Clinical trial NCT02717819: The Importance of Additional Protein to Benefit More From Training During and After Hospitalization
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sarcopenia
Keywords: Sarcopenia
Muscular atrophy
Frailty
Acute illness
Ageing
Protein supplementation
Whey protein
Resistance training
Strength training
Lead sponsor: Copenhagen University Hospital at Herlev
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: The Danish Dairy Research Foundation, Denmark
name: Arla Foods
name: Glostrup University Hospital, Copenhagen
name: University Hospital, Gentofte, Copenhagen
First posted: 2016-03-24
Enrollment: 165
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in 30-s chair stand performance
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
Secondary outcomes:
measure: Total lean body mass
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Appendicular lean body mass
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Trunk lean body mass
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in hand grip strength
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in 4 m gait speed
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in Activities of daily living (ADL)
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in mobility
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in cognitive functioning
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Use of home care
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Residence
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Use of gait aid
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Length of hospital stay (LOS)
timeFrame: Day of discharge (from hospital)
measure: Readmission to hospital
timeFrame: From discharge until 12 weeks post discharge, and 6 months post discharge
measure: Length of total hospital stay for readmissions
timeFrame: From discharge until 12 weeks post discharge, and 6 months post discharge
measure: Mortality
timeFrame: From discharge until 12 weeks post discharge, and 6 months post discharge
measure: Change in health related Quality of life
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Change in Body weight
timeFrame: Baseline (admission to hospital), within 3 days of discharge, and 12 weeks after discharge
measure: Study population acceptance of product
timeFrame: 12 weeks post discharge
Other outcomes:
measure: Lean body mass (sub group n=30)
timeFrame: Baseline (while admitted to hospital) and 12 weeks post discharge
measure: Fat mass (sub group n=30)
timeFrame: Baseline (while admitted to hospital) and 12 weeks post discharge
measure: Reliability of bio-impedance analyzer in sub-group (n=30)
timeFrame: Baseline (while admitted to hospital)
measure: Prevalence of sarcopenia
timeFrame: Baseline (while admitted to hospital)
measure: Classification of sarcopenia
timeFrame: Baseline (while admitted to hospital)
measure: Nutritional status - Body mass index (BMI)
timeFrame: Baseline (while admitted to hospital)
measure: Nutritional status - Mini Nutritional Assessment (MNA)
timeFrame: Baseline (while admitted to hospital)
measure: Nutritional status - Malnutrition Universal Screening Tool (MUST)
timeFrame: Baseline (while admitted to hospital)
measure: Nutritional status - Nutritional Risk Screening 2002 (NRS-2002)
timeFrame: Baseline (while admitted to hospital)
measure: Energy intake
timeFrame: 4 days while admitted to hospital, or shorter if discharged
measure: Protein intake
timeFrame: 4 days while admitted to hospital, or shorter if discharged
measure: Energy intake
timeFrame: From discharge until 12 weeks post discharge
measure: Protein intake
timeFrame: From discharge until 12 weeks post discharge
measure: Level of daily activity
timeFrame: From discharge until 12 weeks post discharge
Locations:
city: Gentofte
country: Denmark
facility: Copenhagen University Hospital Gentofte
city: Glostrup
country: Denmark
facility: Rigshospitalet-Glostrup
city: Herlev
country: Denmark
facility: Copenhagen University Hospital Herlev
Study officials:
affiliation: Copenhagen University Hospital at Herlev
name: Arne Astrup, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gade J, Beck AM, Andersen HE, Christensen B, Ronholt F, Klausen TW, Vinther A, Astrup A. Protein supplementation combined with low-intensity resistance training in geriatric medical patients during and after hospitalisation: a randomised, double-blind, multicentre trial. Br J Nutr. 2019 Nov 14;122(9):1006-1020. doi: 10.1017/S0007114519001831.
citation: Gade J, Beck AM, Bitz C, Christensen B, Klausen TW, Vinther A, Astrup A. Protein-enriched, milk-based supplement to counteract sarcopenia in acutely ill geriatric patients offered resistance exercise training during and after hospitalisation: study protocol for a randomised, double-blind, multicentre trial. BMJ Open. 2018 Feb 1;8(2):e019210. doi: 10.1136/bmjopen-2017-019210.