Pilot Prehabilitation Intervention in Lung Cancer

A Novel Multimodal Intervention for Surgical Prehabilitation of Patients With Lung Cancer: Pilot Study

Lung cancer is the second most prevalent cancer in Canada and the leading cause of cancer-related mortality worldwide. Patients diagnosed at earlier (non-metastatic) stages are potential candidates for surgical tumor removal. However, they often present with poor nutritional status and physical function adding to the major catabolic stress imposed by surgery that negatively impacts recovery and survival after surgery. The purpose of this study is to investigate the potential benefits of a prehabilitation program that includes a combined nutritional supplement (whey protein, leucine, vitamin D and omega-3 fatty acids) with exercise and relaxation techniques for 4 weeks before surgery and continued for 8 weeks after surgery on functional pre- and postoperative outcomes, versus standard hospital care (control). Investigators will study whether the prehabilitation program improves physical performance, muscle mass and quality of life in patients undergoing lung cancer resection. The specific objective of this pilot study is to test feasibility and adherence to intervention, and generate pilot data to inform the design of a larger trial.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Surgery
• Intervention / Treatment: Behavioral: Multimodal intervention (MM)

Detailed Description

RATIONALE: The preoperative period is an opportune time to actively engage and empower patients in improving their functional, nutritional and mental status in anticipation of the surgical stress. Considering that lung cancer patients often present with poor nutritional status and physical function prior to surgery providing a nutritional supplement to increase protein, leucine, vitamin D and omega-3 FA intake with a structured exercise program and relaxation techniques should improve muscle mass, strength and physical performance.

MAIN OBJECTIVE: to test the effect of a multimodal prehabilitation intervention (MM) combining a mixed-nutrient supplement with structured exercise training against standard of care (SOC), on functional pre- and postoperative outcomes in surgical patients with lung cancer, in an open-label RCT.

The present is a pilot study aiming to generate feasibility data (recruitment rate, compliance, attrition) and preliminary outcome data to support a larger trial.

STUDY DESIGN: Open-label, randomized, controlled trial of two parallel arms: multimodal intervention (MM) and standard of care (SOC). After baseline assessment, patients will be randomized to either group in a 1:2 SOC:MM ratio using a computer-generated randomization scheme by block of four, with stratification by sex and functional capacity (< or > 400 m on the 6MWT). Consecutive adult patients scheduled for elective video-assisted thoracic surgery or open thoracotomy surgery of NSCLC stages I, II or IIIa, will be approached following their first appointment with their surgeon at the MUHC-Montreal General Hospital.

INTERVENTION: The EXP arm will ingest a multi-nutrient supplement consisting of whey protein + leucine and fish oil + vitamin D, perform structured exercise and relaxation techniques for 4 weeks prior to surgery and 8 weeks after surgery. Control group will received standard hospital care and education on benefits of physical activity and healthy diet. Outcome assessment will be performed at baseline, preoperative, 4 and 8 weeks postoperatively.

OUTCOMES: Primary: feasibility; Secondary: physical function, muscle strength, volume and density, body composition, quality of life, length of stay and post-operative complications; Other: dietary intake, physical activity, clinical markers.

STATISTICAL ANALYSIS: This is a pilot study designed to generate data on feasibility and compliance to the intervention and study tests; it is not powered for identifying statistical differences in the main outcomes. The investigators will recruit 36 participants on a 1:2 ratio (12 SOC: 24 MM).

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Research Institute of the McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult men and women with NSCLC stages I, II or IIIa, planned for video-assisted thoracic surgery (VATS) or open thoracotomy surgery for cancer resection or exploration.

Exclusion Criteria:

• prior recent (<3 mo) chemotherapy, comorbidities contraindicating exercise (defined as CPET <10 mL O2/kg/min), walking aids other than a cane, glomerular filtration rate <30 mL/min/m2, allergy to milk or seafoods, chronic use of anti-coagulants, hypercalcemia, hypervitaminosis D, insufficient understanding of English or French language to provide informed consent. All medications and co-morbidities will be recorded. Patients taking vitamin D will continue their supplements; risk of potential overdosing will be monitored by serum 25(OH)D levels >80 nmol/L. Those taking n-3 FA supplements will be asked to withhold during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multimodal intervention (MM); Multimodal prehabilitation including structured exercise (1 supervised exercise session per week + home-based exercise program), nutritional optimization (diet + mixed nutrient supplement containing whey protein, leucine, vitamin D and omega 3 fatty acids) and relaxation strategies.	Behavioral: Multimodal intervention (MM); Exercise: Moderate intensity resistance and aerobic exercise, including one weekly supervised session and a home-based program. Participants were asked to 1) accumulate 30 min of aerobic exercise per day of their preferred type (ex. walking) and 2) perform 30 min of resistance exercise targeting major muscle groups, every second day for 2 sets of 8-12 reps. Nutrition: Optimize diet with protein-rich foods to meet protein intake of >1.2 g/kg/d and energy of 25-30 kcal/kg/d. The supplement consists of whey protein isolate (with the goal of reaching 1.5 g/kg/d, providing 25 g/meal), 6g of leucine, fruit-flavored fish oil added with vitamin D. Relaxation strategies: private consultations with psychology-trained personnel whereby techniques aimed at reducing anxiety are practiced. Participants are also provided with a compact disc with relaxation exercises to be used at home 2-3 times per week.
No Intervention: Standard of care (SOC); Education on benefits of physical activity and healthy diet, with no specific information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: Recruitment rate	Recruitment rate (measured in percent, compared to expected rates)	Over entire recruitment period (approximately 1 year)
Feasibility: Adherence to intervention	Adherence to exercise and nutritional interventions (measured in percent, compared to expected rates)	Over 12 weeks (4 weeks pre- and 8 weeks post-surgery)
Feasibility: completion of study outcome assessment	Completion of study outcome assessments (measured in percent, compared to expected rates)	Over 12 weeks (4 weeks pre- and 8 weeks post-surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional walking capacity	Six-minute walking test: measured as the distance walked during 6 minutes, along a 20-m corridor, expressed in m)	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Length of hospital stay	Recorded from medical charts	8-week postoperative
Post-operative complications	Recorded from medical charts and will be graded by severity following the Clavien-Dindo classification.	8-week postoperative
Health related quality of life	Measured by the cumulative score of the 36-item Short Form Health Survey, score 0-100, higher score means better quality of life.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Quality of Life	Measured by cumulative score of the Functional Assessment of Cancer Therapy - Lung questionnaires, score 0-136, higher means better quality of life.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Muscle strength - handgrip	Handgrip strength using hand-held Jamar dynamometer, measured in kg.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Muscle strength - leg	Isokinetic leg strength (knee extension peak torque) using Biodex, measured in N, on the dominant side.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Muscle volume	Skeletal muscle volume will be measured in the dominant foreleg, using peripheral quantitative CT (pQCT, Stratec XCT2000).	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Muscle radiodensity	Skeletal muscle density will be measured in the dominant foreleg, using peripheral quantitative CT (pQCT, Stratec XCT2000).	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Body composition	Lean and fat mass will be measured by bioelectrical impedance (InBody 230V)	Baseline, preoperative, 4-week postoperative and 8-week postoperative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary assessment	Collected using 2 and 3-day food diaries.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Plasma phospholipid n-3 FA profile	Plasma lipids will be extracted with organic solvents, phospholipids isolated on thin-layer chromatography, and FAs methylated for determination by gas chromatography-flame-ionization analysis. Used as an objective measure of adherence to fish oil.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Serum 25(OH)D	Concentrations will be measured by the MUHC-Central Lab. Used as an objective measure of adherence to the supplement.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Inflammation	Will be assessed with serum C-reactive protein (hs-CRP) by MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Serum albumin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Pre-albumin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Hemoglobin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Exercise tolerance - oxygen consumption	Assessed using cardiopulmonary exercise testing and measuring oxygen consumption at anaerobic threshold and peak exercise	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Exercise tolerance - workload	Assessed by cardiopulmonary exercise testing at anaerobic threshold and peak exercise	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Exercise tolerance - heart rate	Assessed by cardiopulmonary exercise testing and measured at anaerobic threshold and peak exercise	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Pulmonary function (FEV1)	Spirometry standard methods to measure FEV1.	Baseline and 4-week postoperative
Pulmonary function (FVC)	Spirometry standard methods to measure FVC.	Baseline and 4-week postoperative
Pulmonary function (FEV1/FVC)	Spirometry standard methods to measure the FEV1/FVC ratio.	Baseline and 4-week postoperative
Pulmonary function (FEF 25-75%)	Spirometry standard methods to measure FEF 25-75 percent.	Baseline and 4-week postoperative
Physical activity	Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire, score 0 - x (no maximum score), higher mean more activity	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Anxiety/depression	Hospital Anxiety and Depression Scale (questionnaire). Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Nutritional status	Patient-Generated Subjective Global Assessment (PG-SGA). In general, the higher total additive scores upon initial exam correlates with more severely malnourished cases (A = well nourished, B = moderately malnourished or suspected malnutrition and C = severely malnourished).	Baseline, preoperative, 4-week postoperative and 8-week postoperative

Collaborators and Investigators

• Sponsor: McGill University
• Collaborators: Peri-Operative Program Charitable Foundation; MUHC-Montreal General Hospital Foundation

Publications and helpful links

General Publications

• Lawson C, Ferreira V, Carli F, Chevalier S. Effects of multimodal prehabilitation on muscle size, myosteatosis, and dietary intake of surgical patients with lung cancer - a randomized feasibility study. Appl Physiol Nutr Metab. 2021 Nov;46(11):1407-1416. doi: 10.1139/apnm-2021-0249. Epub 2021 Jul 15.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2019
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 29, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Prehabilitation; Nutritional supplement
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: MUHC REB 2020-5633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD sharing was not planned originally and therefore consent was not obtained for it.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No