Clinical trial NCT03779867: Acute Exercise Intervention in Breast Cancer Survivors
Official title: Acute Effects of Exercise on Breast Cancer Biomarkers (ACE) Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Breast Carcinoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: Breast Cancer Research Foundation
First posted: 2018-12-19
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This trial studies how a 45-minute bout of acute exercise in women with a history of breast cancer can affect factors associated with breast cancer and help doctors learn more about how exercise can help prevent breast cancer.

In an earlier part of the study, investigators looked at the effects of the same intervention in women without a history of cancer.

Detailed description: OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants undergo a moderate-intensity acute exercise bout over 45 minutes.

ARM II: Participants rest by sitting for 45 minutes.

EXTENSION: After completion of initial study recruitment and data collection, an extension was approved in 2023.

EXTENSION OUTLINE: Participants are randomized to 1 of 2 arms.

EXTENSION ARM I: Participants exercise on a stationary bike for 45 minutes.

EXTENSION ARM II: Participants rest by sitting for 45 minutes.

Eligibility criteria: Current Inclusion Criteria (for Extension participants):

* Female
* History of Stage 0-IIIc breast cancer, diagnosed within the last 5 years
* Completed primary treatment at least 6 months ago
* Able to attend 2 clinic visits at the Fred Hutch Prevention Center for approximately 2.5 hours at a time
* Aged 36-75 years. Younger women will be excluded because a sizable proportion may remain premenopausal and will resume menstruation within 2 years of chemotherapy completion.
* Postmenopausal (no menstrual periods in the previous 12 months either naturally, or as a consequence of treatment)
* All race and ethnic groups are eligible for the study
* Able to perform all study requirements, including attendance at clinic visits and capable of responding to questionnaires and clinic and exercise facility instructions in English
* Willing to consent to release of medical records for their breast cancer diagnosis and treatment
* If a patient has received a cardiotoxic therapy (e.g., Adriamycin, Herceptin), clearance of their oncologist to participated in this study will be required.

Completed Inclusion Criteria (for participants enrolled prior to Extension portion of study):

* Resident in greater Seattle metropolitan area (King County), Pierce or Snohomish Counties
* Healthy
* Able to perform all study requirements, including attendance at clinic visits and capable of responding to questionnaires and clinic and exercise facility instructions in English
* Willing to be randomized
* Capable of providing informed consent

Current Exclusion Criteria (for Extension participants):

* Family history of breast cancer
* If known, BRCA 1/2 mutation carrier
* If known, Li-Fraumeni Syndrome
* Personal history of cancer other than breast: exceptions are non-melanoma skin cancer and cervical neoplasia (CIN)
* Serious health conditions including diabetes, renal disease (e.g., chronic kidney disease), liver disease (e.g., cirrhosis, chronic liver failure), chronic lung disease (COPD, moderate or severe persistent asthma), auto-immune disease requiring oral or inhaled medication, congestive heart failure, or other condition likely to interfere with ability to exercise at moderate levels and undergo biosampling, or likely to interfere with study outcomes.
* Fasting glucose fingerstick \>126 mg/dL
* Taking any medications to treat high blood sugar such as metformin
* Contraindications for exercise testing (29) including: recent (within 6 months) cardiac event (MI, pulmonary edema, myocarditis, pericarditis), unstable angina, uncontrolled arrhythmia, third degree heart block, left bundle branch block, acute congestive failure, recent (within 6 months) pulmonary/systemic embolus, severe electrolyte abnormality, deep vein thrombosis, uncontrolled hypertension (systolic \> 200, diastolic \> 100), orthostatic hypotension, moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, history of cardiac arrest or stroke, or as assessed by the physician assistant during the physical exam.
* History of clotting disorders
* Unable or unwilling to stop aspirin or NSAIDs for 48 hours before and after the procedure
* Allergy to anesthetics or local anesthetics
* Long term use of warfarin or similar medications
* Use of medications that could affect exercise ability, blood biomarkers, or muscle biomarkers, including weight loss medications, statins, oral beta-blockers, performance-enhancing drugs, metformin or other diabetic drug, and oral corticosteroids.
* Use of any sex hormones (estrogen, progesterone, testosterone or other androgens, for the previous 3 months) of any type including oral, creams, vaginal creams or inserts, patches, implants). Participants will be allowed to be on maintenance anti-estrogen therapy - e.g., tamoxifen, aromatase inhibitors
* Consumption of (on average) more than 2 alcoholic drinks per day
* Current use of any tobacco products including smoking, vaping, chew, nicotine patches
* Frequent marijuana use (\>1 per month)
* Current participation in another randomized controlled trial

Completed Exclusion Criteria (for participants enrolled prior to Extension portion of study):

* Pregnant in past 3 months
* Lactating
* Premenopausal women: irregular menstrual periods for the previous 6 months; no use of oral contraceptives for the previous 3 months, no use of hormone implants or intrauterine device (IUD) for in the previous year, no use of other sex hormones including testosterone or other androgens for the previous 3 months
* Postmenopausal women: no use of any sex hormones (estrogen, progesterone, testosterone or other androgens, for the previous 3 months) of any type including oral, creams, vaginal creams or inserts, patches, implants
* Current use of any tobacco products including smoking, vaping, chew, nicotine patches
* History of diabetes mellitus, or fasting glucose fingerstick ≥ 126 mg/dL
* Taking any medications to treat high blood sugar such as metformin
* Personal history of invasive or in situ breast cancer
* Personal history of cancer other than breast: exceptions are non-melanoma skin cancer and cervical neoplasia (CIN)
* ≥ 2 alcoholic drinks/day
* Contraindications to exercise
* Abnormalities on screening physical that contraindicate participation
* Contraindications for entry into a research exercise program: recent (within 6 months) myocardial infarction, pulmonary edema, myocarditis, pericarditis, unstable angina, pulmonary embolism, deep vein thrombosis, uncontrolled hypertension (systolic \> 200, diastolic \> 100), orthostatic hypotension, moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, left bundle branch block, history of cardiac arrest or stroke
* Frequent marijuana use (\> 1 per month)
* Alcohol or drug abuse, significant mental illness (as assessed by study staff impression)
* History of clotting disorders (muscle-biopsy sub study)
* Unable or unwilling to stop aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) for 48 hours before and after the procedure (muscle-biopsy sub study)
* Allergy to anesthetics or local anesthetics (muscle-biopsy sub study)
* Long term use of warfarin or similar medications (muscle-biopsy sub study)

Primary outcomes:
measure: Mean change in homeostatic model assessment of insulin resistance (HOMA-IR)
timeFrame: Baseline up to 45 minutes
measure: Mean change in HOMA-IR
timeFrame: Baseline up to 105 minutes
measure: Change in insulin level
timeFrame: Baseline up to 45 minutes
measure: Change in insulin level
timeFrame: Baseline up to 105 minutes
measure: Change in glucose level
timeFrame: Baseline up to 45 minutes
measure: Change in glucose level
timeFrame: Baseline up to 105 minutes
measure: Change in Vascular Endothelial Growth Factor (VEGF) level
timeFrame: Baseline up to 45 minutes
measure: Change in VEGF level
timeFrame: Baseline up to 105 minutes
measure: Change in Irisin level
timeFrame: Baseline up to 45 minutes
measure: Change in Irisin level
timeFrame: Baseline up to 105 minutes
measure: Change in Plasminogen activator inhibitor type-1 (PAI-1) level
timeFrame: Baseline up to 45 minutes
measure: Change in PAI-1 level
timeFrame: Baseline up to 105 minutes
Secondary outcomes:
measure: Effects of exercise on HOMA-IR in normal-weight participants
timeFrame: At 45 minutes
measure: Effects of exercise on HOMA-IR in overweight/obese participants
timeFrame: At 45 minutes
measure: Change in C-reactive protein (CRP)
timeFrame: Baseline up to 105 minutes
measure: Change in Interleukin (IL)-6
timeFrame: Baseline up to 105 minutes
measure: Change in Monocyte chemotactic protein (MCP)-1
timeFrame: Baseline up to 105 minutes
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Anne McTiernan
role: PRINCIPAL_INVESTIGATOR
References: