Clinical trial NCT03448627: Physical Impairments in Allogeneic-HSCT
Official title: Physiological Responses to Maximal Exercise Capacity and Muscle Strength in Survived Hematopoietic Stem Cell Transplantation Recipients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stem Cell Transplantation
Keywords: stem cell transplantation
Pulmonary Functions
muscle strength
exercise capacity
Lead sponsor: Gazi University
Sponsor class: OTHER
First posted: 2018-02-28
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 66 recipients underwent allogeneic HSCT who were at minimum 100 days status post-transplantation compared with 50 healthy individuals.

All recipients transplanted at the Bone Marrow Transplantation Unit of University Faculty of Medicine. All measurements were done by a physiotherapist at Cardiopulmonary Unit of University Faculty of Health Science Department of Physiotherapy and Rehabilitation. Demographic and clinical characteristics of all participants were recorded. Study was planned as retrospective, cross sectional and approved by the local Ethics Committee. Informed consent was obtained from all individual participants included in the study.

Brief summary: Pulmonary functions, exercise capacity and muscle strength deteriorate in survived hematopoietic stem cell transplantation (HSCT) recipients due to toxic effects of chemotherapy, radiotherapy, conditioning regimens and/or corticosteroid use before HSCT, prolonged stay of recipients in rooms with laminar airflow and strict infection control rules during process of HSCT. There are also limited numbers of studies demonstrated pulmonary function abnormalities, decreased maximal exercise capacity, respiratory and peripheral muscle weakness in recipients. Current study was planned since no study compared pulmonary functions, maximal exercise capacity, respiratory and peripheral muscle strength between recipients and healthy individuals in the literature.

Detailed description: Treatments of hematologic malignancies consist of chemotherapy, radiotherapy, surgery, medical treatment, supportive care and/or hematopoietic stem cell transplantation (HSCT) which is resulted in early or late adverse effects on body systems, tissues and organs. Physical deconditioning is also observed in patients with hematologic malignancies because of reasons such as neurotoxic and pulmonary toxic effects of long term these anticancer treatments, immobilization, recommendation of resting and avoiding intense exercise, nutrition problems, severe anemia and thrombocytopenia etc. For these reasons, normal physical activities may not be kept on by patients which induces decreased physical performance.

The HSCT provides longer survival with standard treatments for patients with hematological malignancies while it increases risk of HSCT-related toxicity, complications and even mortality. Infectious and non-infectious pulmonary complications occur in about 60% of HSCT recipients and intensive-care unit support is also required in one-third of recipients for these reasons. Restrictive lung disease prior to allogeneic HSCT is related to early respiratory failure, non-relapse mortality and respiratory muscle weakness in post transplantation period. Therefore pulmonary restriction is considered as a risk factor for complications or failure of HSCT. Moreover it is known that carbon monoxide diffusing capacity of lungs which is the most common abnormality seen in pulmonary function test, respiratory muscle strength and functional exercise capacity are reduced in the majority of patients before HSCT. In addition to muscle weakness and decreased exercise capacity at prior to HSCT, patients experience more reduction in both inspiratory and expiratory muscles and exercise capacity after HSCT. Unfortunately, exercise capacity and peripheral muscle strength are decreased in HSCT recipients in spite of doing regular and planned exercise during acute process of HSCT. The average reduction in functional exercise capacity of recipients is 48 m. As shown in the literature, limited number of study has used evaluation of maximal exercise capacity with Modified-Incremental Shuttle Walk Test (ISWT) in HSCT patients and recipients. On the other hand, it has been reported that ISWT is a reliable test and has no adverse event or side effects for HSCT recipients in these studies, as well. Despite the fact that there is no negative feedback related to using of this test in recipients, no study comprehensively demonstrated influence of HSCT on maximal exercise capacity.

Impairments in pulmonary functions, respiratory muscle strength and maximal exercise capacity have been demonstrated in limited number of studies. Moreover, there is no study compared pulmonary functions, respiratory muscle strength and maximal exercise capacity between HSCT recipients and healthy individuals. Therefore investigators aimed to compare aforementioned outcomes between recipients and healthy individuals.

Eligibility criteria: Inclusion Criteria for recipients:

* between ages of 18 and 70
* under standard medical treatment
* underwent allogeneic HSCT who were at minimum 100 days status post-transplantation

Exclusion Criteria for recipients:

* having cognitive disorder, orthopedic or neurological disease with a potential to affect assessment of maximal exercise capacity,
* having comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), acute respiratory or other infections,
* having problems like visual and mucositis which may prevent measurements,
* acute hemorrhage anywhere in the body,
* hemoglobin value less than 8 g/L and platelet count less than 10.000 mm3

Inclusion Criteria for healthy individuals:

* being individuals without known and diagnosed any chronic diseases
* not actively smoking
* their cigarette exposure is not greater than 5 pack\*year.

Primary outcomes:
measure: Modified-Incremental Shuttle Walk Test (ISWT)
timeFrame: 15-20 minutes
Secondary outcomes:
measure: pulmonary function test
timeFrame: 5 minutes
measure: inspiratory and expiratory muscle strength (MIP, MEP)
timeFrame: 5-10 minutes
measure: Quadriceps femoris muscle strength
timeFrame: 5 minutes
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Gazi University Faculty of Health Science Department of PhysioTherapy
Study officials:
affiliation: Gazi University
name: Gülşah Barğı, PhD
role: STUDY_CHAIR
affiliation: Gazi University
name: Meral Boşnak Güçlü, PhD
role: STUDY_DIRECTOR
affiliation: Bahçeşehir University
name: Gülsan Türköz Sucak
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kovalszki A, Schumaker GL, Klein A, Terrin N, White AC. Reduced respiratory and skeletal muscle strength in survivors of sibling or unrelated donor hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008 Jun;41(11):965-9. doi: 10.1038/bmt.2008.15. Epub 2008 Feb 11.
citation: Morishita S, Kaida K, Yamauchi S, Sota K, Ishii S, Ikegame K, Kodama N, Ogawa H, Domen K. Relationship between corticosteroid dose and declines in physical function among allogeneic hematopoietic stem cell transplantation patients. Support Care Cancer. 2013 Aug;21(8):2161-9. doi: 10.1007/s00520-013-1778-7. Epub 2013 Mar 9.
citation: Knols RH, de Bruin ED, Uebelhart D, Aufdemkampe G, Schanz U, Stenner-Liewen F, Hitz F, Taverna C, Aaronson NK. Effects of an outpatient physical exercise program on hematopoietic stem-cell transplantation recipients: a randomized clinical trial. Bone Marrow Transplant. 2011 Sep;46(9):1245-55. doi: 10.1038/bmt.2010.288. Epub 2010 Dec 6.
citation: Shelton ML, Lee JQ, Morris GS, Massey PR, Kendall DG, Munsell MF, Anderson KO, Simmonds MJ, Giralt SA. A randomized control trial of a supervised versus a self-directed exercise program for allogeneic stem cell transplant patients. Psychooncology. 2009 Apr;18(4):353-9. doi: 10.1002/pon.1505.
citation: Morishita S, Kaida K, Yamauchi S, Wakasugi T, Ikegame K, Ogawa H, Domen K. Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation. Eur J Cancer Care (Engl). 2017 Jul;26(4). doi: 10.1111/ecc.12669. Epub 2017 Feb 21.
citation: Bargi G, Guclu MB, Aribas Z, Aki SZ, Sucak GT. Inspiratory muscle training in allogeneic hematopoietic stem cell transplantation recipients: a randomized controlled trial. Support Care Cancer. 2016 Feb;24(2):647-659. doi: 10.1007/s00520-015-2825-3. Epub 2015 Jul 2.
citation: Bird L, Arthur A, Niblock T, Stone R, Watson L, Cox K. Rehabilitation programme after stem cell transplantation: randomized controlled trial. J Adv Nurs. 2010 Mar;66(3):607-15. doi: 10.1111/j.1365-2648.2009.05232.x.