The SaVe Project-Sarcopenia and Vertigo in Aging Patients With Colorectal Cancer (SaVe)

The goal of this clinical trial is to learn about the cause of dizziness and decline in walking ability in in older adults ≥65 years during chemotherapy treatment for colorectal cancer. Another goal is to investigate if a comprehensive geriatric assessment and three months' specialized physical group-based exercise three times/week can counteract muscle weakness, vertigo, instability, impaired walking balance, and neuropathy

Study Overview

• Status: Recruiting
• Conditions: Cancer; Colorectal Cancer; Chemotherapy; Exercise; Sarcopenia; Vertigo; Rehabilitation; Elderly; Older Adults; Resistance Training; Geriatric; Chemotherapy-induced Peripheral Neuropathy; Vestibular Rehabilitation; Oncologic Complications; Comprehensive Geriatric Assessment; Frail; Postural Stability; Balance Training; Geriatric Oncology; Pragmatic Trial; Personal Medicine; Individualised
• Intervention / Treatment: Other: Targeted specialized physical group-based exercise and Comprehensive Geriatric Assessement

Detailed Description

Frequent adverse effects of chemotherapy in older adults are nausea and fatigue, but our research group have discovered a problem with many also suffering from sarcopenia, vertigo, dizziness, and peripheral neuropathy (CIPN) leading to balance and walking impairments causing increased risk of falls. Moreover, these symptoms are often underreported with inadequate awareness among health professionals leading to deficient focus on the need for targeted rehabilitation. A comprehensive geriatric assessment (CGA) can increase the number of frail, older patients completing chemotherapy and CGA-based interventions can decrease chemotherapy toxicity and improve health-related quality of life (HRQoL). Physical exercise has been shown to reduce muscle weakness, vertigo, dizziness, and impaired balance among older adults requiring limited resources. Therefore, this project aims to investigate the effectiveness of CGA and physical exercise to counteract muscle weakness, vertigo, instability, and impaired walking balance, during chemotherapy and to investigate the interaction between vertigo, postural stability and walking performance, and neuropathy and the prevalence of sarcopenia. The activities of specialized physical exercise planned in this intervention will, as hypothesized, result in a change in muscle strength, walking balance, self-perceived balance disabilities/dizziness, and fear of falling along with changes in peripheral nerve function and autonomic function and severity of CIPN which are the outcomes of this study. Accordingly, expectations are that this intervention will affect the HRQoL among older cancer patients with vertigo and walking impairments and reduce the number of falls and hospital admissions leading to a socioeconomic benefit.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Christensen, PhD; Email: jan.christensen.02@regionh.dk
• Study Contact Backup: Name: Katrine S Piper, PhD-Student; Phone Number: +4551156140; Email: katrine.storm.piper@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Not yet recruiting
    • Copenhagen University Hospital - Rigshospitalet
    • Contact: Jan Christensen, PhD; Phone Number: 38633092; Email: jan.christensen.02@regionh.dk
    • Principal Investigator: Katrine S Piper, PhD-Student
  • Herlev, Denmark, 2730
    • Recruiting
    • Copenhagen University Hospital - Herlev and Gentofte Hospital
    • Principal Investigator: Katrine S Piper, PhD-Student
    • Contact: Cecilia M Lund, PhD; Phone Number: +4538686112; Email: Cecilia.Margareta.Lund.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet the criteria of the oncological departments of receiving neoadjuvant, adjuvant or first line palliative chemotherapy for colorectal cancer
• ≥65 years of age at the time of signing the informed consent form
• Able to speak and read Danish, and to provide a signed informed consent form
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2

Exclusion Criteria:

• Chemotherapy treatment within two years and sequelae of neuropathy, or symptoms of dizziness or vertigo, or balance disturbance
• Severe physical disability that hinders physical exercise
• Dementia, psychotic disorders, or other cognitive diseases or conditions that hinder participation in a clinical exercise-based trial
• Inability to sign informed content
• Patients who have had a consultation in the geriatric outpatient clinic within the past six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Patients in the intervention groups will receive neoadjuvant, adjuvant or first line palliative chemotherapy (for metastatic disease). In addition, all patients will undergo three months' targeted specialized physical group-based exercise and Comprehensive Geriatric Assessment with corresponding interventions	Other: Targeted specialized physical group-based exercise and Comprehensive Geriatric Assessement; Vestibular rehabilitation, balance- and progressive resistance training for three months' three times/week and Comprehensive Geriatric Assessement including corresponding interventions
No Intervention: Usual care group; Patients in the usual care groups will receive standard treatment with neoadjuvant, adjuvant or first line palliative chemotherapy (for metastatic disease). If the patients have other health complaints, these will, as current standard procedure, be treated by oncologist or by referral to general practitioner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamic Gait Index (DGI)	Between-group difference in change in walking balance assessed with Dynamic Gait Index (DGI) scored on a 0-24 point total scale. Higher score means better outcome	Three months
30 second Sit-to-Stand Test (30STS)	Between-group difference in lower limb muscle strength and endurance	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital contacts due to falls	Hospital contacts due to falls	Baseline, three and six months
Autonomic function	Changes in autonomic function using Vagus device	Baseline, three and six months
Body composition	Changes in body composition using DXA	Baseline, three and six months
Falls	Self-reported falls	Baseline, two, four, six, eight, ten, twelve, fourteen, sixteen, eighteen, twenty, twenty-two, and twenty-four weeks
Balance disabilities/dizziness	Changes in self-perceived balance disabilities/dizziness using the patient reported outcome measure Dizziness Handicap Inventory (DHI) scored on a 0-100 point total scale. Higher score means worse outcome	Baseline, three and six months
Fear of falling	Changes in fear of falling using the patient reported outcome measure Short Falls Efficacy Scale International (Short FES-I) scored on a 0-28 point total scale. Higher score means worse outcome	Baseline, three and six months
Health related quality of life	Changes in health related quality of life using the patient reported outcome measure EORTC QLQ-C30. The total score is converted to a 0-100 scale. Higher score means better outcome	Baseline, three and six months
Peripheral nerve function	Changes in peripheral nerve function using biothesiometer mesured in 0-50 volts. Higher volts means worse outcome	Baseline, three and six months
Chemotherapy induced peripheral neuropathy	Severity of chemotherapy induced peripheral neuropathy using the patient reported outcome measure EORTC QLQ-CIPN-20. The total score is converted to a 0-100 scale. Higher score means worse outcome	Baseline, three and six months
Muscle strength	Changes in muscle strength using HUR Leg Press Rehab performance recorder measuring weight in kilograms	Baseline, three and six months
Muscle strength	Changes in muscle strength using handgrip test measuring weight in kilograms	Baseline, three and six months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postural control	Changes in postural control (standing balance) using HUR SmartBalance platform	Baseline, three and six months
Vestibular function	Changes in peripheral vestibular function using Video Head Impulse Test (vHIT)	Baseline, three and six months
Orthostatic blood pressure	Changes in orthostatic blood pressure measured from lying to standing and every minute for five minutes	Baseline, three and six months
Muscle quality	Changes in muscle quality using ultrasound	Baseline and three months
Activity level	Description of activity level using activity tracker	Baseline and three months
Cessation of chemotherapy	Description of cessation of chemotherapy	After 6, 12, and 24 weeks (from baseline)
Overall survival	Recording of overall survival	Follow-up at 1, 2, 3, and 5 years
Hospitalisations	Recording of hospitalisations	Follow-up at 1, 2, 3, and 5 years
Progression of cancer	Recording of progression of cancer	Follow-up at 1, 2, 3, and 5 years
Recurrence of cancer	Recording of recurrence of cancer	Follow-up at 1, 2, 3, and 5 years
Walking speed	Changes in walking speed using 10 meter walk test measuring gaitspeed in meters per second	Baseline, three and six months
Body composition	Changes in body composition using bioimpedance (BIA)	Baseline, three and six months
Frailty	Presence of frailty using Geriatric-8 (G8) scored on a 0-17 point scale. Higher score means better outcome	Baseline
Frailty	Presence of frailty using Clinical Frailty Scale (CFS) scored on a 1-9 point scale. Higher score means worse outcome	Baseline
Prescribed rehabilitation plan	Recording of exercise through a prescribed rehabilitation plan	Follow-up at 1, 2, 3, and 5 years
Biomarkers of sarcopenia and inflammation	Biomarkers of sarcopenia and inflammation collected through blood samples. To determine concentration of inflammatory cytokines; High-sensitivity C-reactive Protein (hsCRP), tumour necrosis factor alpha (TNF- α), interleukin 6 (IL6), interleukin 13 (IL-13), and of muscle atrophy and muscle wasting (growth differentiation factor 11 (GDF11), and growth differentiation factor 15 (GDF-15). Blood samples are analysed by standard ELISA-analyses for plasma samples.	Baseline, three and six months
Vision	Measurement of vision using a Snellen chart	Baseline

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Copenhagen University Hospital - Rigshospitalet, Department of Occupational Therapy and Physiotherapy; Copenhagen University Hospital - Herlev and Gentofte Hospital, Department of Medicine; Copenhagen University Hospital - Herlev and Gentofte Hospital, Department of Oncology; Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital; Odense University Hospital, Department of Geriatric Medicine; Copenhagen University Hospital - Amager and Hvidovre Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neuromuscular Diseases; Otorhinolaryngologic Diseases; Colonic Diseases; Intestinal Diseases; Neuromuscular Manifestations; Labyrinth Diseases; Ear Diseases; Pathological Conditions, Anatomical; Intestinal Neoplasms; Rectal Diseases; Muscular Atrophy; Atrophy; Vestibular Diseases; Sensation Disorders; Colorectal Neoplasms; Peripheral Nervous System Diseases; Sarcopenia; Vertigo; Dizziness
• Other Study ID Numbers: H-22064206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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