Clinical trial NCT05955248: Multimodal Prehabilitation for Lung Cancer Surgery
Official title: A Novel Multimodal Intervention for Surgical Prehabilitation of Patients With Lung Cancer: the MMP-LUNG Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Cancer
Surgery
Keywords: Prehabilitation
Nutritional Supplement
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2023-07-21
Enrollment: 168
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial, 3 parallel arms (multimodal intervention, MM; nutritional supplement, NUT; control, CTRL), double-blind and placebo-controlled for supplement, single centre.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The main objective of this randomized controlled trial (RCT) is to investigate whether a multimodal prehabilitation intervention combining a mixed-nutrient supplement with structured exercise training (MM) or the supplement alone (NUT), against a placebo (CTRL), leads to improvement in functional capacity and postoperative outcomes in surgical patients with lung cancer, at nutritional risk. This will be tested in a single centre RCT of 3 parallel arms, double-blinded for the supplement. Female and male participants (n=168, \>=45 y) will be randomized to a 10-week intervention spanning 4 weeks pre-surgery and 6 weeks post-hospital discharge. The primary outcome is functional capacity as measured by the 6-minute walk test. Secondary outcomes include muscle mass, quality and strength, quality of life, length of hospital stay, and postoperative complications.

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 fatty acid 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 RCT prehabilitation intervention (MM) combining a mixed-nutrient supplement with structured exercise training or the supplement alone (NUT) against a placebo (CTRL), on functional pre- and postoperative outcomes in surgical patients with lung cancer at nutritional risk.

STUDY DESIGN: 10-week randomized controlled trial of 3 parallel arms, double-blinded for supplement: control (CTRL), multi-nutrient supplement (NUT) and multimodal intervention (MM). After baseline assessment, patients will be randomized to either group in a 1:1:1 CTRL:NUT:MM ratio using a computer-generated randomization scheme by permuted block sizes, with stratification by sex and functional capacity (\< or \> 450 m on the 6-minute walk test (6MWT). Consecutive adult patients = or \> 45 years scheduled for elective video-assisted thoracic surgery or open thoracotomy surgery of non-small cell lung cancer (NSCLC) stages I, II or IIIa and a Patient-Generated Subjective Global Assessment (PG-SGA) score = or \> 3, will be approached following their first appointment with their surgeon at the McGill University Health Centre (MUHC)-Montreal General Hospital.

INTERVENTION: The NUT arm will ingest a multi-nutrient supplement consisting of whey protein + leucine + viatmin D, and fish oil. The CTRL participants will receive placebo supplements with the same physical aspect, flavor and packaging as the active supplement.The MM arm will receive the NUT intervention in addition to performing structured exercise and relaxation techniques for 4 weeks prior to surgery and 6 weeks after hospital discharge.

OUTCOMES: Primary: physical capacity measured by the 6MWT; Secondary: physical function, muscle strength, total skeletal muscle mass, leg muscle volume and density, body composition, quality of life, length of stay and post-operative complications; Other: dietary intake, physical activity, exercise tolerance, pulmonary function, clinical markers.

STATISTICAL ANALYSIS: Intention-to-treat analysis will be performed in the primary analyses. For preoperative data, analysis of covariance (ANCOVA) will compare between-group differences at 4-week preoperative time, conditioned for baseline data, including predefined covariates in the model (age, sex, BMI). The hypothesis of full recovery from the intervention at 6 weeks postoperative (i.e. 6MWT returning back to or exceeding baseline) will be tested by logistic regression (yes/no). Between-group changes in other outcomes will be evaluated as differences in mean or proportions, as appropriate, with 95% CIs.

Eligibility criteria: Inclusion Criteria:

* Adults aged 45 years and over
* Diagnosed with NSCLC stages I, II or IIIa and scheduled for video-assisted thoracic surgery (VATS) or open thoracotomy surgery for cancer resection
* At nutritional risk (defined as Patient Generated-Subjective Global Assessment score = or \>3)

Exclusion Criteria:

* Prior recent (\<2 months) adjuvant therapy (chemo- or radio-therapy)
* Inability to perform, or comorbidities contraindicating, exercise (defined as CPET \<10 mL O2/kg/min)
* Unable to walk (uses a wheelchair)
* Allergy to milk or seafood
* Hypercalcemia (total serum Ca \>2.60 mmol/L or ionized Ca \>1.30 mmol/L)
* Hypervitaminosis D (serum 25(OH)D \>375 nmol/L)
* Glomerular filtration rate (\<30 mL/min/1.73m2)
* Insufficient understanding of English or French to provide informed consent

Patients taking omega-3 FA supplements will be asked to withhold them during the study; those taking vitamin D will continue unless baseline serum 25(OH)D \>80 nmol/L.

Primary outcomes:
measure: Change in preoperative functional walking capacity
timeFrame: From baseline (4 weeks pre-surgery) to surgery
measure: Postoperative functional walking capacity
timeFrame: 6 weeks after surgery
Secondary outcomes:
measure: Change in handgrip strength
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in total skeletal muscle mass
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in foreleg muscle surface area
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in foreleg myosteatosis (radiodensity)
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in body weight and composition
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in self-reported quality of life
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in self-reported functional assessment
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Length of hospital stay
timeFrame: 6 weeks after surgery
measure: Number and severity of postoperative complications
timeFrame: 6 weeks after surgery
Other outcomes:
measure: Change in dietary intake
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in plasma phospholipid fatty acid profile
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in serum vitamin D 25(OH)D concentrations
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in serum C-Reactive Protein (CRP)
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in serum albumin
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in serum pre-albumin
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in serum hemoglobin
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in complete blood count
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in preoperative exercise tolerance
timeFrame: From baseline (4 weeks pre-surgery) to surgery
measure: Change in forced expiratory volume (FEV1)
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in forced vital capacity (FVC)
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in self-reported physical activity level score
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in physical activity
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in anxiety/depression score
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Change in Patient-Generated Subjective Global Assessment (PG-SGA) score
timeFrame: From baseline (4 weeks pre-surgery) to 6 weeks after surgery
measure: Number of adverse events
timeFrame: Through study completion, an average of 10 weeks
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
affiliation: McGill University
name: Stéphanie Chevalier, PhD
role: PRINCIPAL_INVESTIGATOR
References: