Effects of Controlled Breathing on Cardiorespiratory Variables in Multiple Myeloma

Official title

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

Overview

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.

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.

Interventions

• 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 min
• 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 interventi

Primary outcome measures

• HRV SDNN pre-postintervention [Time frame: 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 (7)

• HRV SDNN In-person controlled breathing intervention [Time frame: -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 [Time frame: -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 [Time frame: -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 [Time frame: -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 [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Diaz-Balboa E, Gonzalez-Salvado V, Rodriguez-Romero B, Martinez-Monzonis A, Pedreira-Perez M, Cuesta-Vargas AI, Lopez-Lopez R, Gonzalez-Juanatey JR, Pena-Gil C. 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 Oct;30(10):8251-8260. doi: 10.1007/s00520-022-07 PMID 35819522
• Insulander P, Carnlof 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 Mar;17(3):159-165. doi: 10.1080/17434440.2020.1732814. Epub 2020 Feb 26. PMID 32101067
• Luna-Alcala S, Espejel-Guzman A, Lerma C, Leon P, Guerra EC, Fernandez JRE, Martinez-Dominguez P, Serrano-Roman J, Cabello-Ganem A, Aparicio-Ortiz AD, Keirns C, Lerma A, Ana-Bayona MJS, Espinola-Zavaleta N. Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab. Cardiooncology. 2024 May 29;10(1):32. doi: 10.1186/s40959- PMID 38812020
• 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. PMID 40490782
• 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. PMID 36450625
• 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. PMID 34636946
• 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. PMID 28546966

Identifiers

NCT: NCT07376733 · Cardiorespiratory Mieloma

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗