The Importance of Additional Protein to Benefit More From Training During and After Hospitalization

Study Overview
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Brief Summary
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The purpose of the study is to investigate if an increased protein intake, in the form of a protein-enriched, milk-based supplement, can enhance the beneficial effect of resistance training, offered during hospitalization and 12 weeks post discharge, in older patients. This will in part be evaluated from measures of muscle strength, muscle mass and physical functioning. Also, the study population's acceptance of the intervention product will be assessed along with measures related to 'cost-effectiveness'. A sub-study will be performed in a sub-group (n=30) to investigate if bio-impedance analysis (BIA) correlates with Dual-Energy X-ray absorptiometry (DXA) at single time points, and to see if it is possible to track changes in lean body mass. In addition, the reliability of the bio-impedance analyzer will be evaluated. Also, the prevalence and classification of sarcopenia will be assessed at baseline, and correlations to nutritional status will be investigated (n=120).

Detailed Description
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Main study: The study design is a block randomised, double-blind, placebo-controlled, multicentre intervention study. A total of 120 hospitalized older adults, above 70 years, will be recruited consecutively from the medical departments of three Hospitals in the Capital Region of Denmark (n=40 each place). Participants will be randomized into two groups - one group receives protein-enriched, milk-based supplements and the other group receives iso-energetic placebo products. Both groups participate in the same standardized resistance training program, and will be blinded to the supplement content. One training session consists of three exercises of the lower extremities (3 sets of 10 repetitions, pursuing an intensity of 8-12 repetition maximum (RM)). While admitted, supervised resistance training is offered daily. After discharge, the participants are encouraged to perform the same program as self-training four times per week.To ensure progression (or regression if necessary) the participants receive follow-up home visits by a physiotherapist, and thus after discharge the participants are closely monitored. All participants, irrespective of allocation, will get a daily vitamin D supplement. The study duration for each participant starts while admitted to hospital and lasts until 12 weeks after discharge. Endpoint assessments will be performed at baseline (> 72-h after admission to hospital), after discharge (> 72-h) and 12 weeks (± 2 days) after discharge. A few endpoints will be collected during follow-up (6 months post intervention). Data will be collected by study investigators blinded to the allocation of the participants. Sub-study: 'Validation of a portable bio-impedance analyzer in a population of older adults ≥ 70 years for the assessment of muscle mass and changes in muscle mass over time' A sub-study will be performed to investigate if the portable InBody-230 BIA correlate with DXA at single time points in 30 hospitalized older people ≥ 70 years, and to see if it is possible to track changes in LBM during the 12-week intervention. Total LBM, total fat mass, and percent LBM will be measured and compared as well as appendicular and trunk LBM. In addition, the reliability of the portable bio-impedance analyzer will be evaluated by assessing the degree of agreement between two subsequent measurements. In continuation of recruitment to the primary study, a subset of participants (n=30) will be asked if they want to participate in this sub-study, irrespective of their allocation in the main study. The measurements are going to be performed twice, while hospitalized and 12 weeks after discharge (± 5 days). Sub-study: 'Prevalence of sarcopenia and investigation of the relationship between nutritional status and the EWGSOP conceptual stages for sarcopenia in hospitalized older patients > 70 years'. The prevalence and classification of sarcopenia among Danish hospitalized older patients ≥ 70 years old (n=120) will be evaluated, according to the EWGSOP definition (Hand-grip-strength, 4-m gait speed, Bio-Impedance analysis). Also, examination of the relationship between measurements of nutritional status and the EWGSOP stages for sarcopenia (i.e. no sarcopenia, pre-sarcopenia, sarcopenia and severe sarcopenia) will be assessed at baseline. Nutritional status will be assessed according to BMI (< 18.5, 18.5-20.5, 20.5-25, > 25), Mini Nutritional Assessment (MNA) (no MN, risk of MN, MN), Malnutrition Universal Screening Tool (MUST) (low risk of MN, medium risk of MN, high risk of MN), and NRS-2002 (no MN, mild MN, moderate MN, severe MN) Results will be communicated to the general population and published in peer-reviewed journals.

Official Title
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A Protein-enriched, Milk-based Supplement to Counteract Sarcopenia in Acutely Ill Geriatric Patients Offered Resistance Exercise Training During and After Hospitalisation - a Double-blinded, Randomized Controlled Trial

Conditions
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Sarcopenia

Intervention / Treatment
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* Dietary Supplement: Protein
* Dietary Supplement: Placebo
* Other: Resistance training
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥ 70 years old Able to speak and understand Danish Expected length of stay > 3 days (evaluated by medical staff at department) Ability to stand independently without walking aids Admitted to the medical departments of Gentofte or Herlev Hospital or Rigshospitalet-Glostrup Exclusion Criteria: Active cancer Renal insufficiency (eGFR < 30 mL/min/1.73m2) Cognitive impairment (not able to comprehend the purpose of the study/give informed consent) Terminal disease Exclusively receiving enteral or parenteral nutrition Milk/lactose allergy or intolerance Planning to lose weight/go on a special diet Planned transfer to other hospitals/departments Pacemaker/other implanted electrical stimulants (due to Bio-Impedance Analysis (BIA) measurements) Not being able to lie still in seven minutes (only an exclusion criteria in the sub-study) Withdrawal criteria: Death during admission (does not apply to subsequent admissions) Withdrawal criteria: Discharge/transfer from the medical department before the intervention has started

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resistance training and protein<br>Daily supervised resistance training offered while hospitalized, and encouragement of self-training 4 times per week for duration of 12 weeks after discharge (standardized training program, which will be monitered). Daily intake of 2 x 125 ml protein-enriched, milk-based supplements (whey protein), in the same period (additional  25 g protein and 1953 kJ per day). Daily vitamin D supplements. | Dietary Supplement: Protein<br>* Daily intake of supplement<br>* Other names: Protein-enriched, milk-based supplement (whey protein);Other: Resistance training<br>* Resistance training (offered daily while hospitalized, and encouragement of 4 x/week as self-training after discharge)<br>Dietary Supplement: Vitamin D<br>* Aiming at a dose of 20 ug/day. 20 ug/day will be handed out to study participants who do not get vitamin D supplements from the hospital while admitted and to those who are not already taking vitamin D supplements themselfes e.g. as part of a combination tablet.<br>|
| Placebo Comparator: Resistance training and placebo<br>Daily supervised resistance training offered while hospitalized, and encouragement of self-training 4 times per week for duration of 12 weeks after discharge (standardized training program, which will be monitered). Daily intake of 2 x125 ml iso-energetic placebo-supplements, in the same period. Daily vitamin D supplements. | Dietary Supplement: Placebo<br>* Daily intake of supplement<br>* Other names: Iso-energetic placebo-supplement (no protein);Other: Resistance training<br>* Resistance training (offered daily while hospitalized, and encouragement of 4 x/week as self-training after discharge)<br>Dietary Supplement: Vitamin D<br>* Aiming at a dose of 20 ug/day. 20 ug/day will be handed out to study participants who do not get vitamin D supplements from the hospital while admitted and to those who are not already taking vitamin D supplements themselfes e.g. as part of a combination tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 30-s chair stand performance | Number of stand-ups from a chair in 30 seconds (modified version, help from armrests are allowed). | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total lean body mass | Lean body mass (kg and percent) evaluated by bio-impedance analysis (portable, dual-frequency, 8-Point Tactile Electrode System). | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Appendicular lean body mass | Appendicular lean body mass (kg and percent) evaluated by bio-impedance analysis (portable, dual-frequency, 8-Point Tactile Electrode System). | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Trunk lean body mass | Trunk lean body mass (kg and percent) evaluated by bio-impedance analysis (portable, dual-frequency, 8-Point Tactile Electrode System). | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in hand grip strength | Isometric hand grip strength (kg) (Saehan Medical digital dynamometer, 2012). | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in 4 m gait speed | The time used for walking 4 m (m/s and s ) | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in Activities of daily living (ADL) | Use of Barthel-100 | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in mobility | Use of De Morton Mobility Index (DEMMI) | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in cognitive functioning | Use of Mini Mental State Examination (MMSE) | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Use of home care | Interview: (yes/no) | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Residence | Interview: (own home, nursing home/assisted living facility, 24-hour rehabilitation facility) | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Use of gait aid | Interview: yes/no/cannot walk and registration of specific gait help | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Length of hospital stay (LOS) | The in-hospital intervention period (date of recruitment until date of discharge) (days) | Day of discharge (from hospital) | 
| Readmission to hospital | Frequency (number) | From discharge until 12 weeks post discharge, and 6 months post discharge | 
| Length of total hospital stay for readmissions | Total length (days). | From discharge until 12 weeks post discharge, and 6 months post discharge | 
| Mortality | Mortality (yes/no) | From discharge until 12 weeks post discharge, and 6 months post discharge | 
| Change in health related Quality of life | Questionnaire: Euroqol EQ-5D-3L | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Change in Body weight | Measured to the nearest 0.1 kg using a calibrated scale | Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge | 
| Study population acceptance of product | Self-administered evaluation-questionnaire | 12 weeks post discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, Muscular atrophy, Frailty, Acute illness, Ageing, Protein supplementation, Whey protein, Resistance training, Strength training