Effectiveness of Combined Therapeutic Exercise and Anti-Inflammatory Nutritional Supplementation in Frail, Malnourished Older Adults
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 158
- 主要终点
- Short Physical Performance Battery (SPPB)
研究概览
简要总结
The goal of this clinical trial is to evaluate whether a combined intervention of therapeutic exercise and anti-inflammatory nutritional supplementation improves physical performance and reduces systemic inflammation in frail, malnourished older adults. The main questions it aims to answer are:
Does the addition of an anti-inflammatory nutritional supplement (Alisenoc™) to a multicomponent exercise program (Vivifrail) lead to greater improvements in physical performance compared to standard exercise and conventional nutritional support?
Does the combined intervention reduce levels of inflammatory biomarkers (e.g., IL-6, TNF-α, IL-8, GDF-15) in this population?
Are there measurable changes in body composition (e.g., muscle mass, fat mass, bone health) following the intervention?
Does the intervention impact clinical outcomes such as hospital readmissions, functional independence, or mortality over the following 12 months?
Researchers will compare two groups:
One group receiving the Vivifrail exercise program plus a daily dose of the anti-inflammatory nutritional supplement Alisenoc™.
Another group receiving the same Vivifrail program plus an isocaloric, protein-equivalent conventional supplement.
Participants will:
Be aged 75 years or older and identified as frail and malnourished according to Fried and GLIM criteria.
Undergo baseline evaluation including functional performance (SPPB), body composition via bioimpedance analysis, and blood sample collection for inflammatory biomarkers.
Be randomly assigned to one of the two intervention groups.
Follow a 12-week home-based multicomponent exercise program guided by educational materials and supervised remotely.
Consume the assigned oral nutritional supplement daily for the same 12-week period.
Return for outcome assessments at 12 weeks, and again at 6 and 12 months for long-term follow-up.
All study procedures will take place at the Hospital Universitario de Navarra (HUN), Spain. Participants will be recruited from outpatient geriatrics and nutrition clinics and assessed at a dedicated research unit with nursing support. The intervention is designed to be feasible, scalable, and representative of real-world multidisciplinary care in older populations with high vulnerability.
The study aims to provide evidence for an integrative, personalized approach to reversing frailty through combined physical and nutritional strategies targeting the biological basis of inflammaging.
详细描述
Frailty and malnutrition are prevalent, closely interconnected syndromes in older adults, associated with adverse outcomes such as functional decline, falls, institutionalization, prolonged hospitalization, and increased mortality. These conditions reinforce each other in a bidirectional cycle: malnutrition contributes to muscle loss and diminished physical function, while frailty can lead to decreased appetite and nutrient intake. Both are increasingly linked to chronic, low-grade systemic inflammation, known as "inflammaging."
Inflammaging is characterized by persistently elevated levels of circulating pro-inflammatory cytokines, such as IL-6, TNF-α, IL-8, and CRP. This inflammatory environment contributes to sarcopenia, bone demineralization, insulin resistance, and immune system decline, all of which further drive the progression of frailty. Therefore, interventions that reduce inflammaging may offer a novel therapeutic pathway to mitigate frailty and its consequences.
Multicomponent physical exercise programs-especially those incorporating strength, balance, and endurance training-have demonstrated efficacy in improving mobility and reducing inflammation in older adults. The Vivifrail© program, developed and validated for frail and pre-frail populations, offers a structured, scalable home-based exercise model. At the same time, nutritional interventions enriched with anti-inflammatory ingredients-such as extra virgin olive oil polyphenols, omega-3 fatty acids (EPA/DHA), and leucine-may support muscle anabolism and reduce systemic inflammation. Yet, despite promising evidence from each modality alone, their combined impact in frail, malnourished populations remains understudied.
The AliFrail trial addresses this gap through a randomized, controlled, open-label, two-arm clinical study conducted at the Hospital Universitario de Navarra (HUN) in Pamplona, Spain. A total of 158 community-dwelling adults aged ≥75 years with frailty and malnutrition will be randomized to receive either:
- the Vivifrail© exercise program plus a daily anti-inflammatory oral nutritional supplement (Alisenoc™), or
- the same exercise program with an isocaloric, protein-equivalent standard nutritional supplement without anti-inflammatory components.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged ≥ 75 years.
- •Diagnosis of frailty according to Linda Fried's criteria.
- •Diagnosis of malnutrition according to GLIM (Global Leadership Initiative on Malnutrition) criteria.
- •Barthel Index score ≥ 60 points.
- •Absence of advanced chronic kidney disease (defined as glomerular filtration rate < 25 mL/min/1.73m²).
- •Absence of terminal illness as defined by SECPAL (Spanish Society for Palliative Care) criteria.
排除标准
- •Presence of type 1 or type 2 diabetes mellitus with poor metabolic control (HbA1c > 8% or insulin-dependent).
- •Oropharyngeal dysphagia to liquids that prevents safe intake of oral supplementation.
- •Moderate-to-severe cognitive impairment, defined as a score ≥ 5 on the Global Deterioration Scale (GDS) of Reisberg.
- •Refusal to sign the informed consent by the patient, primary caregiver, or legal representative, or inability to obtain it.
- •Known allergy or intolerance to any component of the study supplements.
- •Institutionalized in a long-term care or residential facility.
结局指标
主要结局
Short Physical Performance Battery (SPPB)
时间窗: From baseline to 12 weeks after intervention start
Change in physical performance assessed by the Short Physical Performance Battery (SPPB), a validated composite measure of lower extremity function. The SPPB includes three components: balance tests, gait speed, and repeated chair stands. Scores range from 0 to 12, with higher scores indicating better physical function and mobility.
次要结局
- Phase Angle (PhA)(Baseline, 12 weeks)
- Skeletal Muscle Mass Index (SMMI)(Baseline, 12 weeks)
- Inflammatory Biomarkers(Baseline and 12 weeks post-intervention)
- Handgrip Strength (Jamar® Dynamometer)(Baseline, 12 weeks, post-intervention)
- Barthel Index Score(Baseline, 12 weeks, and 12 months post-intervention)
- Lawton & Brody Instrumental Activities of Daily Living (IADL) Scale Score(Baseline, 12 weeks, and 12 months post-intervention)
- Fried's Frailty Phenotype Score(Baseline and 12 weeks post-intervention)
- EuroQol 5-Dimension 3-Level Questionnaire (EQ-5D-3L) Score(Baseline, 12 weeks post-intervention)
- Adherence, Safety, and Tolerability of the Intervention(Baseline, 12 weeks post-intervention)
- Clinical Adverse Events: Readmissions, Falls, and Mortality(12 weeks, and 12 months post-intervention)