Exercise, Cancer and Cognition: The ECCO-Study

Sponsor

Johannes Kepler University of Linz (Other)

Overall Status

Recruiting

CT.gov ID

NCT04789187

Collaborator

German Sport University, Cologne (Other), University of Graz (Other), Charite University, Berlin, Germany (Other), Charles University, Czech Republic (Other)

126

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The "ECCO"-study evaluates the efficacy of simultaneous controlled exercise during neo/-adjuvant chemotherapy in breast cancer patients and its effects on neurocognition.

In this study the investigators examine the benefits of the individualized high intensity training program on a cancer related cognitive impairment.

Changes in patients' cognition are evaluated by neuropsychological testing. Possible structural changes are detected with MRI volumetry. Biomarkers connected to Cancer Related Cognitive Impairment (CRCI) and chemotherapy related inflammatory processes which impair cognition, respectively, will be assessed.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Procedure: High-Intensity-Interval-Training Procedure: General Physical Activity Recommendations	N/A

Detailed Description

Background: Epidemiological research indicates that increased levels of physical activity are associated with decreased breast cancer risk and mortality. Thereby, exercise programs can substantially increase patients' quality of life during and after treatment. Up to 80% of breast cancer patients demonstrate a decrease in their cognitive capacity, summarized as the symptom-complex "Cancer Related Cognitive Impairment (CRCI)". Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory and executive functions. In about 35% of affected patients, cognitive symptoms persist for months, or even years, after completion of medical treatment, impairing daily functioning, limiting ability to return to work and decreasing overall quality of life. Recent studies indicate a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity therefore as a potential supportive care option is increasing. Anyhow, evidence for positive effects of exercise on CRCI is still lacking.

Patients and Methods: This prospective, two-arm, 1:1 randomized, controlled trial aims to investigate the influence of high-intensity training interventions accompanying neo/-adjuvant chemotherapy on CRCI in 126 patients with early breast cancer on cognitive performance measured by the California Verbal Learning Test (CVLT). Secondary endpoints include subjective markers and tests for cognitive performance and inflammatory biomarkers as TNF-α, IL-6, IL-1α, IL-1ß which are suspected to be involved in the pathogenesis of CRCI. As cognitive impairments are believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy, head MRIs and hippocampal volume measurements will be performed. In addition to a heart rate controlled home-based endurance and strength training for one year, participants in the intervention group will perform a supervised high-intensity interval training (HIIT) exercise program at least once a week. This study will help to clarify whether a long-term supervised exercise intervention program affects CRCI in breast cancer patients and help to reason underlying mechanisms and the pathogenesis of the chemobrain.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

126 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Controlled TrialRandomized Controlled Trial

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Pseudonymization

Primary Purpose:

Supportive Care

Official Title:

Randomized Controlled Trial of Simultaneous Exercise During Neo-/Adjuvant Chemotherapy in Breast Cancer Patients and Its Effects on Neurocognition

Actual Study Start Date :

Dec 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: Exercise intervention arm	Procedure: High-Intensity-Interval-Training Defined exercise program up to four times per week including high-intensity-interval-training for one year of active study intervention.
Placebo Comparator: Arm B: Control arm	Procedure: General Physical Activity Recommendations Patients will be given general physical activity recommendations during chemotherapy.

Arm

Intervention/Treatment

Active Comparator: Arm A: Exercise intervention arm

Procedure: High-Intensity-Interval-Training

Defined exercise program up to four times per week including high-intensity-interval-training for one year of active study intervention.

Placebo Comparator: Arm B: Control arm

Procedure: General Physical Activity Recommendations

Patients will be given general physical activity recommendations during chemotherapy.

Outcome Measures

Primary Outcome Measures

Cognition [12 month]
The primary endpoint is measured by the changes in the total score of the California Verbal Learning Test (CVLT), measured 12 months after baseline assessment. Total points of the score are 176 pts., with less points indicating a worse outcome/ cognitive impairment and more points a better outcome/ cognitive function.

Secondary Outcome Measures

Hippocampal Volume [12 month]
Devation of hippocampal volume measured 12 months after baseline assessment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed breast cancer and planned neo- and adjuvant chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Age 18 - 70 years
Adequate hematologic functions 28d prior to randomization (Platelet count over 50 G/L, Hemoglobin over 8 g/dL)
Able to perform exercise according to protocol
Signed informed consent prior to randomization
Fluid in German

Exclusion Criteria:

Significant comorbid conditions precluding participation in a physical activity program (investigators decision)
Anamnestic cognitive impairment or psychological disorders
Disabled patients unable to participate in the physical activity program or performing cognitive tests
Vigorous physical activity of >300 minutes weekly within the last year before diagnosis of breast cancer 8.3
Patients unwilling to complete endurance exercise or complete all questionnaires related to the study
Past or current history of other malignant neoplasms other than breast cancer in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
Clinically significant cardiovascular disease (including myocardial infarction < 6 month before randomization, unstable angina, symptomatic congestive heart failure NYHA II-IV, serious uncontrolled cardiac arrhythmia, preexcitation syndromes (eg Wolff-Parkinson-White-Syndrome), high grade or complete AV-Block, left bundle branch block, permanent pacemaker stimulation, uncontrolled hypertension (systolic blood pressure >160 mmHg), aortic valve stenosis, moderate to high-grade valve disease, endo-, myo-, pericarditis, acute aortic dissection, acute pulmonary embolism, acute phlebothrombosis of the lower extremity
Current pregnancy or plans to become pregnant within the next year after study entry (Pregnancy tests are included in clinical routine before every chemotherapy)
Signs of severe morphological brain damage in the baseline screening