Clinical trial NCT05116137: The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors
Official title: The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors (RESIST)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Glioblastoma Multiforme of Brain
Brain Cancer
Keywords: Exercise
Circuit-based resistance training
Intervention
Myopathy
Functional status
Quality of life
Randomized controlled trial
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Society (CCS)
First posted: 2021-11-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCTwith 1:1 allocation to intervention or wait-list control
Primary purpose: SUPPORTIVE_CARE

Brief summary: Glioblastoma patients are confronted with a debilitating disease associated with a low survival rate and poor quality of life. The goal of this study will be to reach a largely underrepresented population in the exercise literature and explore the role of a tailored circuit-based resistance training program on functional fitness (i.e., ability to carry out tasks of daily living) and associated health outcomes (e.g., quality of life) for GBM patients on active treatment.

Detailed description: PROBLEM: Glioblastoma multiforme (GBM) is the most common brain malignancy accounting for approximately 48% of all brain tumors. GBMs are highly vascular and can cause vasogenic brain edema and mass effect, which can worsen the neurologic symptoms associated with the disease. Corticosteroids (i.e., Dexamethasone; DEX) are the treatment of choice to reduce vasogenic edema and intercranial pressure associated with GBM. However, the use of steroids comes at a cost. High dose steroid therapy and/or long-term use results in muscle myopathy (i.e., muscle weakness) in 10-60% of GBM patients, significantly reducing functional ability as well as quality of life (QOL). Thus, adjuvant therapies are needed to help patients maintain their functional ability and QOL. There is a wealth of evidence to support the use of exercise as an adjuvant therapy to improve functional ability as well as help manage treatment-related symptoms. Resistance training (RT) has been shown to increase muscle mass, strength, and functional ability in aging adults and several cancer populations. While limited, studies in GBM have shown that exercise is safe and feasible for this population and that it can improve functional performance. However, no specific research has been performed to determine whether RT can be successfully used in GBM to prevent or reduce steroid induced muscle myopathy. Therefore, the primary purpose of this study is to establish whether an individualized circuit-based RT program will improve functional fitness for patients on active treatment and receiving steroids.

METHODS: This is a two-armed randomized control trial with repeated measures. Thirty-eight adult (18+ years) patients diagnosed with either primary or secondary GBM who are scheduled to receive standard radiation and concurrent adjuvant Temozolomide chemotherapy post-surgical debulking as well as received any dose of DEX will be recruited through the neuro-oncology clinic and the QEII Cancer Center. Patients will be randomly allocated to a standard of care group (SOC) or SOC+RT group (EX). Those in the SOC group will be advised to maintain an active lifestyle for the 12-week intervention whereas those in the EX group will receive a personalized 12-week circuit-based RT program. This program will consist of 3-4 supervised RT sessions/wk. During each session participants will perform a RT program that is comprised of 3 circuits. Each circuit will include 3 sets of 3 different exercises. Each exercise set will be 1 minute in duration (20 seconds/exercise) with 1 minute of rest between sets. Initial exercise intensity will be light and will increase throughout the program based on the participant's progress. All exercise programs will be designed and supervised by a Clinical Exercise Physiologist (CEP). The primary outcome measure for the study is functional performance which will be assessed using the Short Physical Performance Battery and hand grip strength. Secondary outcome measures will include body composition, aerobic fitness, physical activity levels, general health, QOL, fatigue, and cognitive function. All measures will be assessed pre/post-intervention. Safety and exercise adherence will be assessed throughout the study.

ANALYSIS: Descriptive statistics will be used to describe the population, accrual, program adherence and safety. Outcome data will be analyzed using an intention to treat approach. All participants will be entered into a mixed effects model with participant group assignment (EX, SOC) at randomization and timepoint (pre- and post-test) as fixed factors and participant entered as a random factor. Due to feasibility in recruiting participants in the allotted time, the study will not be fully powered to detect sex-based differences; however, effect sizes associated with the intervention will be calculated and presented separately for each sex.

SIGNIFICANCE: This study will demonstrate the not only is RT safe and feasible for those with GBM, but that it also significantly improves functional status by protecting against myopathy. This will help GBM patients maintain their independence which could lead to marked improvements in QOL.

Eligibility criteria: Inclusion Criteria:

* histologically confirmed diagnosis of either primary or secondary GBM
* received any dose of DEX
* Karnofsky Performance Status (KPS) \>70
* English fluency
* physician approval
* willingness to travel to Halifax to participate.

Exclusion Criteria:

* unstable or symptomatic cardiac or pulmonary disease, injury or co-morbid disease that precludes ability to safely exercise
* significant cognitive limitations
* uncontrolled seizures associated with impaired awareness

Primary outcomes:
measure: Functional Performance
timeFrame: Baseline to post-intervention (12-week) change
measure: Grip strength
timeFrame: Baseline to post-intervention (12-week) change
Secondary outcomes:
measure: Body Mass Index (BMI)
timeFrame: Baseline to post-intervention (12-week) change
measure: Body composition and Muscle Mass
timeFrame: Baseline to post-intervention (12-week) change
measure: Muscle Mass
timeFrame: Baseline to post-intervention (12-week) change
measure: Aerobic fitness
timeFrame: Baseline to post-intervention (12-week) change
measure: Physical activity
timeFrame: Baseline to post-intervention (12-week) change
measure: Physical, functional, emotional, and social/family quality of Life
timeFrame: Baseline to post-intervention (12-week) change
measure: Fatigue
timeFrame: Baseline to post-intervention (12-week) change
measure: Cognitive functioning 1
timeFrame: Baseline to post-intervention (12-week) change
measure: Cognitive functioning 2
timeFrame: Baseline to post-intervention (12-week) change
measure: General Health (EuroQol) 5 Dimension - 5 Level
timeFrame: Baseline to post-intervention (12-week) change
measure: General Health (EuroQol) Visual Analog Scale
timeFrame: Baseline to post-intervention (12-week) change
Other outcomes:
measure: Study Feasibility - Participant Accrual
timeFrame: Captured over the 12-week study period
measure: Study Feasibility - Participant Attrition
timeFrame: Captured over the 12-week study period
measure: Study Feasibility - Participant Adherence
timeFrame: Captured over the 12-week study period
measure: Study safety
timeFrame: Captured over the 12-week study period
Locations:
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: Dahousie University and Nova Scotia Health Authority
name: Scott Grandy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nova Scotia Health Authority
name: Mary MacNeil, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Keats MR, Grandy SA, Blanchard C, Fowles JR, Neyedli HF, Weeks AC, MacNeil MV. The Impact of Resistance Exercise on Muscle Mass in Glioblastoma in Survivors (RESIST): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2022 May 4;11(5):e37709. doi: 10.2196/37709.