The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors

Study Overview
=================
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.

Official Title
-----------------
The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors (RESIST)

Conditions
-----------------
Glioblastoma Multiforme of Brain, Brain Cancer

Intervention / Treatment
-----------------
* Behavioral: Circuit-based resistance exercise (CRT)


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: RCTwith 1:1 allocation to intervention or wait-list control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Intervention<br>12-week circuit-based resistance exercise | Behavioral: Circuit-based resistance exercise (CRT)<br>* CRT is a common training method used to foster aerobic fitness, muscular endurance and strength, as well as neuromuscular adaptations in one workout. CRT is comprised of several sets of different exercises with little rest in between each set.<br>|
| No Intervention: Wait-list Control<br>Standard of care wait-list control group | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Performance | Short Physical Performance Battery to assess activities of daily living | Baseline to post-intervention (12-week) change | 
| Grip strength | Measured by handheld dynamometer | Baseline to post-intervention (12-week) change | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) | Weight (kg) and height (m) will be used to calculate BMI | Baseline to post-intervention (12-week) change | 
| Body composition and Muscle Mass | Arm, waist, and calf circumference (cm) | Baseline to post-intervention (12-week) change | 
| Muscle Mass | Muscle mass and quality - 3T diagnostic magnetic resonance imaging | Baseline to post-intervention (12-week) change | 
| Aerobic fitness | 6 minute walk will be used to calculate aerobic fitness | Baseline to post-intervention (12-week) change | 
| Physical activity | Godin Leisure Time Physical Activity Questionnaire - Leisure Score Index will be used to calculate self-reported leisure physical activity | Baseline to post-intervention (12-week) change | 
| Physical, functional, emotional, and social/family quality of Life | Functional Assessment of Cancer Therapy - Brain (FACT-Br) - 50 item scale; total scale score range 0-200; higher scores indicate higher overall QOL | Baseline to post-intervention (12-week) change | 
| Fatigue | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) - 13 item scale; score range 0-52; higher scores indicate less fatigue | Baseline to post-intervention (12-week) change | 
| Cognitive functioning 1 | Trail making test-b; Time taken to complete each task and number of errors made during each task are recorded and compared with normative data. Time to complete the task is recorded in seconds; the greater the number of seconds to complete the task, the greater the impairment. | Baseline to post-intervention (12-week) change | 
| Cognitive functioning 2 | Hopkins Verbal Learning Test-Revised for memory; total recall and recognition scores will be calculated | Baseline to post-intervention (12-week) change | 
| General Health (EuroQol) 5 Dimension - 5 Level | Mobility, self-care, usual activities, pain/discomfort, anxiety/depression (EuroQol-5Dimension-5Level; EQ-5D-5L) - 5 dimensions; higher scores indicate higher problems | Baseline to post-intervention (12-week) change | 
| General Health (EuroQol) Visual Analog Scale | EuroQol Visual Analog Scale 0-100; lower scores indicate worse health | Baseline to post-intervention (12-week) change | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise, Circuit-based resistance training, Intervention, Myopathy, Functional status, Quality of life, Randomized controlled trial