The VOILA Intervention Study (VOILA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Combination product: VOILA

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: P. Eline Slagboom, PhD; Phone Number: 31 0653879941; Email: P.Slagboom@lumc.nl
• Study Contact Backup: Name: Jordi Morwani Mangnani, MSc; Email: j.morwani_mangnani@lumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6708 WE
      • Recruiting
      • Wageningen University & Research
      • Contact: Lisette de Groot, PhD; Email: lisette.degroot@wur.nl
      • Contact: Charlotte Kramer, MSc; Email: charlotte.kramer@wur.nl
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Recruiting
      • Maastricht University Medical Center
      • Contact: Lex Verdijk, PhD; Email: lex.verdijk@maastrichtuniversity.nl
      • Contact: Alejandra Monsegue, MSc; Email: a.monsegue@maastrichtuniversity.nl
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZC
      • Recruiting
      • Leiden University Medical Center
      • Contact: Jordi Morwani Mangnani, MSc; Email: j.morwani_mangnani@lumc.nl
      • Contact: P. Eline Slagboom, PhD; Email: j.morwani_mangnani@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Active reference group; Only baseline measurements will be done.
Experimental: Metabolically compromised group; Group with metabolomic mortality scores above threshold will undergo intervention. Baseline and endline measurements.	Combination product: VOILA; 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.
Experimental: Mobility compromised; Group with walking aids will undergo intervention. Baseline and endline measurements.	Combination product: VOILA; 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.
Experimental: Knee replacement INT; Group with recent knee replacement surgery will undergo intervention. Baseline and endline measurements.	Combination product: VOILA; 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.
No Intervention: Knee replacement Control; Group with recent knee replacement surgery will undergo standard care. Baseline and endline measurements.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Maastricht University Medical Center; FrieslandCampina; ZonMw: The Netherlands Organisation for Health Research and Development; Wageningen University and Research
• Investigators: Principal Investigator: P. Eline Slagboom, PhD, Leiden University Medical Center; Principal Investigator: Lex Verdijk, PhD, Maastricht University Medical Center; Principal Investigator: Lisette de Groot, PhD, Wageningen University & Research

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: April 15, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 26, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Nutrition; Mobility; Resistance Training; Gut microbiome; Protein supplement; Immunometabolsim
• Other Study ID Numbers: NL76879.058.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Clinical data in this project will only be shared within the constraints of the informed consent. Furthermore for all permitted sharing, a data access committee (DAC) has been established in which the responsible PI of each center is present, a secretary and data manager. The data will primarily be analysed by the centers generating the data and associated partners in the VOILA project. In a later stage data access can be requested at the central contact person P.E. Slagboom (p.slagboom@lumc.nl ) and permitted by the DAC and analysed locally provided a data access agreement is signed.
• IPD Sharing Time Frame: Length is not determined.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

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