Effects of VIVIFRAIL Program on Functional Capacity and Geriatric Syndromes in the Elderly (VIVIAL)

1. Theoretical Framework and Study Rationale

   Population aging poses a crucial challenge for healthcare systems. In Spain, a country with a high life expectancy of 83.8 years (exceeding the European average), ensuring active and healthy aging that preserves individual autonomy is a priority. The World Health Organization (WHO) promotes a paradigm shift focused on "intrinsic capacity" and "functional ability," moving away from the traditional disease-centered approach to prioritize the preservation of physical and mental functionality.

   Within this context, frailty stands out as a key, modifiable geriatric syndrome characterized by the age-related decline of multiple physiological systems, which increases vulnerability to adverse health outcomes such as falls, hospitalization, disability, and mortality. In Spain, frailty affects 18% of adults aged 65 and older and up to 38% of those aged 85 or older. Marked sociodemographic disparities exist: women present double the risk compared to men due to cumulative social and economic factors, and frailty is significantly more prevalent in lower socioeconomic and educational strata. Furthermore, its healthcare cost exceeds €2,500 per frail person annually.

   Multicomponent physical exercise (combining strength, endurance, balance, and gait training) is the most effective evidence-based strategy to prevent or reverse frailty. The Vivifrail program, internationally supported by scientific evidence, offers individualized, validated exercise protocols. However, most studies evaluating Vivifrail have been conducted in controlled clinical or hospital environments, leaving a gap in evidence regarding its real-world, home-based implementation prescribed from Primary Care in Spain. This study aims to validate the effectiveness of the Vivifrail program in Primary Care routine practice in Almería and evaluate the medium-term sustainability of functional gains after completing the supervised intervention.

2. Detailed Hypothesis and Objectives Main Hypothesis: Participation in the home-based Vivifrail multicomponent exercise program significantly improves functional capacity (measured via the Short Physical Performance Battery, SPPB) in pre-frail and frail older adults (aged >=70 years).

   Exploratory Hypothesis: Participants who maintain regular home physical exercise after completing the 12-week supervised intervention will exhibit greater persistence/sustainability of the functional benefits achieved during the program.

   Secondary Objectives:

   - To determine the program's effect on various geriatric syndromes and health conditions: chronic pain, appetite, fall risk, sarcopenia, mild cognitive impairment, sleep disturbances, depression, malnutrition, urinary incontinence, and frailty status.

   - To identify the clinical and sociodemographic profile of patients most likely to benefit from the intervention.

   • To evaluate the maintenance of functional and geriatric improvements 3 months after completing the 12-week intervention.
   • To assess the continuation of regular home physical exercise practice during the post-intervention follow-up period.
   • To record the occurrence of relevant clinical events during post-intervention follow-up (falls, fractures, emergency room visits, hospital admissions, institutionalization, and mortality).
   • To explore whether participants maintaining regular physical exercise show greater retention of functional improvements compared to non-maintainers.

3. Study Design and Setting

   This is a prospective, longitudinal, quasi-experimental, pretest-posttest, non-randomized, single-arm interventional study with a post-intervention observational follow-up phase. Participant recruitment, clinical assessments, and follow-up visits will be centralized within the Primary Care setting at the Virgen del Mar Health Center in Almería, Spain.

4. Sampling Strategy and Recruitment

   Participant selection will be performed using non-probabilistic consecutive quota sampling by sex to reflect the epidemiological higher prevalence of frailty in women (2:1 ratio). With a target sample size of 86 participants, stratified quotas are set at 66% women ($n=57$) and 34% men ($n=29$).

   Selection Criteria:

   - Inclusion Criteria: Age >=70 years; pre-frailty or frailty according to the FRAIL scale ($\ge 1$ point); Barthel Index >= 60 points; adequate communication ability; and ability to ambulate independently (with or without technical aids).

   - Exclusion Criteria: Recent acute myocardial infarction or unstable angina; uncontrolled cardiac arrhythmias; aortic dissection/severe stenosis; acute endocarditis/pericarditis; uncontrolled hypertension or severe orthostatic hypotension; acute thromboembolic disease; severe acute heart or respiratory failure; uncontrolled diabetes with severe hypoglycemia; recent bone fracture in the last month; or institutionalization.

   Recruitment Process:

   - Identification: Target population lists (age >=70 years) will be extracted from the Andalusian Health Service EMR system (Diraya).

   - Screening: Consecutive phone calls will be made to obtain verbal consent for initial screening using the FRAIL scale, Barthel Index, and EMR medical history review.

   - Consent & Enrollment: Eligible candidates will be scheduled for an in-person Baseline Visit to review and sign the Informed Consent document.

   - Bias Control: An anonymized database will track all contacted patients, recording reasons for refusal or withdrawal to evaluate potential selection bias.

5. Detailed Description of the Intervention The intervention consists of a 12-week, home-based, individualized, multicomponent physical exercise program prescribed and monitored by research physicians following the Vivifrail framework.

   - Passport Assignment: Functional baseline level determined via SPPB scores guides passport prescription: Type B (frailty, SPPB 4-6) or Type C (pre-frailty, SPPB 7-9). In patients identified as having a high risk of falls (TUG $> 20$ s, gait speed $< 0.8$ m/s, dementia, or history of medical/recurrent falls), Type B+ or C+ variants incorporating specialized balance and fall-prevention routines are assigned.

   - Session Structure: 5 sessions per week:

   * 3 Multicomponent Days (45-60 min): Warm-up, upper/lower limb resistance training (using water bottles, elastic bands, or stress balls), static/dynamic balance exercises, joint flexibility, and cool-down.

   * 2 Aerobic Endurance Days: Brisk walking for 20-40 minutes adapted to individual tolerance.

   • Progression and Intensity: Maintained at a moderate rate of perceived exertion (Borg Scale score 4-6). Systematic progression in duration/load is applied starting at week 7.
   • Post-Intervention Period: Following week 12, participants receive general health recommendations to autonomously continue regular exercise using their Vivifrail passport. No active intervention or research contact takes place during the post-intervention period until Visit 4.

6. Visit Schedule and Clinical Procedures

Fieldwork includes 4 in-person evaluation milestones at the Virgen del Mar Health Center:

1. Baseline Visit (V1 - Week 0): Signing of informed consent, comprehensive baseline assessment of all variables, Vivifrail passport prescription, delivery of materials (including the Activity Diary), standardized exercise demonstration, and safety training.
2. Intermediate Visit (V2 - Week 6): Re-evaluation of dependent variables, Activity Diary audit, technical troubleshooting, motivational reinforcement, and exercise progression adjustment.
3. Final Intervention Visit (V3 - Week 12): End-of-intervention assessment of dependent variables, final Activity Diary collection, closing adverse event logs, and patient feedback.
4. Post-Intervention Observational Follow-up Visit (V4 - 3 Months Post-Intervention): In-person 35-45 minute evaluation. Signing of the Informed Consent Addendum. Re-assessment of all functional and geriatric variables to measure outcome maintenance. Recording of weekly exercise frequency (days/week), evaluation of regular exercise maintenance, and documentation of post-intervention clinical events (falls, fractures, ER visits, hospital admissions, institutionalization, and mortality).

7. Adherence Monitoring and Safety Management

• Intervention Adherence (12 Weeks): Triangulated through self-reporting (Activity Diary), in-person visit attendance, and biweekly monitoring phone calls (weeks 2, 4, 6, 8, 10, 12). "Adequate intervention adherence" is defined as completing $\ge 80\%$ of planned sessions.

• Post-Intervention Exercise Maintenance: Evaluated at Visit 4 by recording the weekly frequency of structured home exercise. "Maintenance of regular exercise practice" is defined as habitually completing $\ge 3$ of the 5 weekly sessions from the assigned Vivifrail passport.

• Safety Management: Participants receive instructions to contact their GP upon experiencing adverse events (dyspnea, dizziness, severe pain, or falls). Biweekly calls actively screen for incidents. Serious adverse events prompt immediate notification to the Ethics Committee and competent health authorities.

  8. Data Collection, Quality Control, and Custody To ensure quality control and minimize measurement bias, tasks are functionally split: one co-investigator manages initial screening while another conducts in-person evaluations. Data from direct interviews and EMR (Diraya) extraction are pseudonymized using unique alphanumeric codes (e.g., VVM-001) in an Electronic Case Report Form (eCRF).

The master key linking personal identities to codes is stored in an encrypted digital file with restricted access, under the strict custody of the Principal Investigator. Paper CRFs and consents are stored under lock and key. Following Spanish Biomedical Research Law 14/2007 and Data Protection Law 3/2018, all study documentation will be securely retained for a minimum of 5 years (and up to 15 years as outlined in patient information materials) before certified physical and digital destruction.

9. Sample Size Justification Sample size was calculated using G*Power 3.1.9.2 software based on literature reporting 12-week physical exercise impacts on SPPB scores in older adults. Assuming a standardized effect size of 0.33, an alpha error of 0.05, and statistical power of 0.80, a minimum requirement of 60 patients was established. Factoring in an anticipated 30% dropout rate, the final sample size was set at 86 participants.

10. Statistical Analysis Plan Statistical analysis will be performed using SPSS (v25.0) and R Statistical Software (v4.1.2) supported by the Biomedical Research Unit of Hospital Universitario Torrecárdenas.

• Descriptive Analysis: Frequencies/percentages for qualitative variables; means and standard deviations (or median and interquartile ranges) for quantitative variables.

• Normality Testing: Shapiro-Wilk or Kolmogorov-Smirnov tests ($p > 0.05$) based on subgroup sample size.

• Longitudinal Hypothesis Testing: Evolution across the 4 evaluation time points (baseline, week 6, week 12, and 3-month post-intervention follow-up) will be analyzed using repeated-measures ANOVA for normally distributed variables or the Friedman test for non-parametric data, applying Bonferroni corrections for post-hoc pairwise comparisons.

• Stratified Comparisons: Differences across sociodemographic strata (e.g., sex, age groups) will be evaluated using mixed factorial ANOVA or non-parametric equivalents.

• Exploratory Subgroup Analysis: Functional improvement retention will be compared between participants maintaining regular exercise ($\ge 3/5$ sessions/week) versus non-maintainers during the post-intervention phase.

• Post-intervention clinical event frequencies (falls, fractures, ER visits, hospitalizations, institutionalization) will be descriptively reported.

• Predictive Modeling: A multiple linear regression model will be executed to identify baseline clinical and sociodemographic variables associated with greater functional improvement and superior benefit maintenance.

  11. Methodological Limitations The pragmatic Primary Care setting introduces limitations: the single-group pre-post design without a control group prevents isolating efficacy from external confounders (medication changes, social support) or the Hawthorne effect. Single-center execution and voluntary participation may induce selection bias toward self-care-motivated individuals. The home-based intervention limits direct biomechanical exercise supervision, which is mitigated via biweekly calls and diary reviews. Finally, while adding a 3-month post-intervention follow-up allows evaluating medium-term benefit sustainability, the follow-up period remains limited, precluding long-term retention conclusions.

  12. Practical Applicability, Dissemination, and Ethics The study yields a three-tiered impact: enhancing functional autonomy and reducing fall-related fear for patients/caregivers; providing Primary Care staff with an evidence-based exercise prescription tool; and optimizing health system costs by preventing hip fractures and hospitalizations.

• Dissemination: Scientific publications in Geriatrics/Primary Care journals (with sex-disaggregated analyses), presentations at national/international conferences (SEGG, semFYC, EUGMS), executive reports for Andalusian Health Service (SAS) management, local Primary Care clinical sessions/workshops, and community informational talks.

• Ethics: Conducted in strict compliance with the Declaration of Helsinki, Good Clinical Practice, Spanish Biomedical Research Law 14/2007, and Organic Law 3/2018 on Personal Data Protection. The protocol expansion and Visit 4 follow-up phase were formally reviewed and approved by the Ethics Committee (CEI Almería, Protocol V. 2.1, July 3, 2026), incorporating dedicated Patient Information and Informed Consent Addenda.