Hematopoietic Stem Cell Transplantation (HSCT)NCT07061444
Effects of Different Inspiratory Muscle Training Protocols in Hematopoietic Stem Cell Transplant Recipients
A study testing Inspiratory Muscle Training and Functional Inspiratory Muscle Training in people with Hematopoietic Stem Cell Transplantation (HSCT) and Pulmonary Rehabilitation, run by Ceren Derya Gültekin at 1 site in Turkey (Türkiye).
Trial summary
Introduction: After haematopoietic stem cell transplantation (HSCT), patients often experience complications such as respiratory difficulties, fatigue and decreased quality of life. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation (HSCT), Pulmonary Rehabilitation, Inspiratory Muscle Training
- What is being tested?
- Inspiratory Muscle Training and Functional Inspiratory Muscle Training
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 2 Aug 2025to 2 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Planned haematopoietic stem cell transplantation in the adult bone marrow transplant unit
- Between the ages of 18-65
- Under standard medical treatment, including immunosuppressives, antibiotics and other medications
- Ability to walk, co-operate and be clinically stable
- No history of orthopaedic, neurological, cardiac disorders
Who cannot join
- Cognitive disorders
- Have orthopaedic or neurological diseases that may affect the assessment of physical fitness tests
- Having comorbidities such as asthma, COPD
- Conditions in which exercise training is contraindicated, such as acute bleeding, haemoglobin value <5 g/dl, platelet count ≤10000 mm3, high fever (body temperature >38◦C), severe pain, confusion, dizziness, nausea and vomiting
- Patients with pneumonia or any acute infection
- -≥ 3 consecutive sessions of interruption of the exercise group subjects' attendance to the training protocol
- Loss of willingness to participate in the research during the research process
- Development of clinical haemodynamic instability in patients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Istinye University
Istanbul, Zeytinburnu, 34010
Ceren D Gültekin, +905383200141, cerenderya1@gmail.com
About this study
Introduction: After haematopoietic stem cell transplantation (HSCT), patients often experience complications such as respiratory difficulties, fatigue and decreased quality of life.
The aim of the study was to compare the effectiveness of different inspiratory muscle training (IMT) protocols on respiratory muscle strength and endurance, dyspnoea, maximal exercise capacity, diaphragmatic function, respiratory function parameters, peripheral muscle strength, fatigue, quality of life, oxidative stress parameters, muscle biomarkers and inflammatory biomarkers in HSCT recipients during the transplantation process.
Read more
Method: The study will include patients between 18-65 years of age, who are able to walk and understand the instructions, who do not have orthopedic, neurological or cardiac disorders and who will undergo haematopoietic stem cell transplantation. Patients with cognitive impairments; orthopedic or neurological diseases that may affect the evaluation of physical fitness tests; patients with comorbidities such as asthma, COPD will not be included in the study. In cases where the exercise group subjects' attendance to the training protocol is interrupted for 3 sessions or more consecutively, the voluntariness to participate in the research is lost during the research process, and clinical haemodynamic instability develops in the subjects, the participant will be excluded from the study. Patients in whom exercise training is contraindicated such as acute bleeding, haemoglobin value <5 g/dl, platelet count ≤10000 mm3, high fever (body temperature >38◦C), severe pain, confusion, dizziness, nausea and vomiting will not be included in the exercise.
It is planned as a prospective, randomised controlled and single blinded study. Triple blinding could not be performed due to the executive's evaluation and implementation of the study protocol. Patients included in the study will be randomly divided into 3 study groups of 15 people each. Stratified randomisation technique will be used. A total of 45 haematopoietic stem cell transplant patients will be included in the study. Patients will be evaluated 3 times: before exercise therapy (pre-HSCT), before and after starting the preparatory regime and after exercise therapy (post-HSCT). Primary assessment measures are dyspnoea, maximal exercise capacity, respiratory muscle strength and endurance, diaphragmatic respiration, oxidative stress parameters, inflammatory markers, muscle biomarkers, pulmonary function test. Secondary assessment measures were peripheral muscle strength, fatigue, depression, and quality of life.
The research arms consisted of a total of 45(15;15;15) people in 3 groups: 'standard inspiratory muscle training group', 'functional respiratory muscle training group' and 'control group' with 15 people in each group. All patients in the control and research groups will receive inspiratory muscle training for a total of 30 minutes twice a day, every weekday during the transplantation period, starting at the end of the session in which their initial assessment was made. Functional respiratory muscle training group will perform functional exercises simultaneously with inspiratory muscle training 3 days a week (Monday-Wednesday-Friday or Tuesday-Thursday-Saturday). All exercises will be supervised by a physiotherapist.
The most important originality of this study is that it is the first study to investigate the effects of functional respiratory muscle training on respiratory parameters, diaphragm function, peripheral muscle strength, maximum oxygen consumption, dyspnoea, fatigue, depression and quality of life in HSCT recipients. It is the first randomised controlled study to demonstrate the effect of inspiratory muscle training on diaphragmatic function in HSCT recipients and it is one of the rare studies in which exercise capacity will be evaluated by cardiopulmonary exercise test. It is also the first study to examine the relationship between inspiratory muscle training and muscle biomarkers and oxidative stress parameters in HSCT recipients.
H0: There is no difference in the effectiveness of different inspiratory muscle training protocols on maximal exercise capacity, respiratory muscle strength, respiratory muscle endurance, diaphragmatic function, oxidative stress parameters, muscle biomarkers, inflammatory biomarkers, dyspnoea, peripheral muscle strength, quality of life, fatigue, depression in haematopoietic stem cell transplant recipients.
H1: There is a difference in the effectiveness of different inspiratory muscle training protocols on maximal exercise capacity, respiratory muscle strength, respiratory muscle endurance, diaphragmatic function, oxidative stress parameters, muscle biomarkers, inflammatory biomarkers, dyspnoea, peripheral muscle strength, quality of life, fatigue, depression in haematopoietic stem cell transplant recipients.
- Conditions
- Hematopoietic Stem Cell Transplantation (HSCT), Pulmonary Rehabilitation, Inspiratory Muscle Training
- Being tested
- Inspiratory Muscle Training, Functional Inspiratory Muscle Training, Sham Inspiratory Muscle Training
- Keywords
- inspiratory muscle training, pulmonary rehabilitation, hematopoietic stem cell transplantation, respiratory therapy, respiratory muscle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inspiratory Muscle TrainingOther
Inspiratory muscle training will be performed at 40% of MIP workload, 1 set of 8-10 diaphragmatic respirations for 15 minutes, with 5-10 seconds rest intervals between sets. 5 days a week, 2 sessions per day.
Functional Inspiratory Muscle TrainingOther
This study investigates the integration of functional inspiratory muscle training (IMT) with conventional physiotherapy. Patients will perform inspiratory muscle training using the threshold loading technique with the POWERbreathe IMT device, combined with functional exercises. The functional IMT protocol will be administered face-to-face, 3 days a week, for 30 minutes per session over a 6-week period. Resistance on the IMT device will be set to 40% of the patient's maximal inspiratory pressure (MIP) and adjusted weekly based on measured MIP values. Exercises will be categorized into three progressive difficulty levels (easy, medium, and hard), with each stage lasting 2 weeks. Patients will inhale through the POWERbreathe IMT device during exercise movements and exhale during the return phase, ensuring simultaneous respiratory muscle activation and functional training.
Sham Inspiratory Muscle TrainingOther
Control group will be performed at 10% of the MIP workload, 1 set of 8-10 diaphragmatic breaths for 15 minutes, with 5-10 seconds rest intervals between sets. 2 sessions per day, 5 days a week.
| Study group | Role | What they receive |
|---|---|---|
| 1. Inspiratory Muscle Training Group | Active comparator | Fifteen patients meeting the inclusion criteria will undergo standard inspiratory muscle training using the PowerBreathe Classic device (HaB International Ltd., Southam, UK). IMT will be performed at 40% of the maximum inspiratory pressure (MIP), with weekly re-assessment of MIP by the responsible researcher to adjust the training workload. Each session will consist of 8-10 diaphragmatic breaths, followed by a rest interval of 5-10 seconds, lasting 15 minutes per session. Training will be conducted twice daily, five days per week.
Vital signs, including heart rate and oxygen saturation, will be monitored continuously throughout the exercises, and measurements will also be taken before, after, and during the first minute of recovery. This progressive IMT protocol aims to optimize inspiratory muscle strength through evidence-based threshold pressure loading, ensuring patient safety and effective respiratory muscle adaptation over time. Receives: Other: Inspiratory Muscle Training |
| 2. Functional Inspiratory Muscle Training Group | Active comparator | Fifteen patients will undergo functional respiratory muscle training integrating inspiratory muscle training (IMT) and functional exercises. The POWERbreathe IMT device, using a threshold loading technique, will be set at 40% of maximum inspiratory pressure (MIP) and adjusted weekly based on updated MIP values. Training sessions will be conducted face-to-face, three times per week, for 30 minutes under physiotherapist supervision, while classical IMT will continue on other days. During each session, heart rate, oxygen saturation, fatigue, and dyspnoea perception will be monitored before, during, and after exercises, including the first minute of recovery. The six-week program will involve progressive functional exercises classified into three difficulty levels-easy, medium, and hard-spanning two-week intervals. Patients will be instructed to inhale through the POWERbreathe device during movement and exhale upon returning to the starting position. Receives: Other: Functional Inspiratory Muscle Training |
| 3. Control Group | Placebo comparator | Sham protocol will be applied to 15 randomly selected patients. All vital signs of the patient will be taken before and after exercise training and during the 1st minute recovery period. Oxygen saturation monitoring and heart rate will be measured throughout the exercise. Type: threshold loading inspiratory muscle training (PowerBreath classic will be used.) Progression: will be studied at 10% of the re-measured MIP at the beginning of each week. Receives: Other: Sham Inspiratory Muscle Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dyspnea Perception Measurement
Dyspnea perception will be assessed using the Modified Borg Scale and the Modified Medical Research Council (MMRC) Dyspnea Scale.
Modified Borg Scale: A subjective scale to assess dyspnea at rest and/or during activity. The scale ranges from 0-10, where 0 indicates no dyspnea and 10 indicates very severe dyspnea, reflecting the participant's perceived breathlessness.
Modified MMRC Dyspnea Scale: This scale evaluates dyspnea during daily activities. It is graded as follows:
0: No dyspnea except for severe activity.
- Dyspnea during fast walking or uphill climbing.
- Dyspnea causes slower movement or stops on flat ground.
- Dyspnea causes stopping after walking 100 meters or a few minutes.
- Dyspnea occurs during dressing or undressing, preventing leaving the house.
Unit of Measure:
Modified Borg Scale: 0-10 points
MMRC Dyspnea Scale: Grade 0-4
Measured: "Through study completion, an average of 1 year"
Cardiopulmonary Function Measurement
Cardiopulmonary function will be assessed using the Cardiopulmonary Exercise Test (CPET) with the MES VO₂max Finder device (Poland), providing measurements of VO₂, VCO₂, VE, RER, and ventilatory threshold following ATS and ERS standards.
Protocol:
Pre-test Preparation: Avoid caffeine and vigorous exercise for 24 hours prior.
Test Protocol: The Modified Bruce protocol with progressive increases in speed (2.7 to 8.8 km/h) and incline (0 to 20%) every 3 minutes.
Vital Signs Monitoring: Heart rate, blood pressure, SpO₂, dyspnea, and fatigue monitored.
Test Duration: 8-12 minutes, ending when two criteria are met (exhaustion, 90% max heart rate, RER ≥ 1.10, or blood lactate > 8.0 mmol/L).
Cooldown: 3-minute cooldown post-test.
Gas exchange analyzed breath-by-breath, with calibration per ATS/ERS guidelines.
Unit of Measure:
VO₂: mL/min VCO₂: mL/min VE: L/min RER: Ratio Ventilatory Threshold: L/min
Measured: "Through study completion, an average of 1 year"
Respiratory Muscle Strength Measurement
Respiratory muscle strength will be assessed by measuring Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP) using the Micro Medical Micro RPM device (Rochester, UK), with measurements recorded in cmH₂O.
MIP: Measured during maximal inspiration against a closed airway after full expiration.
MEP: Measured during maximal expiration against a closed airway after full inspiration.
Both MIP and MEP will be maintained for 1-3 seconds. Three measurements will be taken, and the best value will be recorded. Results will be expressed as a percentage of normal reference values adjusted for age and gender.
Disposable, personalized mouthpieces and filters will be used to prevent infection, following ERS (2019) guidelines.
Unit of Measure:
MIP and MEP: cmH₂O, expressed as a percentage of normal reference values.
Measured: "Through study completion, an average of 1 year"
Respiratory Muscle Endurance Measurement
Respiratory muscle endurance will be assessed using the Powerbreath Plus MR (HaB International Ltd., Southam, England), an inspiratory muscle training device employing a constant threshold load technique. The resistance of the device will be set at 60% of the participant's Maximum Inspiratory Pressure (MIP) value.
During the test:
The device will be placed in the participant's mouth, and the nose will be closed with a clip.
The participant will be instructed to breathe through the device for a maximum of 10 minutes.
Participants will be informed before the test that they can remove the device and stop the test if they feel excessive shortness of breath or discomfort.
The time the participant is able to continue the test will be recorded in seconds.
Unit of Measure:
The unit of measure for this outcome is seconds for the duration the participant can continue the test.
Measured: "Through study completion, an average of 1 year"
Diaphragm Function and Thickness Measurement
Diaphragm function and thickness will be assessed using Aplio XG ultrasonography (Toshiba, Japan) with patients in a supine position.
Diaphragm Thickness: Measured using B-mode ultrasound with a 7 MHz transducer at the 9th intercostal space on the anterior axillary line at the end of expiration. Left hemidiaphragm imaging will not be performed due to anatomical limitations.
Diaphragm Movement: Analyzed using M-mode ultrasonography with a 3.5 MHz transducer in a longitudinal semi-coronal plane. Excursion during calm breathing, deep breathing, and sniff test excursion will be assessed. The difference in diaphragm movement between inspiration and expiration will be calculated across three respiratory cycles.
Unit of Measure:
Diaphragm thickness and excursion will be expressed in millimeters (mm).
Measured: "Through study completion, an average of 1 year"
Inflammatory Markers Measurement
Blood samples will be collected in blood collection tubes and centrifuged at 3,000 x g for 10 minutes to obtain the serum supernatant. The serum samples will be stored at -80°C until the day of the experiment.
The following inflammatory markers will be measured:
Proinflammatory markers: TNF-α and IL-6
Anti-inflammatory markers: IL-2 and IL-10
These markers will be measured using commercially available ELISA-based kits (Mybiosource Co., USA).
Unit of Measure:
The unit of measure will be expressed in pg/mL or ng/mL, depending on the kit's specifications for each marker.
Measured: "Through study completion, an average of 1 year"
Oxidative Stress Parameters Measurement
Blood samples will be collected in blood collection tubes, centrifuged at 3,000 x g for 10 minutes to obtain serum supernatant, and stored at -80°C until analysis.
Total Antioxidant Status (TAS): Measured by spectrophotometry (Thermo Scientific, Varioskan LUX, USA) using a commercial kit (Rel Assay Diagnostics, Turkey). Antioxidants reduce the ABTS radical to its colorless form, with absorbance at 660 nm correlating to TAS.
Total Oxidant Status (TOS): Measured using a commercial kit (Rel Assay Diagnostics, Turkey) and spectrophotometrically (Thermo Scientific, Varioskan LUX, USA).
Unit of Measure:
TAS: mmol Trolox Equiv/L
TOS: µmol H₂O₂ Equiv/L (or as per the kit specifications)
Measured: "Through study completion, an average of 1 year"
Muscle Biomarkers Measurement
Serum CK-MM and CK-MB concentrations will be measured using ELISA-based commercial kits. Microwells pre-coated with monoclonal antibodies will capture the biomarkers, followed by detection using a biotin-conjugated antibody. After washing, HRP-conjugated avidin will be added, and TMB substrate will be used for colorimetric detection. Absorbance will be measured at 450 nm using a spectrophotometric plate reader (Thermo Scientific, USA).
Blood samples (15 mL × 3 tubes) will be collected twice, before and after treatment, in gel biochemistry tubes at İstinye University laboratories. Serum will be obtained by centrifugation and stored at -80°C until analysis. In addition, CRP, hemoglobin, platelet, and albumin levels will be recorded from patient follow-up files.
Unit of Measure:
CK-MM and CK-MB concentrations: ng/mL (as per the ELISA kit specifications)
Measured: "Through study completion, an average of 1 year"
Pulmonary Function Test
The pulmonary function test will be performed using a spirometer (Cosmed Pony FX, Italy) following ATS/ERS guidelines. The test will measure:
Forced Vital Capacity (FVC)
Forced Expiratory Volume in the First Second (FEV1)
FEV1/FVC ratio
Peak Expiratory Flow (PEF)
Forced Expiratory Midflow Rate (FEF25-75%)
The test will be conducted in a sitting position, with the best of three technically acceptable maneuvers demonstrating 95% agreement selected for analysis. Parameters will be expressed as a percentage of predicted values adjusted for age, height, and gender. Sterilization procedures, disposable, and personalized mouthpieces/filters will be used to prevent infection.
Unit of Measure:
FVC, FEV1, FEV1/FVC, PEF, FEF25-75%: Percentage of predicted values (adjusted for age, height, and gender)
Measured: "Through study completion, an average of 1 year"
Secondary outcomes (4)
Peripheral Muscle Strength Measurement
Peripheral muscle strength will be assessed using a portable manual muscle strength measuring device (Model 01165, Lafayette, IN, USA) and a Jamar Hydraulic Hand Dynamometer (Jamar, Nottinghamshire, UK). The muscles assessed include:
Upper extremity: Shoulder abductor, shoulder flexor, elbow flexor, and elbow extensor.
Lower extremity: Hip flexor and knee extensor.
Grip strength will be measured in a sitting position with the elbow flexed at 90° and wrist neutral. Three measurements will be taken for each side (right and left), and the best value recorded in kilograms (kg) for grip strength and Newton-meters (Nm) for knee extensor strength. The measurements will be interpreted using reference equations from Andrews et al.
Unit of Measure:
Grip strength: kg Knee extensor strength: Nm
Minimal Clinical Significance:
Knee extensor strength: 17.2 Nm
Grip strength: 6.25 kg
Measured: "Through study completion, an average of 1 year"
Fatigue Perception Measurement
Fatigue perception will be assessed using the Turkish adaptation of the Fatigue Severity Scale (FSS). The self-administered scale consists of nine items that evaluate the severity of fatigue experienced by the participant. Each item is rated on a 7-point scale, where 1 indicates "strongly disagree" and 7 indicates "strongly agree."
The total score can range from a minimum of 9 to a maximum of 63. A total score of 36 or above indicates severe fatigue according to the criteria established by Armutlu et al. (2007).
The scale provides a reliable assessment of the participant's perceived fatigue severity, allowing for the evaluation of changes over time.
Measured: "Through study completion, an average of 1 year"
Depression Measurement
Depression will be assessed using the 21-item self-administered Beck Depression Inventory (BDI), developed by Beck et al. The scale consists of 21 items that assess depression-specific conditions. Each item is scored on a 4-point scale, where scores range from 0 to 3. A higher score indicates a higher level of depression.
The total score on the inventory can range from 0 (no depression) to 63 (severe depression). A score above 17 is accepted as indicative of the presence of depression.
The unit of measure for this outcome is the total score, reported in points.
Measured: "Through study completion, an average of 1 year"
Quality of Life Measurement
Quality of life will be assessed using the Turkish adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, Version 3.0). The Turkish version has been proven to be reliable and valid for use with patients. The questionnaire consists of 30 items, designed to evaluate the quality of life of cancer patients. It comprises nine subscales, which include:
Five functional scales: Physical, role, cognitive, emotional, and social functioning.
One global health and quality of life scale.
Three symptom scales: Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, loss of appetite, constipation, diarrhoea, and financial difficulties.
Additionally, the questionnaire includes items assessing the financial impact of the disease and its treatment.
The unit of measure for this outcome is the total score, reported in points, derived from responses to the individual items within the subscales.
Measured: "Through study completion, an average of 1 year"
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2025
- Study start2 Aug 2025 (estimated)
- Primary completion2 Aug 2026 (estimated)
- Study completion2 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Stem Cell Transplantation (HSCT)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ceren Derya Gültekin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ceren Derya Gültekin, Istinye University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07061444
- Sponsor's protocol ID
- 24-207
- Status last verified
- Jul 2025
- First submitted
- 31 Dec 2024
- Last updated
- 11 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plans to share individual participant data.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Different Inspiratory Muscle Training Protocols in Hematopoietic Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT07061444
- Acronym / sponsor ID
- 24-207
- Conditions
- Hematopoietic Stem Cell Transplantation (HSCT), Pulmonary Rehabilitation, Inspiratory Muscle Training
- Keywords
- inspiratory muscle training, pulmonary rehabilitation, hematopoietic stem cell transplantation, respiratory therapy, respiratory muscle
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Ceren Derya GültekinUniversity, hospital or other
- Study start
- 2 Aug 2025 (estimated)
- Primary completion
- 2 Aug 2026 (estimated)
- Study completion
- 2 Sep 2026 (estimated)
- First posted
- 11 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: After haematopoietic stem cell transplantation (HSCT), patients often experience complications such as respiratory difficulties, fatigue and decreased quality of life.
The aim of the study was to compare the effectiveness of different inspiratory muscle training (IMT) protocols on respiratory muscle strength and endurance, dyspnoea, maximal exercise capacity, diaphragmatic function, respiratory function parameters, peripheral muscle strength, fatigue, quality of life, oxidative stress parameters, muscle biomarkers and inflammatory biomarkers in HSCT recipients during the transplantation process.
Method: The study will include patients between 18-65 years of age, who are able to walk and understand the instructions, who do not have orthopedic, neurological or cardiac disorders and who will undergo haematopoietic stem cell transplantation. Patients with cognitive impairments; orthopedic or neurological diseases that may affect the evaluation of physical fitness tests; patients with comorbidities such as asthma, COPD will not be included in the study. In cases where the exercise group subjects' attendance to the training protocol is interrupted for 3 sessions or more consecutively, the voluntariness to participate in the research is lost during the research process, and clinical haemodynamic instability develops in the subjects, the participant will be excluded from the study. Patients in whom exercise training is contraindicated such as acute bleeding, haemoglobin value <5 g/dl, platelet count ≤10000 mm3, high fever (body temperature >38◦C), severe pain, confusion, dizziness, nausea and vomiting will not be included in the exercise.
It is planned as a prospective, randomised controlled and single blinded study. Triple blinding could not be performed due to the executive's evaluation and implementation of the study protocol. Patients included in the study will be randomly divided into 3 study groups of 15 people each. Stratified randomisation technique will be used. A total of 45 haematopoietic stem cell transplant patients will be included in the study. Patients will be evaluated 3 times: before exercise therapy (pre-HSCT), before and after starting the preparatory regime and after exercise therapy (post-HSCT). Primary assessment measures are dyspnoea, maximal exercise capacity, respiratory muscle strength and endurance, diaphragmatic respiration, oxidative stress parameters, inflammatory markers, muscle biomarkers, pulmonary function test. Secondary assessment measures were peripheral muscle strength, fatigue, depression, and quality of life.
The research arms consisted of a total of 45(15;15;15) people in 3 groups: 'standard inspiratory muscle training group', 'functional respiratory muscle training group' and 'control group' with 15 people in each group. All patients in the control and research groups will receive inspiratory muscle training for a total of 30 minutes twice a day, every weekday during the transplantation period, starting at the end of the session in which their initial assessment was made. Functional respiratory muscle training group will perform functional exercises simultaneously with inspiratory muscle training 3 days a week (Monday-Wednesday-Friday or Tuesday-Thursday-Saturday). All exercises will be supervised by a physiotherapist.
The most important originality of this study is that it is the first study to investigate the effects of functional respiratory muscle training on respiratory parameters, diaphragm function, peripheral muscle strength, maximum oxygen consumption, dyspnoea, fatigue, depression and quality of life in HSCT recipients. It is the first randomised controlled study to demonstrate the effect of inspiratory muscle training on diaphragmatic function in HSCT recipients and it is one of the rare studies in which exercise capacity will be evaluated by cardiopulmonary exercise test. It is also the first study to examine the relationship between inspiratory muscle training and muscle biomarkers and oxidative stress parameters in HSCT recipients.
H0: There is no difference in the effectiveness of different inspiratory muscle training protocols on maximal exercise capacity, respiratory muscle strength, respiratory muscle endurance, diaphragmatic function, oxidative stress parameters, muscle biomarkers, inflammatory biomarkers, dyspnoea, peripheral muscle strength, quality of life, fatigue, depression in haematopoietic stem cell transplant recipients.
H1: There is a difference in the effectiveness of different inspiratory muscle training protocols on maximal exercise capacity, respiratory muscle strength, respiratory muscle endurance, diaphragmatic function, oxidative stress parameters, muscle biomarkers, inflammatory biomarkers, dyspnoea, peripheral muscle strength, quality of life, fatigue, depression in haematopoietic stem cell transplant recipients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1. Inspiratory Muscle Training Group | Active comparator | Other: Inspiratory Muscle TrainingFifteen patients meeting the inclusion criteria will undergo standard inspiratory muscle training using the PowerBreathe Classic device (HaB International Ltd., Southam, UK). IMT will be performed at 40% of the maximum inspiratory pressure (MIP), with weekly re-assessment of MIP by the responsible researcher to adjust the training workload. Each session will consist of 8-10 diaphragmatic breaths, followed by a rest interval of 5-10 seconds, lasting 15 minutes per session. Training will be conducted twice daily, five days per week. Vital signs, including heart rate and oxygen saturation, will be monitored continuously throughout the exercises, and measurements will also be taken before, after, and during the first minute of recovery. This progressive IMT protocol aims to optimize inspiratory muscle strength through evidence-based threshold pressure loading, ensuring patient safety and effective respiratory muscle adaptation over time. |
| 2. Functional Inspiratory Muscle Training Group | Active comparator | Other: Functional Inspiratory Muscle TrainingFifteen patients will undergo functional respiratory muscle training integrating inspiratory muscle training (IMT) and functional exercises. The POWERbreathe IMT device, using a threshold loading technique, will be set at 40% of maximum inspiratory pressure (MIP) and adjusted weekly based on updated MIP values. Training sessions will be conducted face-to-face, three times per week, for 30 minutes under physiotherapist supervision, while classical IMT will continue on other days. During each session, heart rate, oxygen saturation, fatigue, and dyspnoea perception will be monitored before, during, and after exercises, including the first minute of recovery. The six-week program will involve progressive functional exercises classified into three difficulty levels-easy, medium, and hard-spanning two-week intervals. Patients will be instructed to inhale through the POWERbreathe device during movement and exhale upon returning to the starting position. |
| 3. Control Group | Placebo comparator | Other: Sham Inspiratory Muscle TrainingSham protocol will be applied to 15 randomly selected patients. All vital signs of the patient will be taken before and after exercise training and during the 1st minute recovery period. Oxygen saturation monitoring and heart rate will be measured throughout the exercise. Type: threshold loading inspiratory muscle training (PowerBreath classic will be used.) Progression: will be studied at 10% of the re-measured MIP at the beginning of each week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Planned haematopoietic stem cell transplantation in the adult bone marrow transplant unit
- Between the ages of 18-65
- Under standard medical treatment, including immunosuppressives, antibiotics and other medications
- Ability to walk, co-operate and be clinically stable
- No history of orthopaedic, neurological, cardiac disorders
Key exclusion criteria (8 listed)
- Cognitive disorders
- Have orthopaedic or neurological diseases that may affect the assessment of physical fitness tests
- Having comorbidities such as asthma, COPD
- Conditions in which exercise training is contraindicated, such as acute bleeding, haemoglobin value <5 g/dl, platelet count ≤10000 mm3, high fever (body temperature >38◦C), severe pain, confusion, dizziness, nausea and vomiting
- Patients with pneumonia or any acute infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inspiratory Muscle TrainingInspiratory muscle training will be performed at 40% of MIP workload, 1 set of 8-10 diaphragmatic respirations for 15 minutes, with 5-10 seconds rest intervals between sets. 5 days a week, 2 sessions per day. | Other | 1. Inspiratory Muscle Training Group |
| Functional Inspiratory Muscle TrainingThis study investigates the integration of functional inspiratory muscle training (IMT) with conventional physiotherapy. Patients will perform inspiratory muscle training using the threshold loading technique with the POWERbreathe IMT device, combined with functional exercises. The functional IMT protocol will be administered face-to-face, 3 days a week, for 30 minutes per session over a 6-week period. Resistance on the IMT device will be set to 40% of the patient's maximal inspiratory pressure (MIP) and adjusted weekly based on measured MIP values. Exercises will be categorized into three progressive difficulty levels (easy, medium, and hard), with each stage lasting 2 weeks. Patients will inhale through the POWERbreathe IMT device during exercise movements and exhale during the return phase, ensuring simultaneous respiratory muscle activation and functional training. | Other | 2. Functional Inspiratory Muscle Training Group |
| Sham Inspiratory Muscle TrainingControl group will be performed at 10% of the MIP workload, 1 set of 8-10 diaphragmatic breaths for 15 minutes, with 5-10 seconds rest intervals between sets. 2 sessions per day, 5 days a week. | Other | 3. Control Group |
Primary outcome
Dyspnea Perception Measurement
Time frame: "Through study completion, an average of 1 year"
Dyspnea perception will be assessed using the Modified Borg Scale and the Modified Medical Research Council (MMRC) Dyspnea Scale. Modified Borg Scale: A subjective scale to assess dyspnea at rest and/or during activity. The scale ranges from 0-10, where 0 indicates no dyspnea and 10 indicates very severe dyspnea, reflecting the participant's perceived breathlessness. Modified MMRC Dyspnea Scale: This scale evaluates dyspnea during daily activities. It is graded as follows: 0: No dyspnea except for severe activity. 1. Dyspnea during fast walking or uphill climbing. 2. Dyspnea causes slower movement or stops on flat ground. 3. Dyspnea causes stopping after walking 100 meters or a few minutes. 4. Dyspnea occurs during dressing or undressing, preventing leaving the house. Unit of Measure: Modified Borg Scale: 0-10 points MMRC Dyspnea Scale: Grade 0-4
Cardiopulmonary Function Measurement
Time frame: "Through study completion, an average of 1 year"
Cardiopulmonary function will be assessed using the Cardiopulmonary Exercise Test (CPET) with the MES VO₂max Finder device (Poland), providing measurements of VO₂, VCO₂, VE, RER, and ventilatory threshold following ATS and ERS standards. Protocol: Pre-test Preparation: Avoid caffeine and vigorous exercise for 24 hours prior. Test Protocol: The Modified Bruce protocol with progressive increases in speed (2.7 to 8.8 km/h) and incline (0 to 20%) every 3 minutes. Vital Signs Monitoring: Heart rate, blood pressure, SpO₂, dyspnea, and fatigue monitored. Test Duration: 8-12 minutes, ending when two criteria are met (exhaustion, 90% max heart rate, RER ≥ 1.10, or blood lactate > 8.0 mmol/L). Cooldown: 3-minute cooldown post-test. Gas exchange analyzed breath-by-breath, with calibration per ATS/ERS guidelines. Unit of Measure: VO₂: mL/min VCO₂: mL/min VE: L/min RER: Ratio Ventilatory Threshold: L/min
Respiratory Muscle Strength Measurement
Time frame: "Through study completion, an average of 1 year"
Respiratory muscle strength will be assessed by measuring Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP) using the Micro Medical Micro RPM device (Rochester, UK), with measurements recorded in cmH₂O. MIP: Measured during maximal inspiration against a closed airway after full expiration. MEP: Measured during maximal expiration against a closed airway after full inspiration. Both MIP and MEP will be maintained for 1-3 seconds. Three measurements will be taken, and the best value will be recorded. Results will be expressed as a percentage of normal reference values adjusted for age and gender. Disposable, personalized mouthpieces and filters will be used to prevent infection, following ERS (2019) guidelines. Unit of Measure: MIP and MEP: cmH₂O, expressed as a percentage of normal reference values.
Respiratory Muscle Endurance Measurement
Time frame: "Through study completion, an average of 1 year"
Respiratory muscle endurance will be assessed using the Powerbreath Plus MR (HaB International Ltd., Southam, England), an inspiratory muscle training device employing a constant threshold load technique. The resistance of the device will be set at 60% of the participant's Maximum Inspiratory Pressure (MIP) value. During the test: The device will be placed in the participant's mouth, and the nose will be closed with a clip. The participant will be instructed to breathe through the device for a maximum of 10 minutes. Participants will be informed before the test that they can remove the device and stop the test if they feel excessive shortness of breath or discomfort. The time the participant is able to continue the test will be recorded in seconds. Unit of Measure: The unit of measure for this outcome is seconds for the duration the participant can continue the test.
Diaphragm Function and Thickness Measurement
Time frame: "Through study completion, an average of 1 year"
Diaphragm function and thickness will be assessed using Aplio XG ultrasonography (Toshiba, Japan) with patients in a supine position. Diaphragm Thickness: Measured using B-mode ultrasound with a 7 MHz transducer at the 9th intercostal space on the anterior axillary line at the end of expiration. Left hemidiaphragm imaging will not be performed due to anatomical limitations. Diaphragm Movement: Analyzed using M-mode ultrasonography with a 3.5 MHz transducer in a longitudinal semi-coronal plane. Excursion during calm breathing, deep breathing, and sniff test excursion will be assessed. The difference in diaphragm movement between inspiration and expiration will be calculated across three respiratory cycles. Unit of Measure: Diaphragm thickness and excursion will be expressed in millimeters (mm).
Inflammatory Markers Measurement
Time frame: "Through study completion, an average of 1 year"
Blood samples will be collected in blood collection tubes and centrifuged at 3,000 x g for 10 minutes to obtain the serum supernatant. The serum samples will be stored at -80°C until the day of the experiment. The following inflammatory markers will be measured: Proinflammatory markers: TNF-α and IL-6 Anti-inflammatory markers: IL-2 and IL-10 These markers will be measured using commercially available ELISA-based kits (Mybiosource Co., USA). Unit of Measure: The unit of measure will be expressed in pg/mL or ng/mL, depending on the kit's specifications for each marker.
Oxidative Stress Parameters Measurement
Time frame: "Through study completion, an average of 1 year"
Blood samples will be collected in blood collection tubes, centrifuged at 3,000 x g for 10 minutes to obtain serum supernatant, and stored at -80°C until analysis. Total Antioxidant Status (TAS): Measured by spectrophotometry (Thermo Scientific, Varioskan LUX, USA) using a commercial kit (Rel Assay Diagnostics, Turkey). Antioxidants reduce the ABTS radical to its colorless form, with absorbance at 660 nm correlating to TAS. Total Oxidant Status (TOS): Measured using a commercial kit (Rel Assay Diagnostics, Turkey) and spectrophotometrically (Thermo Scientific, Varioskan LUX, USA). Unit of Measure: TAS: mmol Trolox Equiv/L TOS: µmol H₂O₂ Equiv/L (or as per the kit specifications)
Muscle Biomarkers Measurement
Time frame: "Through study completion, an average of 1 year"
Serum CK-MM and CK-MB concentrations will be measured using ELISA-based commercial kits. Microwells pre-coated with monoclonal antibodies will capture the biomarkers, followed by detection using a biotin-conjugated antibody. After washing, HRP-conjugated avidin will be added, and TMB substrate will be used for colorimetric detection. Absorbance will be measured at 450 nm using a spectrophotometric plate reader (Thermo Scientific, USA). Blood samples (15 mL × 3 tubes) will be collected twice, before and after treatment, in gel biochemistry tubes at İstinye University laboratories. Serum will be obtained by centrifugation and stored at -80°C until analysis. In addition, CRP, hemoglobin, platelet, and albumin levels will be recorded from patient follow-up files. Unit of Measure: CK-MM and CK-MB concentrations: ng/mL (as per the ELISA kit specifications)
Pulmonary Function Test
Time frame: "Through study completion, an average of 1 year"
The pulmonary function test will be performed using a spirometer (Cosmed Pony FX, Italy) following ATS/ERS guidelines. The test will measure: Forced Vital Capacity (FVC) Forced Expiratory Volume in the First Second (FEV1) FEV1/FVC ratio Peak Expiratory Flow (PEF) Forced Expiratory Midflow Rate (FEF25-75%) The test will be conducted in a sitting position, with the best of three technically acceptable maneuvers demonstrating 95% agreement selected for analysis. Parameters will be expressed as a percentage of predicted values adjusted for age, height, and gender. Sterilization procedures, disposable, and personalized mouthpieces/filters will be used to prevent infection. Unit of Measure: FVC, FEV1, FEV1/FVC, PEF, FEF25-75%: Percentage of predicted values (adjusted for age, height, and gender)
4 secondary outcomes
Peripheral Muscle Strength Measurement
Time frame: "Through study completion, an average of 1 year"
Fatigue Perception Measurement
Time frame: "Through study completion, an average of 1 year"
Depression Measurement
Time frame: "Through study completion, an average of 1 year"
Quality of Life Measurement
Time frame: "Through study completion, an average of 1 year"
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2025.
- Individual participant dataSharing planned: No. No plans to share individual participant data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inspiratory Muscle Training and Functional Inspiratory Muscle Training in people with Hematopoietic Stem Cell Transplantation (HSCT) and Pulmonary Rehabilitation, run by Ceren Derya Gültekin at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ceren Derya Gültekin, MSc (+905383200141, cerenderya1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dyspnea Perception Measurement (time frame: "Through study completion, an average of 1 year"). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2025.