Effects of Controlled Breathing on Cardiorespiratory Variables in Multiple Myeloma

Efficacy of a Controlled Breathing and Therapeutic Exercise Program on Cardiorespiratory Variables in Patients With Multiple Myeloma

A randomized, parallel, double-blind, controlled, clinical trial. Two groups of participants will be included, both receiving a therapeutic exercise intervention and an educational session on the importance of proper breathing over a 6-week period. One of the groups will additionally perform a home-based controlled breathing exercise protocol. Pre- and post-intervention assessments (6 weeks) will be conducted, along with a follow-up evaluation 4 weeks after completion of the intervention. The goal is to determine the effectiveness of adding a controlled breathing exercise program to a therapeutic exercise intervention on cardiorespiratory variables in individuals with multiple myeloma.

Study Overview

• Status: Not yet recruiting
• Conditions: Breathing Exercises; Diaphragmatic Breathing; Multiple Myeloma (MM); Exercise Activity; Breathing Techniques; Heart Rate Variability (HRV)
• Intervention / Treatment: Other: Controlled breathing exercise protocol + therapeutic exercise + initial education session; Other: Therapeutic exercise + initial education session

Detailed Description

Randomized, parallel, double-blind, controlled clinical trial including participants with a confirmed medical diagnosis of multiple myeloma who are currently receiving active treatment with daratumumab and are under clinical follow-up by the Hospital Hematology Department.

Participants will be randomly assigned to one of two intervention groups:

• Control group: Therapeutic exercise + an initial educational session on proper breathing.
• Experimental group: Therapeutic exercise + an initial educational session on proper breathing + a home-based controlled breathing exercise protocol.

Both groups will undergo their respective intervention programs for 6 weeks. During each of the six weeks, participants will:

Perform three weekly sessions of mobility and muscle-strengthening exercises (two supervised on-site sessions and one home-based session). The on-site sessions will last 30-40 minutes and will be conducted at the Rehabilitation Department of Hospital 12 de Octubre in Madrid (a total of 12 on-site sessions, two per week). The weekly home-based session will consist of a structured session replicating the content and methodology of the supervised program.

Walk a minimum of 7,000 steps per day or 50 minutes per day, at least three days per week.

Participants assigned to the experimental group will additionally perform a controlled breathing protocol twice daily at home, following the recommendations of the principal investigator. Furthermore, they will complete two in-person controlled breathing training sessions, each lasting 5 minutes, at the hospital to ensure correct execution of the technique-one at the beginning of the intervention and one at its completion.

The variables to be assessed will include heart rate variability (HRV) indicators (SDNN, RMSSD, HF), heart rate, lower limb strength assessed using the 30-Second Sit-to-Stand Test (30STS), and estimated peak oxygen consumption (VO₂peak). All outcome measures will be evaluated at baseline, at the end of the 6-week intervention, and 4 weeks after completion of the intervention.

In addition, heart rate variability indicators and heart rate will be assessed immediately before and after the two in-person controlled breathing training sessions. as well as before and after an additional reinforcement session conducted four weeks after completion of the intervention. This will allow evaluation of the acute response of these variables to the breathing protocol, compared with participants in the control group, who will be instructed to breathe spontaneously, maintaining their habitual breathing pattern without any external guidance during the same time period.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isidro Fernández-López, PhD; Phone Number: +34625598970; Email: isidrofe@ucm.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Confirmed diagnosis of multiple myeloma, currently undergoing active treatment with daratumumab, and under clinical follow-up by the Hematology Department of HU12O.
• Explicit medical indication for supervised physical activity issued by the responsible hematologist and documented in the medical record.
• No scheduled hematopoietic stem cell transplantation within the 60 days following the planned start date of the intervention (verified through medical record review).
• Functional status of ECOG 0-2 (Eastern Cooperative Oncology Group), assessed by a healthcare professional from the Hematology Department, ensuring the ability to perform at least basic and light instrumental activities of daily living, including independent ambulation.
• Access to a smartphone with stable internet connection, required for monitoring and recording adherence to the intervention.
• Ability to provide written informed consent, demonstrating understanding of the study's nature, purpose, and procedures.

Exclusion Criteria:

• Medical risk contraindicating exercise or breathing techniques:

  • Clinically significant cardiovascular disease, including:decompensated heart failure, acute myocardial infarction within the past 3 months, clinically uncontrolled arrhythmias, unstable angina, acute-phase deep vein thrombosis or pulmonary embolism, pacemakers or cardiac devices whose monitoring parameters contraindicate supervised exercise according to cardiology.
  • Severe decompensated respiratory disease, such as acute exacerbation of COPD, severe respiratory insufficiency, or persistently low resting oxygen saturation < 90% (not correctable).

• High musculoskeletal or bone risk:

  • Extensive lytic bone lesions, high risk of pathological fracture, or unstable vertebral fracture, documented by imaging or based on the assessment of the Hematology/Traumatology specialist.
  • Uncontrolled pain that prevents safe participation in an exercise program.

• Hematologic or systemic conditions contraindicating exercise:

  • Severe anemia: hemoglobin < 9 g/dL in women or < 8 g/dL in men (latest laboratory test ≤ 14 days).
  • Active systemic infection contraindicating exercise, fever ≥ 38 °C, or neutropenia < 0.5 × 10⁹/L.
  • Severe cytopenias that, in the opinion of the hematologist, preclude moderate exercise.

• Functional or procedural limitations:

  • Inability to remain in the supine position for ≥ 5 minutes, required for part of the breathing intervention.
  • Confirmed pregnancy or reasonable suspicion of pregnancy.
  • Severe cognitive impairment, major psychiatric disorders, or neurological diseases that limit understanding of the procedures or safe participation.
  • Significant difficulty understanding the language (spoken or written) that prevents following essential instructions or completing validated questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapeutic exercise + initial educational session on proper breathing; Perform three weekly sessions of mobility and muscle-strengthening exercises (two on-site and one home-based) for 6 weeks. The home-based exercise program will consist of completing, once per week during the 6-week intervention, a structured session that replicates the logic and technique of the on-site program.; Walk a minimum of 7,000 steps/day or 50 minutes/day, three days per week.; To promote adherence to the protocol and standardize basic knowledge regarding the breathing technique, all participants will receive an initial educational session delivered on the first day of the on-site intervention. This session will include an introductory lecture and an explanatory leaflet outlining the fundamental principles of functional breathing and its relevance to the intervention.	Other: Therapeutic exercise + initial education session; In addition to the educational session on proper breathing, participants will perform: Three weekly sessions of mobility and muscle-strengthening exercises (two on-site and one home-based) for 6 weeks. The on-site sessions will last between 30 and 40 minutes and will take place at the Rehabilitation Department of Hospital 12 de Octubre in Madrid (a total of 12 on-site sessions-two per week). The home-based exercise program will consist of completing, once per week during the 6-week intervention, a structured session that replicates the logic and technique of the on-site program. A maximum of four absences from the on-site therapeutic exercise program will be allowed, and on those occasions the patient must register via the web application that they completed the prescribed home-based program.; Walk a minimum of 7,000 steps/day or 50 minutes/day, three days per week.
Experimental: Therapeutic exercise + initial education session + home-based controlled breathing exercise protocol; Participants will perform a controlled breathing protocol at home twice daily, at least five days per week, throughout the 6-week study period, following the recommendations of the principal investigator. Additionally, within this same group, two in-person controlled breathing training sessions, each lasting 5 minutes, will be conducted at the hospital.; Perform three weekly sessions of mobility and muscle-strengthening exercises (two on-site and one home-based) for 6 weeks. The home-based exercise program will consist of completing, once per week during the 6-week intervention, a structured session that replicates the logic and technique of the on-site program.; Walk a minimum of 7,000 steps/day or 50 minutes/day, three days per week.; All participants will receive an initial educational session and an explanatory leaflet outlining the fundamental principles of functional breathing.	Other: Controlled breathing exercise protocol + therapeutic exercise + initial education session; In addition to the therapeutic exercise protocol and the educational session on proper breathing, participants will perform a controlled breathing protocol at home twice daily, at least five days per week, throughout the 6-week study period, following the recommendations of the principal investigator. The goal is to integrate slow, gentle, diaphragmatic, nasal breathing into daily life. Additionally, within this same group, two in-person controlled breathing training sessions, each lasting 5 minutes, will be conducted at the hospital to promote correct execution of the technique, one at the beginning of the intervention and another at its completion. To promote adherence and ensure correct and consistent execution, participants will have access through the Web-App to two audio files containing guided breathing instructions and visualization exercises. These recordings were specifically developed for this project by a physiotherapist with more than 20 years of experience.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRV SDNN pre-postintervention	Two measurement systems will be used concurrently to assess HRV SDNN and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	Baseline measurement: obtained prior to initiation of the training protocol. Second measurement: obtained immediately upon completion of the 6-week protocol.Follow-up: one additional measurement four weeks after completing the intervention protocol.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRV SDNN In-person controlled breathing intervention	The standard deviation of normal R-R intervals (SDNN) is a heart rate variability (HRV) index that represents overall HRV activity in the time domain; higher values indicate greater overall HRV activity. This variable will be assessed before and after the two in-person 5-minute controlled breathing training sessions, as well as before and after an additional reinforcement session conducted four weeks after completion of the intervention. This design will allow evaluation of the temporal evolution of these variables in response to the breathing protocol, compared with participants in the control group, who will be instructed during the same time periods to breathe spontaneously, maintaining their usual breathing pattern without any external guidance. Two measurement systems will be used concurrently to assess HRV SDNN and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	-First measurement: before and after the first in-person breathing training session.-Second measurement (week 6): before and after the second in-person breathing training session.-Third measurement (week 10): before and after the reinforcement session
HRV RMSSD In-person controlled breathing intervention	The root mean square of successive differences between R-R intervals (RMSSD) is a heart rate variability (HRV) index that correlates with vagally mediated regulation. This variable will be assessed before and after the two in-person 5-minute controlled breathing training sessions, as well as before and after an additional reinforcement session conducted four weeks after completion of the intervention. This design will allow evaluation of the temporal evolution of these variables in response to the breathing protocol, compared with participants in the control group, who will be instructed during the same time periods to breathe spontaneously, maintaining their usual breathing pattern without any external guidance. Two measurement systems will be used concurrently to assess HRV RMSSD and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	-First measurement: before and after the first in-person breathing training session.-Second measurement (week 6): before and after the second in-person breathing training session.-Third measurement (week 10): before and after the reinforcement session.
HRV HF In-person controlled breathing intervention	High frequency (HF) is a heart rate variability (HRV) index that represents parasympathetic nervous system activity in the frequency domain. This variable will be assessed before and after the two in-person 5-minute controlled breathing training sessions, as well as before and after an additional reinforcement session conducted four weeks after completion of the intervention. This design will allow evaluation of the temporal evolution of these variables in response to the breathing protocol, compared with participants in the control group, who will be instructed during the same time periods to breathe spontaneously, maintaining their usual breathing pattern without any external guidance. Two measurement systems will be used concurrently to assess HRV HF and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	-First measurement: before and after the first in-person breathing training session.-Second measurement (week 6): before and after the second in-person breathing training session.-Third measurement (week 10): before and after the reinforcement session.
Heart Rate In-person controlled breathing intervention	This variable will be assessed before and after the two in-person 5-minute controlled breathing training sessions, as well as before and after an additional reinforcement session conducted four weeks after completion of the intervention. This design will allow evaluation of the temporal evolution of these variables in response to the breathing protocol, compared with participants in the control group, who will be instructed during the same time periods to breathe spontaneously, maintaining their usual breathing pattern without any external guidance. Two measurement systems will be used concurrently to assess HR and to evaluate agreement between methods. Heart rate (HR) will be assessed using the mean value obtained over the 5-minute recording period from both measurement systems employed. These two systems are: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	-First measurement: before and after the first in-person breathing training session.-Second measurement (week 6): before and after the second in-person breathing training session.-Third measurement (week 10): before and after the reinforcement session.
Heart Rate pre-postintervention	Heart rate (HR) will be assessed using the mean value obtained over the 5-minute recording period from both measurement systems employed. These two systems are: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	Baseline measurement: obtained prior to initiation of the training protocol. Second measurement: obtained immediately upon completion of the 6-week protocol.Follow-up: one additional measurement four weeks after completing the intervention protocol.
HRV RMSSD pre-postintervention	The root mean square of successive differences between R-R intervals (RMSSD) is a heart rate variability (HRV) index that correlates with vagally mediated regulation. Two measurement systems will be used concurrently to assess HRV RMSSD and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	Baseline measurement: obtained prior to initiation of the training protocol. Second measurement: obtained immediately upon completion of the 6-week protocol.Follow-up: one additional measurement four weeks after completing the intervention protocol.
HRV HF pre-postintervention	High frequency (HF) is a heart rate variability (HRV) index that represents parasympathetic nervous system activity in the frequency domain; lower values indicate anxiety or stress, whereas higher values suggest a state of relaxation. Two measurement systems will be used concurrently to assess HRV HF and to evaluate agreement between methods: Handheld portable electrocardiograph.; Heart rate and HRV monitor with chest-worn sensor (Polar H10).	Baseline measurement: obtained prior to initiation of the training protocol. Second measurement: obtained immediately upon completion of the 6-week protocol.Follow-up: one additional measurement four weeks after completing the intervention protocol.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower-Limb Strength	The 30-Second Sit-to-Stand test (30STS) will be used to assess lower-limb strength and endurance. This test has been employed in several studies involving oncology patients.	Information for this variable will be collected at three time points: at baseline, at the end of the intervention (6 weeks), and four weeks after completion of the protocol.
Estimated Peak Oxygen Consumption (VO₂peak)	The same test used to assess lower-limb muscle strength (30STS) will be employed to estimate peak oxygen consumption (VO₂peak). The 30STS has been shown to be a useful tool for estimating VO₂peak in patients with cancer. Its use may facilitate the evaluation and stratification of functional capacity in this population. The formula used to estimate VO₂peak will correspond to the equation known as ONCORE.	Information for this variable will be collected at three time points: at baseline, at the end of the intervention (6 weeks), and four weeks after completion of the protocol.

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Investigators: Study Director: Gustavo Plaza-Manzano, PhD, Faculty of Nursing, Physiotherapy and Podiatry. Universidad Complutense de Madrid

Publications and helpful links

General Publications

• Shahriari M, Dehghan M, Pahlavanzadeh S, Hazini A. Effects of progressive muscle relaxation, guided imagery and deep diaphragmatic breathing on quality of life in elderly with breast or prostate cancer. J Educ Health Promot. 2017 Apr 19;6:1. doi: 10.4103/jehp.jehp_147_14. eCollection 2017.
• Fournie C, Verkindt C, Dalleau G, Bouscaren N, Mohr C, Zunic P, Cabrera Q. Rehabilitation program combining physical exercise and heart rate variability biofeedback in hematologic patients: a feasibility study. Support Care Cancer. 2022 Mar;30(3):2009-2016. doi: 10.1007/s00520-021-06601-2. Epub 2021 Oct 12.
• Nicol JL, Chong JE, McQuilten ZK, Mollee P, Hill MM, Skinner TL. Safety, Feasibility, and Efficacy of Exercise Interventions for People With Multiple Myeloma: A Systematic Review. Clin Lymphoma Myeloma Leuk. 2023 Feb;23(2):86-96. doi: 10.1016/j.clml.2022.10.003. Epub 2022 Oct 22.
• Li J, Peng Y, Zhan D, Zhang Y, Yu S. Exercise interventions in patients with multiple myeloma: a scoping review. BMC Sports Sci Med Rehabil. 2025 Jun 9;17(1):148. doi: 10.1186/s13102-025-01193-4.
• Díaz-Balboa E, González-Salvado V, Rodríguez-Romero B, et al. Thirty-second sit-to-stand test as an alternative for estimating peak oxygen uptake and 6-min walking distance in women with breast cancer: a cross-sectional study. Support Care Cancer. 2022;30(10):8251-8260. doi:10.1007/s00520-022-07268-z
• Insulander P, Carnlöf C, Schenck-Gustafsson K, Jensen-Urstad M. Device profile of the Coala Heart Monitor for remote monitoring of the heart rhythm: overview of its efficacy. Expert Rev Med Devices. 2020;17(3):159-165. doi:10.1080/17434440.2020.1732814
• Luna-Alcala S, Espejel-Guzmán A, Lerma C, et al. Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab. Cardiooncology. 2024;10(1):32. doi:10.1186/s40959-024-00236-y

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Breathing; Breathing exercises; multiple myeloma; heart rate variability; Diaphragmatic breathing; Slow breathing; exercise activity
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Immune System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Respiration Disorders; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Signs and Symptoms, Respiratory; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Respiratory Insufficiency; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Respiratory Aspiration; Multiple Myeloma; Hypoventilation; Therapeutics; Physical Therapy Modalities; Patient Care; Rehabilitation; Aftercare; Continuity of Patient Care; Exercise Therapy
• Other Study ID Numbers: Cardiorespiratory Mieloma

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No