Clinical trial NCT03842579: Protein and Exercise to Counteract Frailty in Older Adults
Official title: Effects of High-protein Diet Combined With Exercise to Counteract Frailty in Pre-frail and Frail Community-dwelling Older Adults: a Three-arm Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Physical Frailty
Keywords: Frailty
Ageing
High-Protein diet
Protein Supplementation
Resistance Training
Strength Training
Muscle Power
Muscle Strength
Muscle Mass
Functional Performance
Nutritional Status
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Metropolitan University College
name: Municipality of Odense, Denmark
name: Arla Foods
First posted: 2019-02-15
Enrollment: 150
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of interventions with high-protein diet alone or in combination with resistance training on muscle mechanical function (muscle power and strength), frailty status, functional performance, muscle mass and quality of life.

Detailed description: Study design: two-phase randomized controlled trial with three arms.

Phase 1 stabilization phase lasting one month. Participants with low protein intake (\<1.0 g/kg/day) are provided with national guidelines for daily protein intake and publicly available information material and recommended to increase their protein intake to meet the guidelines. Compliance to the recommendation/ guidelines (eating \>1.0 g/kg/day) will be evaluated by 4-day food records at the end of the stabilization phase. Only compliant participants are eligible for phase 2. Participants that are not compliant will be followed as "natural observational group" but will not be considered for the primary statistical analysis. Data collection in these participants will only include assessment of selected demographic, functional and nutritional parameters and semi-structured interviews to identify potential barriers for not improving protein intake. Semi-descriptive data will be presented if possible.

Phase 2: Three-arm randomized controlled trial lasting four months:

i) Protein-only (PROT): participants will receive milk-based protein-rich products with the aim of targeting a daily protein intake of 1.5 g/kg; ii) Exercise and Protein (EXEPROT): participants will receive the protein intervention as in the PROT-group combined with progressive explosive type heavy-resistance strength training two times per week iii) Recommendations (REC) participants receive the national nutritional recommendations for older adults and are recommended to follow these recommendations over the course of the study.

Nutritional data will be collected pre and post the stabilization phase. Collection of the primary and secondary outcomes will occur at baseline (pre phase 2) and at the 4-month follow-up (post phase 2). Nutritional assessment will also be evaluated halfway, at the 2-month follow-up.

Compliance Adherence to the exercise protocol and protein supplementation is recorded during the study. For the exercise protocol adherence will be considered as achieving minimum to 75% of valid training sessions, considered as minimum 70% of the exercises planned for each session. For the protein supplementation, adherence will be evaluated as daily protein intake of ≥ 1.35 g/kg (estimated from 24 hours recall and four-day food records) at the 2-month follow-up and at the 4-months follow-up. Compliance will also be estimated from during each delivery of products with a set of questions (e.g. how much of the supplement is consumed? Any changes to the habitual food intake?) and regular phone follow-ups. If participants are unable to reach the protein target additional face to face or phone interview will be planned to support adherence. For the REC-group adherence is defined as following the recommended intake of protein (1.0-1.3 g/kg/day).

Sample size and statistics Lower leg muscle power is the primary outcome of this study. Due to lack of studies similar to this study design (e.g. age and frailty status of the participants, type of exercise and level of protein supplementation) the investigators have calculated sample size using a combination of studies and methods. Based on findings from a 2017 study the effect of 12-weeks of protein supplementation (two daily supplements of 20 g milk protein) in combination with resistance training in +80-year-old healthy adults increased muscle power by 15% (SEM ± 5%) in comparison with -7% (SEM ± 6%) in the control group (receiving protein supplementation only). A result from a 2018 study indicate that 12 weeks of nutritional supplementation (0.8 g/kg/day, 1.2 g/kg/day or 1.5 g/kg/day) to pre-frail or frail older adults \>70 years resulted in an increase in muscle mass (estimated by Dual energy X-ray Absorptiometry, DXA) of approximately 4% in the group receiving 1.5 g/kg/day. Unpublished data from the investigators research group show that change in muscle mass (estimated by DXA) accounted for 1,95% of the change in muscle power in older adults following 12 weeks of resistance training. Hence, the estimated effect of an increase in muscle mass of 4% on muscle power is 7,8%. Adding this to the results from the 2017 study gives an estimated change on 0,8% in the PROT-group. Assuming, that the change in muscle mass are comparable in the three groups the investigator therefore expect a change in muscle power of 15%, 0,8% and -7% with a standard deviation (SD) of 30 in the EXEPROT-, PROT- and REC-group, respectively.

Setting a power of 0.8 sample size with 37 participants in each arm should be enough to detect a significant difference in muscle power (significance level at 0.05). Adding 25% to account for dropouts a total of 150 participants is needed.

Intention-to-treat analysis will be performed. In addition, per-protocol analysis of participants that are compliant to the protocol will be performed.

Eligibility criteria: Inclusion Criteria:

* Community-dwelling adults ≥ 80 years
* Pre-frail or frail (evaluated by the physical frailty questionnaire, SHARE-FI75+)
* Intact cognitive function (Mini Mental State Evaluation ≥4)
* Medically stable evaluated by medical screening including blood sample
* Able to participate in group-based exercise without personal assistance
* Able to understand, read and write Danish

Exclusion Criteria:

* Allergic/ intolerant to the interventions (kidney diseases, lactose intolerance etc.)
* On a weight losing diet

Primary outcomes:
measure: Changes from baseline lower leg muscle power at 4 months
timeFrame: Baseline and 4-month follow-up
Secondary outcomes:
measure: Changes from baseline physical frailty status at 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline countermovement jump muscle power at 4 months
timeFrame: Baseline and 4-month follow-up
measure: Changes from baseline leg press and handgrip muscle strength at 4 months
timeFrame: Baseline and 4-month follow-up
measure: Changes from baseline Short Physical Performance Battery test at 4 months
timeFrame: Baseline and 4-month follow-up
measure: Eating Symptom Questionnaire
timeFrame: Baseline
measure: Risk of Dysphagia
timeFrame: Baseline
measure: Appetite
timeFrame: Baseline
measure: Changes from baseline anthropometry waist and hip circumference at 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline body weight at 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline lean and fat mass at 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline lean and fat mass and bone mineral density) to 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline Health-related quality of life to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline pain to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline fatigue and fatigability to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline activities of daily living to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline fear of falling to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline Blood markers to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Chenages from baseline Objective measures of Physical activity, sedentary behaviour, nap and sleep to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline Self-reported Physical activity & sedentary behaviour to 4 months
timeFrame: Baseline and 4-months follow-up
measure: Changes from baseline Dietary intake to 4 month
timeFrame: Baseline and 4-months follow-up
measure: 24 hours recall
timeFrame: pre phase 1
measure: Changes from baseline Walking speed to 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline Stand and reach to 4 months
timeFrame: Baseline to 4 months follow-up
measure: Changes from baseline Walking distance to 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes from baseline Upper body ball throwing to 4 months
timeFrame: Baseline to 4 months follow-up
measure: Changes from baseline Rising from laying position to 4 months
timeFrame: Baseline to 4 months follow-up
measure: Changes from baseline Nutritional status to 4 months
timeFrame: Baseline and 4 months follow-up
measure: Changes in Risk of poor protein intake to 4 months
timeFrame: Baseline and 4 months
Other outcomes:
measure: Cognitive function
timeFrame: Baseline and 4-months follow-up
measure: Gender
timeFrame: Baseline
measure: Age
timeFrame: Baseline
measure: Education
timeFrame: Baseline
measure: Marital status
timeFrame: Baseline
measure: Depression
timeFrame: Baseline
measure: Incontinence
timeFrame: Baseline
measure: Chronic conditions
timeFrame: Baseline
measure: Use of medicine
timeFrame: Baseline
Locations:
city: Odense
country: Denmark
facility: University of Southern Denmark
Study officials:
affiliation: University of Southern Denmark
name: Paolo Caserotti, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bechshoft RL, Malmgaard-Clausen NM, Gliese B, Beyer N, Mackey AL, Andersen JL, Kjaer M, Holm L. Improved skeletal muscle mass and strength after heavy strength training in very old individuals. Exp Gerontol. 2017 Jun;92:96-105. doi: 10.1016/j.exger.2017.03.014. Epub 2017 Mar 28.
citation: Park Y, Choi JE, Hwang HS. Protein supplementation improves muscle mass and physical performance in undernourished prefrail and frail elderly subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2018 Nov 1;108(5):1026-1033. doi: 10.1093/ajcn/nqy214.
citation: Buhl SF, Beck AM, Christensen B, Caserotti P. Effects of high-protein diet combined with exercise to counteract frailty in pre-frail and frail community-dwelling older adults: study protocol for a three-arm randomized controlled trial. Trials. 2020 Jul 11;21(1):637. doi: 10.1186/s13063-020-04572-z.