Pilot Prehabilitation Intervention in Lung Cancer

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04610606
• Other study ID #: MUHC REB 2020-5633
• Status: Terminated
• Phase: N/A
• Start date: October 11, 2019
• Est. completion date: March 12, 2020

Study information

• Verified date: October 2020
• Source: McGill University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: March 12, 2020
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Surgery

Intervention

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.

Locations

Country	Name	City	State
Canada	Research Institute of the McGill University Health Centre	Montréal	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
McGill University	MUHC-Montreal General Hospital Foundation, Peri-Operative Program Charitable Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dietary assessment	Collected using 2 and 3-day food diaries.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	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
Other	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
Other	Inflammation	Will be assessed with serum C-reactive protein (hs-CRP) by MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	Serum albumin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	Pre-albumin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	Hemoglobin	Will be analyzed as standard procedures by the MUHC-Central Lab.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	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
Other	Exercise tolerance - workload	Assessed by cardiopulmonary exercise testing at anaerobic threshold and peak exercise	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Other	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
Other	Pulmonary function (FEV1)	Spirometry standard methods to measure FEV1.	Baseline and 4-week postoperative
Other	Pulmonary function (FVC)	Spirometry standard methods to measure FVC.	Baseline and 4-week postoperative
Other	Pulmonary function (FEV1/FVC)	Spirometry standard methods to measure the FEV1/FVC ratio.	Baseline and 4-week postoperative
Other	Pulmonary function (FEF 25-75%)	Spirometry standard methods to measure FEF 25-75 percent.	Baseline and 4-week postoperative
Other	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
Other	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
Other	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
Primary	Feasibility: Recruitment rate	Recruitment rate (measured in percent, compared to expected rates)	Over entire recruitment period (approximately 1 year)
Primary	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)
Primary	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	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
Secondary	Length of hospital stay	Recorded from medical charts	8-week postoperative
Secondary	Post-operative complications	Recorded from medical charts and will be graded by severity following the Clavien-Dindo classification.	8-week postoperative
Secondary	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
Secondary	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
Secondary	Muscle strength - handgrip	Handgrip strength using hand-held Jamar dynamometer, measured in kg.	Baseline, preoperative, 4-week postoperative and 8-week postoperative
Secondary	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
Secondary	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
Secondary	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
Secondary	Body composition	Lean and fat mass will be measured by bioelectrical impedance (InBody 230V)	Baseline, preoperative, 4-week postoperative and 8-week postoperative