Combined Exercise and Cognitive Stimulation for Falls Prevention

Study Overview
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Brief Summary
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Randomized clinical trial of 310 older adults over 75 years old recruited from the Falls Units of Geriatric Departments in 4 three University Hospitals in Spain (Pamplona, San Sebastián, Albacete and Barcelona). Participants who met inclusion criteria will be randomized to the usual care group (Otago exercise program) or the Vivifrail-Cog Intervention (a combination of physical exercise Vivifrail program and cognitive training). The main objective of the present randomized clinical trial is to investigate the effect of the combined intervention (exercise and cognitive intervention) in frail older participants living in the community and at risk of falling. The main endpoint will be the rate of falling in the following year. Secondary endpoints include physical performance, muscle strength, cognitive performance, hospitalizations, institutionalization, depression and quality of life.

Detailed Description
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Usual care: subjects randomized to the usual care group will receive an evidence-based multidisciplinary intervention tailored at reducing the fall risk (polypharmacy, environmental intervention, physical exercise). Importantly, the Otago exercise program (considered the standard physical exercise intervention) will be prescribed in this group. Intervention group: subjects assigned to this intervention will engage in a multicomponent intervention combining an exercise program, Vivifrail (A practical guide for prescribing a Multicomponent Physical Training Program to prevent weakness and falls in people over 70, more information at www.vivifrail.com) and a cognitive training. Vivifrail exercise program combines resistance, endurance, balance and flexibility exercise tailored to the functional level of the subjects, guaranteeing an individualized approach. Exercises progress in terms of intensity and difficulty as the subject adapts to exercise. The cognitive stimulation program combines exercises to work on different cognitive functions, mainly addressing executive functions (attentional system, processing speed, perceptual organization, working memory and cognitive flexibility, verbal comprehension, abstraction and reasoning, planning, execution and problem solving ). It lasts 12 weeks, two weekly sessions. It is divided into 4 levels in order to adapt the intervention to participant's individual capacity, and the level can be adjusted throughout the intervention. Correct execution will be monitored by constant contact with relatives in charge of supervising the exercise program, who will be familiarized with the intervention prior to participation.

Official Title
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Effect of an Individualized Combined Intervention (Vivifrail-Cogn) on the Rate of Falling of Frail Older Adults at Risk of Falling Living in the Community: a Multicenter Randomized Clinical Trial.

Conditions
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Fall, Frailty, Cognition Disorders in Old Age, Exercise, Cognitive Change

Intervention / Treatment
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* Other: Vivfrail-Cog combined multicomponent physical exercise and cognitive stimulation.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 75 years or older Referral to the Falls Unit Ability to ambulate independently with or without technical aids Barthel Index ≥ 60 Pre-frailty (1-2 criteria) or Frailty according to the Frailty Phenotype by Fried et al Risk of falling according to following criteria: Gait disorders captured through physical performance measures (Time Up and Go Test ≥ 20 s and/or Gait Speed ≥0,8 m/s ≥2 self-reported falls in the previous year ≥1 self-reported falls requiring medical assistance Relative/caregiver willingness to supervise the exercise/cognitive stimulation sessions Capability and willingness to provide informed consent Exclusion Criteria: Unwillingness to either complete the study requirements or to be randomized into the control or the intervention group Life expectancy ≤ 3 months Terminal illness No possibility of follow-up Institutionalization or awaiting institutionalization Major cognitive impairment DSM-V moderate or severe (CDR 2-3 /GDS 5-7) No ability to read and write Severe visual and hearing deficit Any contraindications for physical exercise or testing procedures, including but not limited to: myocardial infarction in the past 3 months unstable angina pectoris uncontrolled arrhythmia unstable cardiovascular disease or other unstable medical condition uncontrolled arterial hypertension recent pulmonary thromboembolism upper or lower extremity fracture in the past 3 months

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined multicomponent physical exercise and cognitive stimulation (Vivfrail-Cog)<br>The supervised multicomponent exercise training program (resistance, endurance, balance and flexibility) will be comprised of upper and lower body exercises tailored to the individual's functional capacity. Subjects will be encouraged at performing strength and endurance exercise at a moderate intensity. Exercise will progress in terms of intensity and difficulty upon individual adaptation. The cognitive intervention will include the performance of different exercises with pencil and paper in order to train different cognitive areas, especially the executive functions. | Other: Vivfrail-Cog combined multicomponent physical exercise and cognitive stimulation.<br>* The areas to be worked on are: Attentional system: selective attention and concentration; alternating attention / dual attention; Processing speed; perceptual organization; working memory and cognitive flexibility; comprehension, abstraction and verbal reasoning, planning, execution, and problem solving. Four programs have been developed stimulation different difficulty levels to adapt to the capabilities of each participant.<br>|
| No Intervention: Usual care<br>The usual care group will receive normal outpatient care (including the evidence-based Otago exercise program). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year falls rate | Fall: an unexpected event in which the participants come to rest on the ground, floor, or lower level.Subjects will be contacted by phone in a monthly basis after completing the 3-months lasting intervention and inform the research team about the incidence of falls. | during one year | 
| One year fall-related hospitalizations | Number of fall-related hospitalizations | during one year | 
| One year fall-related fracture | Number of fall-related fracture (radiologically confirmed) | during one year | 
| One year fall-related death | Number of fall-related death | during one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barthel | Barthel Index changes from baseline to 6-week, 12-week and 24-week and 1-year | At baseline, 6-week, 12-week and 24-week and 1-year. | 
| Garvan Fracture Risk | Changes from baseline to 12-week The Fracture Risk Calculator was developed using data collected in the internationally renowned Dubbo Osteoporosis Epidemiology Study conducted by the Bone and Mineral Research Program of Sydney's Garvan Institute of Medical Research. It estimates the 5-year and 10-year risk of hip and any fracture based on information on sex, age, number of fractures since the age of 50, the rate of falling and the bone mineral density. | At baseline and 12-week | 
| Handgrip Strength in both hands | Changes from baseline to 6-week and 12-week.Handgrip strength will be measured by using a dynamometer (JAMAR) in both dominant and non-dominant hand. Best performance of two trials will be registered. | At baseline, 6-week, 12-week | 
| 4-metre gait velocity test (GVT) | Changes from baseline to 6 week and 3 months.Gait ability will be assessed using the 6-metre gait velocity test (GVT). Starting and ending limits will be marked on the floor with tapelines for a total distance of 8 meters. Participants will be instructed to walk in their self-selected usual pace for two attempts. The best result of both trials will be registered. The first and last metre, considered the warm-up and deceleration phases, respectively, will not be included in calculations of the gait assessment. Higher scores ( > 1.0 m/s) indicates better functional capacity and lower scores (< 0.8 m/s) scores worse functional capacity. | At baseline, 6 week and 3 months. | 
| Short Physical Performance Battery (SPPB) | Changes from baseline to 1 and 3 months. The functional capacity of patients will be evaluated by the Short Physical Performance Battery (SPPB) which evaluates, balance, gait ability, and leg strength using a single tool. The total score ranges from 0 (worst) to 12 points (best). The SPPB test has been shown to be a valid instrument for screening frailty and predicting disability, institutionalization, and mortality. A total score of less than 10 indicates frailty and a high risk of disability and falls. A one-point change in the score has clinical relevance | At baseline,1 and 3 months. | 
| Fried's Frailty Phenotype (FP) | Changes from baseline to 3 months. The Fried's Frailty Phenotype (FP) consists of five items: weight loss, exhaustion, strength, physical activity and gait speed. For grip strength, 3-m GS and Physical Activity Scale for the Elderly (PASE) scores. Subjects are classified as robust if not meeting any criteria, pre-frail if they met 1-2 of the criteria and frail if ≥3 were present. | At baseline and 3 months | 
| SARC-F (Screening of Sarcopenia Among Older Adults) | Changes from baseline to 1 and 3 months. The SARC-F is a screening scale to ascertain the risk of sarcopenia (the presence of age-associated low muscle mass and function). It is composed of 5 items related to the presence of difficulty in loading weights, walking, standing-up from a chair, climbing stairs and the number of falls in the previous year. A score greater than 4 is indicative of the presence of sarcopenia. | At baseline,1 and 3 months. | 
| Musculoskeletal echography | Changes from baseline to 6-week and 3 months. Muscle thickness and quality will be assessed through musculoskeletal echography, a non-intrusive imaging method. Muscle thickness and quality (infiltration of non-contractile tissue) will be measured in the rectus femoris (region from sub-cutaneous tissue to the bone surface). | At baseline, 6 weeks and 3 months | 
| MOCA (Montreal Cognitive Assessment) test | Changes from baseline to 6-week and 3 months. cognitive function will be measured with MOCA ( Montreal Cognitive Assessment Test) in case of mild cognitive decline. The MOCA is a validated test in Spanish It ranges from 0 ( worse score ) to 30 (best score). A score less than 26 indicates suggest mild cognitive decline | At baseline, 6 weeks and 3 months | 
| Trail Making Test part A ( TMT-A) | Changes from baseline to 6-week and 3 months. Executive function will be assessed with the Trail Making Test part A. Results for TMT A are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.Average will be consider 29 seconds, Deficient > 78 seconds and Rule of Thumb most 90 seconds | At baseline, 6 weeks and 3 months | 
| Falls-related psychological consequences | Changes from baseline, 12-week visit; and 24-week and 1-year. Fear of falling will be evaluated through three questions: ''Are you afraid of falling?'', ''Do you limit any house-hold activities because you are frightened you may fall?'', ''Do you limit any outside activities because you are frightened you may fall?''. FES-I was developed as part of the Prevention of Falls Network Europe (ProFaNE) project from 2003 to 2006, following an intensive review of fear of falling, self-efficacy and balance confidence questionnaires. It ascertains the impact that fear of falling has on 16 activities of daily living. Scores range from 16 to 64 and classify the fear of falling as low (16-19), moderate (20-27) and high (28-64) concern. | At baseline, 12 week, 24 week and 1 year. | 
| 1-Repetition Maximum (RM) Maximal dynamic strength test | Changes from baseline to 6-week and 3 months. Maximal dynamic strength will be assessed using the 1Repetition Maximum (RM) test in the bilateral leg press exercise using exercise machines (Exercycle, S.L., BH Group, Vitoria, Spain). In the first assessment, the subjects will warm up with specific movements for the exercise test. Each subject's maximal load will be determined in no more than five attempts, with a 3-min recovery period between attempts | At baseline, 6 weeks and 3 months | 
| Repetitions at maximal velocity at intensities of 50% of 1RM test | Changes from baseline to 6-week and 3 months. Participants will perform ten repetitions at maximal velocity at intensities of 50% of 1RM to determine the maximum power (w) and the loss of power during the ten repetitions in the leg press exercise. Higher values indicate better functional capacity | At baseline, 6 weeks and 3 months | 
| Geriatric Depression Scale (GDS) Yesavage abbreviated scale | Changes from baseline to 6-week and 3 months. Depression will be assessed wit the GDS Yesavage abbreviated scale of 15 items. Is is ranged between 0 ( best value) to 15 ( worse value). Scores between 0-5 indicates normality, 5-9 minor depression and scores over 9 indicates mayor depression | At baseline, 6 weeks and 3 months | 
| Mortality | Mortality will be assessed with a clinical questionnaire during follow up | At baseline, 6 weeks and 3 months | 
| Admissions to the hospital | New admissions to the hospital will be assessed with a clinical questionnaire during follow up | At baseline, 6 weeks and 3 months | 
| Incidence of institutionalization to nursing homes | New institutionalizations to nursing homes will be assessed with clinical questionary during follow up | At baseline, 6 weeks and 3 months | 
| Visit to emergency room | Visits to emergency room will be assessed with a clinical questionnaire during follow up | At baseline, 6 weeks and 3 months | 
| Number of total Drugs | Number of drugs during follow up will be assessed with a clinical questionnaire | At baseline and 3 months | 
| Presence of 5 or more drugs ( Polypharmacy ) registration | Registration of the presence of 5 or more drugs( Polypharmacy ) during follow -up will be done with a clinical questionnaire | At baseline and 3 months | 
| Psychotropic and hypotensive drugs registration | Registration of the presence of psychotropic and hypotensive drugs during follow -up will be done with a clinical questionnaire | At baseline and 3 months | 
| Drug Burden Index | It is a pharmacological measure of an individual's exposure to medications with anticholinergic and sedative effects. DBI is calculated for an individual by summing the burdens from every anticholinergic or sedative medicine they take regularly. A calculator available in https://www.anticholinergicscales.es/ will be used. | At baseline, 3, 6, 9 and 12 months | 
| Dual task gait ( arithmetic) 6 m velocity test | The dual-task paradigm will be used in the 6-m habitual GVT. Two trials will be conducted (best record will be taking in account) During the arithmetic dual-task condition (arithmetic GVT), we will assess gait velocity while participants are counting backward aloud from 100 by ones | At baseline, week 6 and 3 months | 
| Dual task gait (verbal) 6 m velocity test | The dual-task paradigm will be used in the 6-m habitual GVT. Two trials will be conducted(best record will be taking in account)During the verbal dual-task condition (verbal GVT), we will assess gait velocity while participants are naming animals by loud | At baseline, 6-week and 3 months | 
| EuroQol-5D (EQ-5D) Quality of life assessment test | Quality of life will be assessed with an international validated scale EuroQol-5D (EQ-5D). Its composed by. It asses health status (mobility, personal care, basic and instrumental daily living activities , pain and ansiety/depression) ranged from 0 ( worst health status) to 100 ( best health status ) | At baseline and 3 months | 
| - Registration of other geriatric syndromes (visual and hear impairment, urinary and fecal incontinence, delirium , dysphagia, constipation , pressure ulcers ) | Presence of other geriatric syndromes ( visual and hear impairment, urinary and fecal incontinence, delirium , dysphagia, constipation , pressure ulcers ) will be assessed with a clinical questionnaire | At baseline and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fall, Frailty, Cognition Disorders in Old Age, Exercise, Cognitive Change