD patients and considering a possible 50% dropout rate, the final sample size was determined to be 40. Since no significant differences are expected in the primary outcome between COPD and ILD patients, a sample size of 40 was also determined for the latter. In summary, a total sample size of 80 was found to be required to detect significant within-between group differences in MVPA.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of a chronic respiratory disease;
* Stable clinical condition (defined as no acute exacerbation or hospitalization in the previous month).

Exclusion Criteria:

* Signs of cognitive impairment;
* Neoplasic/Immunologic disease or an unstable/significant cardiac (e.g., exertional angina, valvular heart disease, congestive heart failure, etc.), musculoskeletal/orthopaedic, neuromuscular or psychiatric condition limiting ability to exercise or co-operate.

Primary outcomes:
measure: Change in PA levels (time spent in moderate to vigorous physical activity (MVPA))
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
Secondary outcomes:
measure: Change in PA levels (time spent in sedentary behaviour)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in step count (steps/day-1)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in health-related quality of life (HRQoL) - St. George Respiratory Questionnaire
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in exercise capacity/tolerance - 6-minute walk test (6MWT)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in overall functional status/physical function - Physical Performance Test
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in quadriceps muscle strength - Isometric dynamometry
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in handgrip strength - Isometric dynamometry
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Healthcare utilisation - AECOPD frequency (previous year)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Healthcare utilisation - Emergency department visits (number of visits per participant)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in healthcare utilization - Hospital (re)admissions (number of hospital admissions per participant)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in healthcare utilization - Hospital (re)admissions (length of stay per hospital admission)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in motivation to exercise - The Behavioural Regulation Exercise Scale-2 (BREQ-2)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in PA levels - Brief Physical Activity Questionnaire
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in impact of symptoms - COPD Assessment Test (CAT)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in emotional status - Hospital Anxiety and Depression Scale (HADS)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in subjective experience of fatigue - Checklist of Individual Strength - Fatigue subscale
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in impact of fatigue - Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in impact of cough and sputum - Cough and Sputum Assessment Questionnaire (CASA-Q)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in exercise tolerance/capacity and (lower limb) functional capacity - 1-minute sit-to-stand test
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in perceived social support - six-item Social Support Questionnaire (SSQ6)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Change in peripheral muscle strength (one- (1RM) or ten- (10RM) repetition maximum)
timeFrame: before PR (T0), immediately after PR (T1), and after a 3, 6 and 12 month-period.
measure: Quality trail experience
timeFrame: Immediately after PR
measure: Adherence to the physical activity programme
timeFrame: Adherence will be collected in each session of physical activity throughout the 6 months.
measure: Occurrence of adverse events
timeFrame: Occurrence of an adverse event will be collected in each session of physical activity throughout the 6 months
Other outcomes:
Locations:
city: Aveiro
country: Portugal
facility: School of Health Sciences of the University of Aveiro (ESSUA)
Study officials:
affiliation: School of Health Sciences, University of Aveiro (ESSUA)
name: Alda S. Marques, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: GBD Chronic Respiratory Disease Collaborators. Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020 Jun;8(6):585-596. doi: 10.1016/S2213-2600(20)30105-3.
citation: McCarthy B, Casey D, Devane D, Murphy K, Murphy E, Lacasse Y. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015 Feb 23;2015(2):CD003793. doi: 10.1002/14651858.CD003793.pub3.
citation: Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev. 2014 Oct 6;(10):CD006322. doi: 10.1002/14651858.CD006322.pub3.
citation: Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, Hill K, Holland AE, Lareau SC, Man WD, Pitta F, Sewell L, Raskin J, Bourbeau J, Crouch R, Franssen FM, Casaburi R, Vercoulen JH, Vogiatzis I, Gosselink R, Clini EM, Effing TW, Maltais F, van der Palen J, Troosters T, Janssen DJ, Collins E, Garcia-Aymerich J, Brooks D, Fahy BF, Puhan MA, Hoogendoorn M, Garrod R, Schols AM, Carlin B, Benzo R, Meek P, Morgan M, Rutten-van Molken MP, Ries AL, Make B, Goldstein RS, Dowson CA, Brozek JL, Donner CF, Wouters EF; ATS/ERS Task Force on Pulmonary Rehabilitation. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013 Oct 15;188(8):e13-64. doi: 10.1164/rccm.201309-1634ST.
citation: Spruit MA, Pitta F, McAuley E, ZuWallack RL, Nici L. Pulmonary Rehabilitation and Physical Activity in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 Oct 15;192(8):924-33. doi: 10.1164/rccm.201505-0929CI.
citation: Gimeno-Santos E, Frei A, Steurer-Stey C, de Batlle J, Rabinovich RA, Raste Y, Hopkinson NS, Polkey MI, van Remoortel H, Troosters T, Kulich K, Karlsson N, Puhan MA, Garcia-Aymerich J; PROactive consortium. Determinants and outcomes of physical activity in patients with COPD: a systematic review. Thorax. 2014 Aug;69(8):731-9. doi: 10.1136/thoraxjnl-2013-204763. Epub 2014 Feb 20.
citation: Burge AT, Cox NS, Abramson MJ, Holland AE. Interventions for promoting physical activity in people with chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2020 Apr 16;4(4):CD012626. doi: 10.1002/14651858.CD012626.pub2.
citation: Mantoani LC, Rubio N, McKinstry B, MacNee W, Rabinovich RA. Interventions to modify physical activity in patients with COPD: a systematic review. Eur Respir J. 2016 Jul;48(1):69-81. doi: 10.1183/13993003.01744-2015. Epub 2016 Apr 21.
citation: Robinson H, Williams V, Curtis F, Bridle C, Jones AW. Facilitators and barriers to physical activity following pulmonary rehabilitation in COPD: a systematic review of qualitative studies. NPJ Prim Care Respir Med. 2018 Jun 4;28(1):19. doi: 10.1038/s41533-018-0085-7.
citation: Arbillaga-Etxarri A, Gimeno-Santos E, Barberan-Garcia A, Balcells E, Benet M, Borrell E, Celorrio N, Delgado A, Jane C, Marin A, Martin-Cantera C, Monteagudo M, Montella N, Munoz L, Ortega P, Rodriguez DA, Rodriguez-Roisin R, Simonet P, Toran-Monserrat P, Torrent-Pallicer J, Vall-Casas P, Vilaro J, Garcia-Aymerich J. Long-term efficacy and effectiveness of a behavioural and community-based exercise intervention (Urban Training) to increase physical activity in patients with COPD: a randomised controlled trial. Eur Respir J. 2018 Oct 18;52(4):1800063. doi: 10.1183/13993003.00063-2018. Print 2018 Oct.
citation: Cruz J, Brooks D, Marques A. Walk2Bactive: A randomised controlled trial of a physical activity-focused behavioural intervention beyond pulmonary rehabilitation in chronic obstructive pulmonary disease. Chron Respir Dis. 2016 Feb;13(1):57-66. doi: 10.1177/1479972315619574. Epub 2015 Dec 23.
citation: Wootton SL, Hill K, Alison JA, Ng LWC, Jenkins S, Eastwood PR, Hillman DR, Jenkins C, Spencer LM, Cecins N, McKeough ZJ. Effects of Ongoing Feedback During a 12-Month Maintenance Walking Program on Daily Physical Activity in People with COPD. Lung. 2019 Jun;197(3):315-319. doi: 10.1007/s00408-019-00216-5. Epub 2019 Apr 15.
citation: Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. 1991 Sep;85 Suppl B:25-31; discussion 33-7. doi: 10.1016/s0954-6111(06)80166-6.
citation: Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, McCormack MC, Carlin BW, Sciurba FC, Pitta F, Wanger J, MacIntyre N, Kaminsky DA, Culver BH, Revill SM, Hernandes NA, Andrianopoulos V, Camillo CA, Mitchell KE, Lee AL, Hill CJ, Singh SJ. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014 Dec;44(6):1428-46. doi: 10.1183/09031936.00150314. Epub 2014 Oct 30.
citation: Reuben DB, Siu AL. An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc. 1990 Oct;38(10):1105-12. doi: 10.1111/j.1532-5415.1990.tb01373.x.
citation: O'Shea SD, Taylor NF, Paratz JD. Measuring muscle strength for people with chronic obstructive pulmonary disease: retest reliability of hand-held dynamometry. Arch Phys Med Rehabil. 2007 Jan;88(1):32-6. doi: 10.1016/j.apmr.2006.10.002.
citation: Markland, D. and V. Tobin, A Modification to the Behavioural Regulation in Exercise Questionnaire to Include an Assessment of Amotivation. 2004. 26(2): p. 191.
citation: Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
citation: Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
citation: Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage. 1997 Feb;13(2):63-74. doi: 10.1016/s0885-3924(96)00274-6.
citation: Crawford B, Monz B, Hohlfeld J, Roche N, Rubin B, Magnussen H, Nivens C, Ghafouri M, McDonald J, Tetzlaff K. Development and validation of a cough and sputum assessment questionnaire. Respir Med. 2008 Nov;102(11):1545-55. doi: 10.1016/j.rmed.2008.06.009. Epub 2008 Jul 27.
citation: Ozalevli S, Ozden A, Itil O, Akkoclu A. Comparison of the Sit-to-Stand Test with 6 min walk test in patients with chronic obstructive pulmonary disease. Respir Med. 2007 Feb;101(2):286-93. doi: 10.1016/j.rmed.2006.05.007. Epub 2006 Jun 27.
citation: Sarason, I.G., et al., A Brief Measure of Social Support: Practical and Theoretical Implications. Journal of Social and Personal Relationships, 1987. 4(4): p. 497-510.