Clinical trial NCT04950452: Exercise Training to Promote Resilience to Chronic Lymphocytic Leukemia
Official title: Exercise Training to Promote Resilience to Chronic Lymphocytic Leukemia in Older Adults by Enhancing Physical and Immunological Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Chronic Lymphocytic Leukemia
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2021-07-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: PURPOSE: The purpose of the study is to determine the effects of 12-weeks of exercise training on physical reserve, as measured by aerobic capacity, strength and physical function, in patients with CLL. Further, it is our aim to assess relationships with changes in physical reserve and resilience to the patient's cancer, as measured by immune cell counts, tumor cell killing and antibacterial functions.

DESIGN: Subjects will have confirmed treatment naïve CLL. Subjects will be assigned to either a 12-week control (no supervised exercise) or an intervention (HIIT) group. Before and after the 12 week program subjects will undergo several tests including: 1) a maximal treadmill test, 2) body composition, 3) muscle strength and endurance, 4) physical activity levels, 5) blood measures (e.g. immune and inflammatory functions). Subjects in the HIIT group will complete a 12-week supervised exercise training program consisting of HIIT and strength training.

DATA ANALYSES \& SAFETY ISSUES: This is a pilot study, with the goal of assessing whether exercise training causes a change in aerobic fitness (VO2peak), muscle function, and immunological measures. Vo2peak will be measured by a cardiopulmonary exercise test, muscle function will be measured by strength tests, and immunological functions will be measured from blood samples. For outcomes, group change differences from baseline to 12-weeks will be compared by ANCOVA. The data will be used to provide power calculations for future grant proposals. High Intensity Interval Training is a very safe exercise modality. The regular use of vigorous intensity exercise intervals have been used extensively in exercise training. In fact, the exercise intervals will start at levels lower and will be of shorter duration than were used during the maximal exercise test. They will then be carefully and slowly made to be more challenging as each subject is able to safely tolerate.

HYPOTHESIS: The investigators hypothesize that HIIT will be a feasible exercise intervention for people with CLL and will result in improvements in markers of health and fitness.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CLL as per the International Workshop on CLL Guidelines.
* Male or female ≥ 18 years of age
* No history of prior treatment of CLL
* Able to walk on a treadmill or cycle on an ergometer
* Pass the CPET evaluation of aerobic fitness and cardiac health

Exclusion Criteria:

* Clinical evidence of significant disease progression with first line therapy expected within 6 months
* Corticosteroid therapy initiated less than 7 days prior to study entry. Prednisone 10mg or less or equivalent is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.
* Malignancy within 3 years of study enrollment requiring intervention except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA stable
* Absolute contra-indications to exercise: Recent (\<6 months) acute cardiac event unstable angina, uncontrolled dysrhythmias causing symptoms or hemodynamic compromise, symptomatic aortic stenosis, uncontrolled symptomatic heart failure, acute pulmonary embolus, acute myocarditis or pericarditis, suspected or known dissecting aneurism and acute systemic infection.
* Significant orthopedic limitations, musculoskeletal disease and/or injury. Due to the nature of the study, persons with known joint, muscle or other orthopedic limitations that restrict physical activity may be excluded.
* Type I diabetes mellitus or uncontrolled Type II diabetes mellitus (HbA1c \>7%), or chronic obstructive pulmonary disease
* Uncontrolled blood pressure (≥180/90) at rest during screening and confirmed on repeat manual measurement
* Unable to travel to fitness center or comply with other study requirements
* Known concurrent HIV, Hepatitis B or Hepatitis C

Primary outcomes:
measure: Change in VO2peak as measured by cardiopulmonary exercise test
timeFrame: Baseline to 12-weeks
Secondary outcomes:
measure: Change in lymphocyte doubling rate (LDR) as measured by blood test
timeFrame: Baseline to 12-weeks
measure: Change in muscle strength as measured by a strength test
timeFrame: Baseline to 12-weeks
measure: Change in muscle endurance as measured by a muscle endurance test
timeFrame: Baseline to 12-weeks
measure: Change in neutrophil to lymphocyte ratio (NLR) as measured by blood test
timeFrame: Baseline to 12-weeks
measure: Change in lymphocyte to monocyte ratio (LMR) as measured by blood test
timeFrame: Baseline to 12-weeks
measure: Change in natural killer cell killing of tumor cell lines as measured by flow cytometry
timeFrame: Baseline to 12-weeks
measure: Change in neutrophil killing of E.coli as measured by flow cytometry
timeFrame: Baseline to 12-weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: David Bartlett, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Andrea Sitlinger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Artese AL, Sitlinger A, MacDonald G, Deal MA, Hanson ED, Pieper CF, Weinberg JB, Brander DM, Bartlett DB. Effects of high-intensity interval training on health-related quality of life in chronic lymphocytic leukemia: A pilot study. J Geriatr Oncol. 2023 Jan;14(1):101373. doi: 10.1016/j.jgo.2022.09.002. Epub 2022 Sep 9.
citation: MacDonald G, Sitlinger A, Deal MA, Hanson ED, Ferraro S, Pieper CF, Weinberg JB, Brander DM, Bartlett DB. A pilot study of high-intensity interval training in older adults with treatment naive chronic lymphocytic leukemia. Sci Rep. 2021 Nov 30;11(1):23137. doi: 10.1038/s41598-021-02352-6.