Cancer Of the BReast Asanas Study (COBRA) (COBRA)

The Effect of Yoga on Endocrine Therapy Induced Musculoskeletal Symptoms in Women With Breast Cancer: the COBRA Study

Rationale: Women with hormone-receptor positive breast cancer are usually prescribed endocrine therapy for a period of 5-10 years. This treatment reduces the risk of recurrence and improves overall survival in these women. Musculoskeletal complaints are a common (~50%) negative consequence of endocrine treatment, which affects daily functioning and quality of life. These symptoms frequently result in early treatment discontinuation, which is associated with shorter disease-free survival. Musculoskeletal complaints are often pharmacologically treated with limited effect and accompanied by side-effects. Therefore, interventions to counteract musculoskeletal complaints are urgently needed in this population. A potential non-pharmacological option is yoga. In patients with osteoarthritis, there is emerging evidence that yoga is effective to reduce pain and stiffness and improve function. Yoga as treatment for musculoskeletal complaints that are associated with endocrine treatment is rarely investigated and mainly in small studies.

Objective: The objective of the proposed study is to assess the effectiveness of a 4-month yoga program compared to a waiting list control group on musculoskeletal complaints in women with hormone-positive stage I-III breast cancer receiving endocrine treatment who report musculoskeletal complaints.

Study design: The COBRA study is a randomized controlled trial with two study arms: a yoga- and a waiting list control group.

Study population: For this study, 140 women with oestrogen-receptor positive stage I-III breast cancer on endocrine treatment (aromatase inhibitors or Tamoxifen; >4 months) will be recruited. These women experience musculoskeletal complaints (>3 months) which started or exacerbated after initiation of endocrine treatment. Furthermore, eligible women did not practice yoga in the last six months and are not planning to start yoga and are not highly physically active (i.e., >150 minutes per week moderate-vigorous exercise).

Intervention: The intervention consists of two one-hour sessions/week supervised yoga and once a week 30-minute yoga exercises at home. The 4-month yoga program will be an active form of yoga, such as Easy Vinyasa yoga, which is characterized by continuous slow movements linked with breathing. The waiting list control patients will be offered an online yoga program after the 4-month study period.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Behavioral: live yoga; Behavioral: live remote yoga

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Evelyn Monninkhof, Dr.; Phone Number: +31623786177; Email: e.monninkhof@umcutrecht.nl
• Study Contact Backup: Name: Stefanie Veenhuizen, MSc; Phone Number: +31631119129; Email: s.g.a.veenhuizen@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 85500 3508 GA
    • Recruiting
    • University Medical Center Utrecht (UMC Utrecht)
    • Contact: Stefanie Veenhuizen, MSc; Phone Number: +31 6 31 11 91 29; Email: s.g.a.veenhuizen@umcutrecht.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be diagnosed with oestrogen-receptor positive stage I-III breast cancer,
• Use of aromatase inhibitors or Tamoxifen (>4 months and will continue using it for at least six months),
• Have finished primary treatment (chemotherapy, radiotherapy, surgery) for at least 12 weeks,
• Experience musculoskeletal complaints (>3 months, which are at least mild in severity (i.e., score of ≥ 3 for worst pain item of a modified version of the Brief Pain Inventory [BPI](16, 42))., which started or exacerbated after initiation of endocrine treatment,
• Be stabilized on menopausal symptom medication or antidepressants for at least three months and three weeks, respectively, if applicable, and
• Be able to read, speak and understand Dutch or English.

Exclusion Criteria:

• Too physically active (i.e., >150 minutes/week of self-reported moderate-to-vigorous or leisure and sports activities)
• Following (during the last 6 months), or planned to follow yoga classes on a structural base
• Following, or planned to follow, a structured psychological intervention during the intervention period, i.e., cognitive behavioral therapy, or unstable on psychotropic medication
• Participated in the intervention group of an exercise study during breast cancer treatment
• Any circumstances that would impede ability to give informed consent or adherence to study requirements as determined by the study team
• More than 3 weeks not able to attend training sessions during the intervention period
• A body mass index (BMI) of >35 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: yoga group; following live yoga classes twice a week and using yoga video's at home once a week	Behavioral: live yoga; following live yoga classes twice a week and using yoga video's at home once a week
Other: control group; Waiting list control group. The control group will be offered live remote yoga classes after the intervention period	Behavioral: live remote yoga; The control group will be offered live remote yoga classes after the intervention period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Musculoskeletal complaints	Worst of joint pain and stiffness/joint pain and stiffness severity/joint pain and stiffness interference assessed by the modified version of the BPI. The 14-item questionnaire result in three domain scores: worst pain/stiffness, pain/stiffness severity, and pain/stiffness interference over the past week, on a scale of 0 to 10. All these three domain scores of the BPI will be primary outcomes which will be tested sequentially to preserve an alpha of 0.05. The order of the sequential testing is: 1) worst pain/stiffness, 2) pain/stiffness severity and 3) pain/stiffness interference.	Baseline, at 4 and 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower extremity joint complaints	Using the WOMAC questionnaire	Baseline, at 4 and 8 months
Upper extremity musculoskeletal complaints	Using the DASH questionnaire	Baseline, at 4 and 8 months
Menopausal symptoms	Using the FACT-ES questionnaire	Baseline, at 4 and 8 months
Fatigue	Using the MFI questionnaire	Baseline, at 4 and 8 months
Sleep	Using the PSQI questionnaire	Baseline, at 4 and 8 months
Anxiety and depression	Using the Hospital Anxiety and Depression Scale (HADS) where anxiety and depression are measured separately on a scale from 0-7 (Normal), 8-10 (borderline abnormal) and 11-21 (abnormal).	Baseline, at 4 and 8 months
Blood markers	Inflammatory markers (Interleukin-6 and Interleukin-IB, tumor necrosis factor alpha (TNF-alpha) and high-sensitive C-reactive protein (hsCRP). At the end of the study we will conduct a literature review to identify the most promising biomarkers.	Baseline and at 4 months
Physical strength	Hand grip strength using a handgrip dynamometer. The best of three attempts will be recorded.	Baseline and at 4 months
Physical strength	Leg press using a hypothetical 1-RM test	Baseline and at 4 months
Physical fitness	Steep ramp test using a cycle ergometer	Baseline and at 4 months
Vital signs	Blood pressure and resting heart rate	Baseline and at 4 months
Anthropometrics	Weight and height will be combined to report BMI in kg/m^2. Waist- and hip circumference.	Baseline and at 4 months
Safety of the yoga intervention	(Serious) adverse events potentially related to the intervention	0-8 months (whole study period)
Compliance with endocrine treatment	Self-reported with a diary	0-8 months (whole study period)
Health-related Quality of Life (HRQoL)	Using the QLQ-C30 that has functional scales, symptom scales and a global quality of life (QOL) score. A high score for a functional scale represents a high/ healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.	Baseline, at 4 and 8 months
Health-related quality of life (HRQoL)	Using the BR45. The QLQ-BR45 incorporates nine multi-item scales to assess body image, sexual functioning, breast satisfaction, systemic therapy side effects, arm symptoms, breast symptoms, endocrine therapy symptoms, skin mucosis symptoms, endocrine sexual symptoms. All items are scored 1 to 4.	Baseline, at 4 and 8 months
Cognitive functioning	Using the Amsterdam Cognition Scan	Baseline and at 4 months
Cognitive functioning	Using the FACT-COG	Baseline, at 4 and 8 months
Physical activity	Using the Short Questionnaire to Assess Health-enhancing physical activity (SQUASH). Physical activity is measured in minutes per week.	Baseline, at 4 and 8 months
Physical strength	Plank position holding time test for core strength	Baseline and at 4 months
Physical fitness	Balance is measured with the Short-Form Fullerton Advanced Balance (S-FAB) scale. This scale consists of four items: stepping up onto and over a 6-inch bench, a tandem walk, standing on one leg, and standing on foam with the eyes closed. The items are rated from 0 (unable to complete the task) to 4 (completed the task perfectly), and the scores are summed up to a total score (0-16).	Baseline and at 4 months
Use of pain medication	Assessed with the BPI, questioned during the baseline and T1 visit, and self-reported with a diary	0-8 months (whole study period)
Qualitative outcome	Patient and teacher experiences with in-depth interviews	During or after the study

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: World Cancer Research Fund International
• Investigators: Study Director: Anne May, Prof. Dr., UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 24-054/G; NL86325.041.24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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