Protein and Exercise to Counteract Frailty in Older Adults

Physical Frailty Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03842579
• Other study ID #: S-20180048
• Secondary ID: S-20180048
• Status: Recruiting
• Phase: N/A
• Start date: February 13, 2019
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2020
• Source: University of Southern Denmark
• Contact: Sussi F. Buhl, PhD.Stud
• Phone: +45 65 50 89 24
• Email: sbuhl[@]health.sdu.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Frailty
• Physical Frailty

Intervention

Other:
• Resistance training
Supervised progressive explosive type heavy-resistance training two times per week
• High-protein diet
Daily supplementation with milk-based protein-rich products
• Recommendations
Provided with the official national recommendations on nutrition

Locations

Country	Name	City	State
Denmark	University of Southern Denmark	Odense

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern Denmark	Arla Foods, Metropolitan University College, Municipality of Odense, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

Bechshøft RL, Malmgaard-Clausen NM, Gliese B, Beyer N, Mackey AL, Andersen JL, Kjær 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive function	The Digit Symbol Substitution Test	Baseline and 4-months follow-up
Other	Gender	Gender (male female)	Baseline
Other	Age	Age (years)	Baseline
Other	Education	Self-report education will be assessed as number of years spent in school and maximum level of education achieved.	Baseline
Other	Marital status	Marital status will be evaluated as self-report.	Baseline
Other	Depression	depression will be evaluated with validated questionnaire at baseline (Geriatric Depression	Baseline
Other	Incontinence	Incontinence will be evaluated with the International Consultation on Incontinence Questionnaire (ICIQ) questionnaire at baseline (max score 21)	Baseline
Other	Chronic conditions	Number and type of chronic conditions will be assessed as self-report	Baseline
Other	Use of medicine	Direct count of name and dose of medicines performed under medical screening. The participant will be asked to bring the medicines.	Baseline
Primary	Changes from baseline lower leg muscle power at 4 months	Lower leg muscle power will be assessed unilaterally using the Nottingham Leg Rig	Baseline and 4-month follow-up
Secondary	Changes from baseline physical frailty status at 4 months	Changes in frailty status will be evaluated by the physical frailty questionnaire (SHARE-FI75+) and the slightly modified version of the Frailty Phenotype assessment tool developed by Fried.	Baseline and 4 months follow-up
Secondary	Changes from baseline countermovement jump muscle power at 4 months	Weight-bearing multi-joint motor task, countermovement jump, with a linear encoder.	Baseline and 4-month follow-up
Secondary	Changes from baseline leg press and handgrip muscle strength at 4 months	Lower limb muscle strength will be measured during a maximal voluntary isometric leg press test (MVC). Subjects are seated in a custom-built unilateral leg press device (knee and ankle angles of 120 and 90, respectively) while pushing against a fixed instrumented force plate as hard and fast as possible with the dominant leg against. Muscle strength, contractile Rate of Force Development (RFD) and impulse will be determined in the trial with the highest resultant peak force.; Handgrip: Maximal isometric handgrip strength will be assessed unilaterally using a handheld dynamometer	Baseline and 4-month follow-up
Secondary	Changes from baseline Short Physical Performance Battery test at 4 months	Physical function will be measured with the Short Physical Performance Battery (SPPB) which consists of three items (balance, 3 or 4 meters walking and repeated chair rise). Score ranges from 0-12 (each item has a score between 0 and 4).	Baseline and 4-month follow-up
Secondary	Eating Symptom Questionnaire	Evaluated by a validated eating ability questionnaire. For each symptom participant range from none to severe.	Baseline
Secondary	Risk of Dysphagia	Evaluated by a validated questionnaire, the EAT-10. Resulting in a score ranging from 0-40	Baseline
Secondary	Appetite	Evaluated by a validated questionnaire the Simplified Nutritional Appetite Questionnaire. Score range from 4-20.	Baseline
Secondary	Changes from baseline anthropometry waist and hip circumference at 4 months	Waist and hip circumference (cm) will be measured using a standard ruler.	Baseline and 4 months follow-up
Secondary	Changes from baseline body weight at 4 months	Body weight will be measured to using a transportable scale. Participants will be measured without shoes and wearing light clothing.	Baseline and 4 months follow-up
Secondary	Changes from baseline lean and fat mass at 4 months	Changes in lean mass and fat mass will be estimated by Bioelectrical Impedance Analysis.	Baseline and 4 months follow-up
Secondary	Changes from baseline lean and fat mass and bone mineral density) to 4 months	Changes in body composition (lean and fat mass and bone mineral density) will be measured by Dual-energy X-ray Absorpmetry.	Baseline and 4 months follow-up
Secondary	Changes from baseline Health-related quality of life to 4 months	Health-related quality of life questionnaires (EQ-5D-3L and SF-12) will be used. Scores range from 11111-33333 and 0-100, respectively.	Baseline and 4-months follow-up
Secondary	Changes from baseline pain to 4 months	Pain will be assessed by validated questionnaires (The brief pain inventory & Back and Neck pain survey questionnaire). Visual analogue scale (score 0-10) is combined with questions about intensity and frequency of pain.	Baseline and 4-months follow-up
Secondary	Changes from baseline fatigue and fatigability to 4 months	Validated questionnaires will be used to assess fatigue and fatigability (Mobility Fatigue, Mob-T, & The Pittsburgh Fatigability Scale). Scores ranging from 0-6 and 0-50, respectively.	Baseline and 4-months follow-up
Secondary	Changes from baseline activities of daily living to 4 months	Activities of daily living will be assessed with self-report questionnaires.	Baseline and 4-months follow-up
Secondary	Changes from baseline fear of falling to 4 months	Validated questionnaire will be used to assess fear of falling (the Falls Efficacy Scale - International). Score range from 16-64.	Baseline and 4-months follow-up
Secondary	Changes from baseline Blood markers to 4 months	Analysis of changes in markers of health and disease will be performed, e.g. Lipid profile, Hormonal profile, protein-markers of inflammation (e.g. High Sensitive C-Reaktivt Protein (HS-CRP), soluble urokinase plasminogen activating receptor (suPAR)), vitamins and minerals.	Baseline and 4-months follow-up
Secondary	Chenages from baseline Objective measures of Physical activity, sedentary behaviour, nap and sleep to 4 months	Accelerometry methodology: level and patterns of physical activity (PA), sedentary behaviour (SB), nap and sleep (NAS) will be assessed with commercially available accelerometers (e.g. Axivity, Actigraph) placed on different anatomic locations (e.g. thigh, hip) for one week.	Baseline and 4-months follow-up
Secondary	Changes from baseline Self-reported Physical activity & sedentary behaviour to 4 months	Self-report questionnaire will be used to assess physical activity and sedentary behaviour (e.g. sedentary behaviour questionnaires).	Baseline and 4-months follow-up
Secondary	Changes from baseline Dietary intake to 4 month	Dietary intake is estimated by Four-day food records and food frequency questionnaires. Protein intake is calculated as average g/day and g/kg/day.	Baseline and 4-months follow-up
Secondary	24 hours recall	Dietary intake is estimated from 24 hours recall. Protein intake is calculated as average g/day and g/kg/day.	pre phase 1
Secondary	Changes from baseline Walking speed to 4 months	Self-selected and maximal walking speed is measured.	Baseline and 4 months follow-up
Secondary	Changes from baseline Stand and reach to 4 months	The ability to stand and reach is tested	Baseline to 4 months follow-up
Secondary	Changes from baseline Walking distance to 4 months	The distance walked during 2- and 6-minutesis tested.	Baseline and 4 months follow-up
Secondary	Changes from baseline Upper body ball throwing to 4 months	The ability to throw a ball, using the upper body is tested.	Baseline to 4 months follow-up
Secondary	Changes from baseline Rising from laying position to 4 months	the ability to rise from laying position is tested.	Baseline to 4 months follow-up
Secondary	Changes from baseline Nutritional status to 4 months	Nutrititional status is estimated by validated questionnaires: the Mini Nutritional Assessment and Eating Validation Scheme. Scores range from 0-30 and 0-3, respectively.	Baseline and 4 months follow-up
Secondary	Changes in Risk of poor protein intake to 4 months	The questionnaire (protein screener) is used to estimate the probability score of having a low protein intake.	Baseline and 4 months