The VOILA Intervention Study

Study Overview
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Brief Summary
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The multi-disciplinary and translational VOILA project presents a unique intersection between gut, immuno-metabolic, and musculoskeletal health. The main goals of the project are to develop biomarkers for healthy aging and prevent disease by maintaining quality of life in older adults. Within this umbrella project, the multimodal VOILA lifestyle intervention study will assess the impact of a twelve-week strength training and nutritional intervention in older adults with different degrees of mobility. The study will improve the current understanding of the complex relationship between gut and muscle health in different segments of mobility and obtain an insight into the heterogeneity of responsiveness between individuals.

Official Title
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Vitality Oriented Innovation for the Lifecourse of the Ageing Society Intervention Study

Conditions
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Aging

Intervention / Treatment
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* Combination Product: VOILA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥70 years A body mass index of 18.5-35.0 kg/m2 Able to give written informed consent Community-dwelling Mentally competent with a Mini-Mental State Examination (MMSE) score of ≥24 points Able to follow the study protocol Additional group-specific criteria: Metabolically compromised group - Framingham Risk Score ≥14 and Metabolomic Mortality Score of ≥0.173 Reduced mobility group - People able to walk but needing walking aids to walk anywhere outside their house Total knee replacement intervention and control group - Discharged from MUMC+ after undergoing elective knee replacement surgery (intervention starts  4 weeks after surgery) Active reference group People who meet the Nederlandse Norm Gezond Bewegen. This means they partake in at least moderate exercise for at least 30 minutes on 5 days of the week, as determined by the SQUASH questionnaire (40). Framingham Risk Score of <14 and Metabolic Mortality Score of <0.173 Exclusion Criteria: Already using prebiotic fibres* Use of laxatives* Not willing to stop using dietary supplements in high doses (high doses: 0.10*Upper Level or more)* Following a structured, intense exercise programme (currently or in the last year)* Allergic, intolerant or hypersensitive to milk/lactose (self-reported)* Dietary restrictions on milk/lactose/prebiotics/vitamin D/calcium consumption* Abnormal hepatic or renal laboratory parameters (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (screening) or contra-indication by treating medical practitioner (data from hospital) Diagnosis of disorders/diseases in which a high protein intake can be harmful, such as renal impairment or failure, liver disease, or diabetes associated with nephropathy (treating medical practitioner has the decisive voice). Diseases, conditions or disorders which may affect the ability to follow the study protocol and which cannot be overcome with help of a caregiver Any other medical condition that may interfere with the safety of the participants during training or assessment of the outcome parameters, in the investigators' judgement Current participation in other scientific research that conflicts with this study (e.g. intervention studies or weight management studies) Not signed up to a general practitioner No permission to request information from the general practitioner/ treating specialist(s) about medical history, medication use. Specific for TKR group: Referral to rehabilitation facility after hospital discharge Osteoarthritis of the knee secondary to septic arthritis, osteonecrosis, fracture, osteochondritis dissecans, or malignant processes Collagen disorders, e.g. Marfan and Ehler-Danlos Total hip prosthesis or TKR in both legs

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Active reference group<br>Only baseline measurements will be done. | |
| Experimental: Metabolically compromised group<br>Group with metabolomic mortality scores above threshold will undergo intervention. Baseline and endline measurements. | Combination Product: VOILA<br>* Participants will be given dietary supplement powder containing protein, galactooligosaccharide (GOS), vitamin D, and calcium throughout the twelve weeks of intervention. This will be accompanied with a resistance training regime whereby participants will train three times a week for the three months. A variety of measurements will be carried out at baseline and at endline.<br>|
| Experimental: Mobility compromised<br>Group with walking aids will undergo intervention. Baseline and endline measurements. | Combination Product: VOILA<br>* Participants will be given dietary supplement powder containing protein, galactooligosaccharide (GOS), vitamin D, and calcium throughout the twelve weeks of intervention. This will be accompanied with a resistance training regime whereby participants will train three times a week for the three months. A variety of measurements will be carried out at baseline and at endline.<br>|
| Experimental: Knee replacement INT<br>Group with recent knee replacement surgery will undergo intervention. Baseline and endline measurements. | Combination Product: VOILA<br>* Participants will be given dietary supplement powder containing protein, galactooligosaccharide (GOS), vitamin D, and calcium throughout the twelve weeks of intervention. This will be accompanied with a resistance training regime whereby participants will train three times a week for the three months. A variety of measurements will be carried out at baseline and at endline.<br>|
| No Intervention: Knee replacement Control<br>Group with recent knee replacement surgery will undergo standard care. Baseline and endline measurements. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle mass | appendicular lean mass in kg (DEXA) | 10 weeks | 
| Muscle function | 5-times repeated chair rise test in seconds | 10 weeks | 
| Gut health | bifidobacteria (from stool sample) in log10 cells per gram dried faeces | 10 weeks | 
| Immuno-metabolic health - GLC | fasting blood glucose (GLC) in mmol/L | 10 weeks | 
| Immuno-metabolic health - GlycA | glycoprotein acetyls (GlycA) in mmol/L | 10 weeks | 
| Immuno-metabolic health - VLDL | very low-density lipoprotein (VLDL)-diameter in nm (from Nightingale 1H NMR platform) | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle function - SPPB | Short Physical Performance Battery (SPPB) | 10 weeks | 
| Muscle function - TUG | Timed Up and Go test (TUG) | 10 weeks | 
| Muscle function - 6MWT | 6-minute walking test (6MWT) | 10 weeks | 
| Muscle function - 1RM | 1 repetition maximum test (1RM) as measured on exercise machines | 10 weeks | 
| Body composition - Whole body regional lean mass | DEXA whole body lean mass in kg | 10 weeks | 
| Body composition - Whole body regional fat mass | DEXA whole body fat mass in kg | 10 weeks | 
| Body composition - Regional lean mass | DEXA regional lean mass in kg | 10 weeks | 
| Body composition - Regional fat mass | DEXA regional fat mass in kg | 10 weeks | 
| Immuno-metabolic health - Hba1c | haemoglobin A1c (Hba1c) | 10 weeks | 
| Immuno-metabolic health - Insulin | Insulin in mol/L | 10 weeks | 
| Immuno-metabolic health - Blood pressure | Blood pressure in mmHg | 10 weeks | 
| Knee replacement group additional outcomes - CT | Single-slice CT-scans midway the upper legs | 10 weeks | 
| Knee replacement group additional outcomes - WOMAC | Western Ontario and McMaster Universities Arthritis Index (WOMAC). | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistance Training, Nutrition, Protein supplement, Gut microbiome, Immunometabolsim, Mobility