Investigation of the Effects of Pulmonary Rehabilitation in Children With Primary Immunodeficiency

Primary Immunodeficiency Clinical Trial

Official title:

Investigation of the Effects of Pulmonary Rehabilitation on Exercise Capacity, Muscle Oxygenation and Physical Activity Level in Children With Primary Immunodeficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06092528
• Other study ID #: Gazi University 73
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: September 20, 2026

Study information

• Verified date: December 2023
• Source: Gazi University
• Contact: Meral Bosnak Güçlü, Prof. Dr.
• Phone: 03122162647
• Email: meralbosnak[@]gazi.edu.tr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary immunodeficiencies (PID) are a heterogeneous group of diseases that occur as a result of disorders that affect the development, differentiation and/or function of various cells and building blocks in the immune system. Among the symptoms and complications of PID, pulmonary complications are very common and significantly increase the morbidity and mortality of the disease.

Description:

Among the symptoms and complications of PID, pulmonary complications are very common and significantly increase the morbidity and mortality of the disease. Recurrent respiratory infections are often the first warning sign in some types of PID and is a cause of mortality in adults with PID. Presence of 2 or more pneumonias per year is one of the 10 warning signs of PID. Respiratory system diseases are mainly caused by acute and chronic infections. Non-infectious respiratory system diseases and complications are asthma, bronchiectasis, bronchiolitis obliterans, interstitial lung disease, granulomatous lung disease and malignancies. These diseases significantly affect the quality of life of PID patients, limiting their ability to work and their physical and social activities. Health-related quality of life in PID patients is also significantly affected by delays in the diagnosis and treatment of infections. As survival from infections increases, non-infectious pulmonary complications are more common in PID patients. Permanent lung damage is seen at a rate of 20-40%, especially in PID patients with antibody deficiency. The main causes of exercise intolerance in patients with lung disease include isolated or associated factors such as increased symptoms (fatigue and shortness of breath in the lower extremities), development of dynamic hyperinflation, peripheral muscle dysfunction, abnormalities in oxygen transport and progressive loss of physical condition, physical inactivity. There are no studies evaluating exercise capacity, respiratory and peripheral muscle strength, inspiratory muscle endurance, and muscle oxygenation in children with PID. In studies conducted with post-infectious bronchiolitis obliterans patients, it has been shown that exercise capacity is reduced in these patients. There are no studies in the literature on pulmonary rehabilitation practices and efficacy in PID patients. The primary aim of this study: To investigate the effects of pulmonary rehabilitation on exercise capacity and muscle oxygenation in children with primary immunodeficiency. The secondary aim of this study: To investigate the effects of pulmonary rehabilitation on physical activity level, respiratory functions, peripheral and respiratory muscle strength, inspiratory muscle endurance, shortness of breath, fatigue and quality of life in children with primary immunodeficiency. Primary outcome measurement will be oxygen consumption (cardiopulmonary exercise test). Secondary outcome will be muscle oxygenation (Moxy device), physical activity level (multi sensor activity device), pulmonary function (spirometer), functional exercise capacity (six-minute walk test), respiratory (mouth pressure device) and peripheral muscle (hand-held dynamometer) strength, inspiratory muscle endurance (incremental threshold loading test), dyspnea (Modified Borg Scale (MBS)), fatigue (Modified Borg Scale) and quality of life (The Pediatric Quality of Life Inventory (PedsQL)).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 20, 2026
• Est. primary completion date: September 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria:

-Patients aged 6-18 years with primary immunodeficiency

Exclusion Criteria:

• Acute pulmonary exacerbation, acute upper or lower respiratory tract infection
• Serious neurological, neuromuscular, orthopedic and other systemic diseases or other diseases affecting physical functions
• Participating in a planned exercise program in the past three months
• Cognitive impairment, which may cause difficulty understanding and following exercise test instructions

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency
• Primary Immunodeficiency Diseases

Intervention

Other:
• Inspiratory muscle training
Inspiratory muscle training will be performed with Power Breathe®. Inspiratory muscle training will be given to the training group, starting from 50% of the MIP, and 2 sessions/day, 15 minutes/session. Patients will be asked to check breathing for 4-5 breaths after 8-10 consecutive breathing cycles. The patient will continue this cycle for 15 minutes.
• Upper extremity aerobic exercise training
Upper extremity aerobic exercise training will be performed 3 days/week, 1 session/day, 15 min/session using arm ergometer device accompanied by a physiotherapist. Aerobic exercise training workload will be 60-80% of maximal heart rate. In this study, the perception of dyspnea will be between 3-4, arm fatigue and general fatigue perception will be between 5-6, warm-up and cool-down periods will be 5 minutes, and pedaling speed will be 40-50 rev/min, according to MBS.
• Lower extremity aerobic exercise training
Lower extremity aerobic exercise training will be performed 3 days/week, 1 session/day, 15 minutes/session using the treadmill device, accompanied by a physiotherapist. Aerobic exercise training workload was set at 60-80% of maximal heart rate, dyspnea perception according to MBS was between 3-4, arm fatigue and general fatigue perception was between 5-6, and warm-up and cool-down periods were 5 minutes.
• Resistant exercise training
Upper and lower additional limb strengthening training will be performed 3 days/week, 1 session/day, 10 repetitions/sessions from the first day by using bullion weights in the presence of a physiotherapist. The upper extremity strengthening program will consist of a progressive exercise program to strengthen the shoulder flexors and abductors, and the lower extremity strengthening program to strengthen the knee extensors. The training workload will be increased progressively. For strength training, the workload will be adjusted so that the perception of fatigue is between 4 and 6 according to MBS.
• Thoracic expansion exercises
The control group will be asked to do thoracic expansion exercises seven days/week and 120 pieces/day for six weeks.

Locations

Country	Name	City	State
Turkey	Gazi University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Cardiopulmonary Rehabilitation Unit	Ankara	Çankaya

Sponsors (1)

Lead Sponsor	Collaborator
Gazi University

Country where clinical trial is conducted

Turkey, 

References & Publications (35)

Ameratunga R, Longhurst H, Lehnert K, Steele R, Edwards ESJ, Woon ST. Are All Primary Immunodeficiency Disorders Inborn Errors of Immunity? Front Immunol. 2021 Jul 21;12:706796. doi: 10.3389/fimmu.2021.706796. eCollection 2021. No abstract available. — View Citation

American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002 Aug 15;166(4):518-624. doi: 10.1164/rccm.166.4.518. No abstract available. — View Citation

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

ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. Erratum In: Am J Respir Crit Care Med. 2016 May 15;193(10):1185. — View Citation

Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, Rezaei N, Ochs HD, Aghamohammadi A. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol. 2017 Feb;13(2):101-115. doi: 10.1080/1744666X.2016.1224664. Epub 2016 Sep 16. — View Citation

Beenakker EA, van der Hoeven JH, Fock JM, Maurits NM. Reference values of maximum isometric muscle force obtained in 270 children aged 4-16 years by hand-held dynamometry. Neuromuscul Disord. 2001 Jul;11(5):441-6. doi: 10.1016/s0960-8966(01)00193-6. — View Citation

Clinical exercise testing with reference to lung diseases: indications, standardization and interpretation strategies. ERS Task Force on Standardization of Clinical Exercise Testing. European Respiratory Society. Eur Respir J. 1997 Nov;10(11):2662-89. doi: 10.1183/09031936.97.10112662. No abstract available. — View Citation

Crum EM, O'Connor WJ, Van Loo L, Valckx M, Stannard SR. Validity and reliability of the Moxy oxygen monitor during incremental cycling exercise. Eur J Sport Sci. 2017 Sep;17(8):1037-1043. doi: 10.1080/17461391.2017.1330899. Epub 2017 May 30. — View Citation

Domenech-Clar R, Lopez-Andreu JA, Compte-Torrero L, De Diego-Damia A, Macian-Gisbert V, Perpina-Tordera M, Roques-Serradilla JM. Maximal static respiratory pressures in children and adolescents. Pediatr Pulmonol. 2003 Feb;35(2):126-32. doi: 10.1002/ppul.10217. — View Citation

ERS Task Force; Palange P, Ward SA, Carlsen KH, Casaburi R, Gallagher CG, Gosselink R, O'Donnell DE, Puente-Maestu L, Schols AM, Singh S, Whipp BJ. Recommendations on the use of exercise testing in clinical practice. Eur Respir J. 2007 Jan;29(1):185-209. doi: 10.1183/09031936.00046906. — View Citation

Frohlich LF, Vieira PJ, Teixeira PJ, Silva FA, Ribeiro JP, Berton DC. Exercise capacity in adolescent and adult patients with post infectious bronchiolitis obliterans. Pediatr Pulmonol. 2014 Sep;49(9):911-8. doi: 10.1002/ppul.22929. Epub 2013 Dec 23. — View Citation

Gerbase MW, Soccal PM, Spiliopoulos A, Nicod LP, Rochat T. Long-term health-related quality of life and walking capacity of lung recipients with and without bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2008 Aug;27(8):898-904. doi: 10.1016/j.healun.2008.04.012. Epub 2008 Jun 10. — View Citation

Hampson FA, Chandra A, Screaton NJ, Condliffe A, Kumararatne DS, Exley AR, Babar JL. Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders. Clin Radiol. 2012 Jun;67(6):587-95. doi: 10.1016/j.crad.2011.10.028. Epub 2012 Jan 9. — View Citation

Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr. 2014 Jul 25;2:77. doi: 10.3389/fped.2014.00077. eCollection 2014. — View Citation

Kilic SS, Ozel M, Hafizoglu D, Karaca NE, Aksu G, Kutukculer N. The prevalences [correction] and patient characteristics of primary immunodeficiency diseases in Turkey--two centers study. J Clin Immunol. 2013 Jan;33(1):74-83. doi: 10.1007/s10875-012-9763-3. Epub 2012 Sep 15. — View Citation

Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dres M, Dube BP, Fauroux B, Gea J, Guenette JA, Hudson AL, Kabitz HJ, Laghi F, Langer D, Luo YM, Neder JA, O'Donnell D, Polkey MI, Rabinovich RA, Rossi A, Series F, Similowski T, Spengler CM, Vogiatzis I, Verges S. ERS statement on respiratory muscle testing at rest and during exercise. Eur Respir J. 2019 Jun 13;53(6):1801214. doi: 10.1183/13993003.01214-2018. Print 2019 Jun. — View Citation

Lee JA, Laurson KR. Validity of the SenseWear armband step count measure during controlled and free-living conditions. J Exerc Sci Fit. 2015 Jun;13(1):16-23. doi: 10.1016/j.jesf.2014.11.002. Epub 2015 Jan 29. — View Citation

Li AM, Yin J, Au JT, So HK, Tsang T, Wong E, Fok TF, Ng PC. Standard reference for the six-minute-walk test in healthy children aged 7 to 16 years. Am J Respir Crit Care Med. 2007 Jul 15;176(2):174-80. doi: 10.1164/rccm.200607-883OC. Epub 2007 Apr 26. — View Citation

Mahler DA, Rosiello RA, Harver A, Lentine T, McGovern JF, Daubenspeck JA. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis. 1987 Jun;135(6):1229-33. doi: 10.1164/arrd.1987.135.6.1229. — View Citation

Manson D, Reid B, Dalal I, Roifman CM. Clinical utility of high-resolution pulmonary computed tomography in children with antibody deficiency disorders. Pediatr Radiol. 1997 Oct;27(10):794-8. doi: 10.1007/s002470050235. — View Citation

Mattiello R, Sarria EE, Stein R, Fischer GB, Mocelin HT, Barreto SS, Lima JA, Brandenburg D. Functional capacity assessment in children and adolescents with post-infectious bronchiolitis obliterans. J Pediatr (Rio J). 2008 Jul-Aug;84(4):337-43. doi: 10.2223/JPED.1807. — View Citation

Modell V, Orange JS, Quinn J, Modell F. Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes. Immunol Res. 2018 Jun;66(3):367-380. doi: 10.1007/s12026-018-8996-5. — View Citation

Patel SA, Benzo RP, Slivka WA, Sciurba FC. Activity monitoring and energy expenditure in COPD patients: a validation study. COPD. 2007 Jun;4(2):107-12. doi: 10.1080/15412550701246658. — View Citation

Quinti I, Di Pietro C, Martini H, Pesce AM, Lombardi F, Baumghartner M, Colantuono S, Milito C, Tabolli S. Health related quality of life in common variable immunodeficiency. Yonsei Med J. 2012 May;53(3):603-10. doi: 10.3349/ymj.2012.53.3.603. — View Citation

Ridgers ND, Hnatiuk JA, Vincent GE, Timperio A, Barnett LM, Salmon J. How many days of monitoring are needed to reliably assess SenseWear Armband outcomes in primary school-aged children? J Sci Med Sport. 2016 Dec;19(12):999-1003. doi: 10.1016/j.jsams.2016.02.009. Epub 2016 Mar 3. — View Citation

Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery CF, Mahler DA, Make B, Rochester CL, Zuwallack R, Herrerias C. Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines. Chest. 2007 May;131(5 Suppl):4S-42S. doi: 10.1378/chest.06-2418. — View Citation

Routes J, Costa-Carvalho BT, Grimbacher B, Paris K, Ochs HD, Filipovich A, Hintermeyer M, de Melo KM, Workman S, Ito D, Ye X, Bonnet P, Li-McLeod J. Health-Related Quality of Life and Health Resource Utilization in Patients with Primary Immunodeficiency Disease Prior to and Following 12 Months of Immunoglobulin G Treatment. J Clin Immunol. 2016 Jul;36(5):450-61. doi: 10.1007/s10875-016-0279-0. Epub 2016 Apr 18. — View Citation

Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppanen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 Oct;42(7):1473-1507. doi: 10.1007/s10875-022-01289-3. Epub 2022 Jun 24. — View Citation

Uneri OS, Agaoglu B, Coskun A, Memik NC. Validity and reliability of Pediatric Quality of Life Inventory for 2- to 4-year-old and 5- to 7-year-old Turkish children. Qual Life Res. 2008 Mar;17(2):307-15. doi: 10.1007/s11136-007-9303-4. Epub 2008 Jan 18. — View Citation

Urschel S, Kayikci L, Wintergerst U, Notheis G, Jansson A, Belohradsky BH. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr. 2009 Jun;154(6):888-94. doi: 10.1016/j.jpeds.2008.12.020. Epub 2009 Feb 23. — View Citation

Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999 Feb;37(2):126-39. doi: 10.1097/00005650-199902000-00003. — View Citation

Verma N, Grimbacher B, Hurst JR. Lung disease in primary antibody deficiency. Lancet Respir Med. 2015 Aug;3(8):651-60. doi: 10.1016/S2213-2600(15)00202-7. Epub 2015 Jul 15. — View Citation

Wilson RC, Jones PW. A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise. Clin Sci (Lond). 1989 Mar;76(3):277-82. doi: 10.1042/cs0760277. — View Citation

Woszezenki CT, Heinzmann-Filho JP, Vendrusculo FM, Piva TC, Levices I, Donadio MV. Reference Values for Inspiratory Muscle Endurance in Healthy Children and Adolescents. PLoS One. 2017 Jan 25;12(1):e0170696. doi: 10.1371/journal.pone.0170696. eCollection 2017. — View Citation

Zenteno D, Puppo H, González R, Pavón D, Vera R, Torres R. Six minute walk test in children with post-infectious obliterans bronchiolitis. Its relation with spirometry. Rev Chil Enferm Respir. 2008;24:15-19. 24.

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxygen Consumption	Cardiopulmonary Exercises Test	First Day
Secondary	Pulmonary function (Forced vital capacity (FVC))	Pulmonary function will be evaluated with the spirometry. Dynamic lung volume measurements will be made according to American Thoracic Society (ATS) and European Respiratory Society (ERS) criteria. With the device, forced vital capacity (FVC) will be evaluated.	Second Day
Secondary	Pulmonary function (Forced expiratory volume in the first second (FEV1))	Pulmonary function will be evaluated with the spirometry. Dynamic lung volume measurements will be made according to ATS and ERS criteria. With the device, forced expiratory volume in the first second (FEV1) will be evaluated.	Second Day
Secondary	Pulmonary function (FEV1 / FVC)	Pulmonary function will be evaluated with the spirometry. Dynamic lung volume measurements will be made according to ATS and ERS criteria. With the device, FEV1 / FVC will be evaluated.	Second Day
Secondary	Pulmonary function (Flow rate 25-75% of forced expiratory volume (FEF 25-75%))	Pulmonary function will be evaluated with the spirometry. Dynamic lung volume measurements will be made according to ATS and ERS criteria. With the device, flow rate 25-75% of forced expiratory volume (FEF 25-75%) will be evaluated.	Second Day
Secondary	Pulmonary function (Peak flow rate (PEF))	Pulmonary function will be evaluated with the spirometry. Dynamic lung volume measurements will be made according to ATS and ERS criteria. With the device, peak flow rate (PEF) will be evaluated.	Second Day
Secondary	Respiratory Muscle Strength	Maximal inspiratory (MIP) and maximal expiratory (MEP) pressures expressing respiratory muscle strength were measured using a portable mouth pressure measuring device according to American Thoracic Society and European Respiratory Society criteria	Second Day
Secondary	Respiratory Muscle Endurance	Incremental threshold loading test	Second Day
Secondary	Peripheral Muscle Strength	Hand held dynamometer	Second Day
Secondary	Functional exercise capacity	6 minute walking test	Second Day
Secondary	Quality of Life (For Children)	The Pediatric Quality of Life Inventory (PedsQL): It includes 8 items that measure physical functionality, 5 items that measure emotional functionality, 5 items that measure social functionality, and 5 items that assess functionality at school. There are separate forms for parents and children. There are separate scales for children 5-7 years old, 8-12 years old and 13-18 years old. For parents, there are separate forms for 2-4 years, 5-7 years, 8-12 years and 13-18 years. Items are scored between 0-100. The higher the total PedsQL score, the better the health-related quality of life is perceived.	First Day
Secondary	Dyspnea	Modified Borg Scale: The Modified Borg scale is a subjective scale that scores 0-10 for breathlessness and fatigue at rest and/or during activity. The lowest 0 points "not at all" the highest 10 points "very severe" means shortness of breath.	First and Second Day
Secondary	Fatigue	Modified Borg Scale: The Modified Borg scale is a subjective scale that scores 0-10 for breathlessness and fatigue at rest and/or during activity. The lowest 0 points "not at all" the highest 10 points "very severe" means shortness of breath.	First and Second Day
Secondary	Muscle oxygenation	Moxy® monitor	First and Second Day
Secondary	Physical Activity Level (Total energy expenditure)	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Total energy expenditure (joule / day) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Active energy expenditure (joule / day))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Active energy expenditure (joule / day) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Physical activity time (min / day))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Physical activity time (min / day)will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Average metabolic equivalent (MET / day))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Average metabolic equivalent (MET / day) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Number of steps (steps / day))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Number of steps (steps / day) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Time spent lying down (min / day) days))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Time spent lying down (min / day) days) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day
Secondary	Physical activity (Sleep time (min / day))	Physical activity will be evaluated with the Multi sensor activity monitor (SenseWear®, Inc Pittsburgh, ABD). The patient will wear the multisensor physical activity monitor over the triceps muscle of the non-dominant arm for 4 continuous days. The patient will be informed about removing the device while taking a bath. Sleep time (min / day) will be measured with the multi-sensor physical activity monitor. The parameters measured over two days will be averaged and analyzed with the "SenseWear® 7.0 Software" program.	Second Day