Clinical trial NCT03649698: Exercise and Nutrition for Healthy AgeiNg
Official title: Exercise and Nutrition for Healthy AgeiNg: Anabolic Interventions for Older People With (Pre)Sarcopenia to Improve Physical Functioning, Muscle Mass and Muscle Strength and to Understand the Underlying Mechanisms of Action.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sarcopenia
Keywords: Sarcopenia
Nutrition
Protein
Vitamin D
Exercise
Older people
Frailty
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: VISTA-Life
name: Nestle Health Science
First posted: 2018-08-28
Enrollment: 180
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this randomized placebo-controlled 5-arm clinical trial is to evaluate the effect of combined anabolic interventions compared to single or placebo interventions on physical performance in community-dwelling (pre)sarcopenic elderly (≥ 65 years) and to determine the underlying mechanisms of action. Important secondary outcome measures are muscle mass, muscle strength, compliance to the interventions (exercise program, protein and omega-3 supplementation) and functional, cognitive and nutritional status.

Detailed description: The aim of this randomized 5-arm clinical trial is to evaluate the effect of combined anabolic interventions compared to single or placebo interventions on physical performance in community-dwelling (pre)sarcopenic elderly (≥ 65 years) living in Belgium. Physical performance will be evaluated using the Short Physical Performance Battery (SPPB). Muscle mass will be measured using a dual energy x-ray absorptiometry (DXA) and/or bioelectrical impedance analysis (BIA). Muscle strength will be measured by the Biodex (knee-extensor and knee-flexor) and a 1 hand-held dynamometer. The trial will also determine the underlying mechanisms of action using blood measures (such as markers of inflammation and sarcopenia) and muscle biomarkers. Important secondary outcome measures are compliance to the exercise program and to the protein and omega-3 supplementation, as well as functional, cognitive and nutritional status and the patients report on benefits and adverse events.

The study consists of four parts. Part I is the screening phase, which starts from the moment the participant has signed the informed consent until the start of the preparations of the study. During the screening, participants will be assessed for study eligibility by the study coordinator and contributors. If the participant is eligible, he or she will be randomly assigned into 1 of 5 intervention groups: Group 1: Exercise intervention; Group 2: Protein supplement; Group 3: Exercise intervention + protein supplement; Group 4: Exercise + Protein supplement + omega-3 supplement; Group 5: No intervention.

Part II is the preparation phase, in which the participants starts some of the interventions before the start of the study to familiarize patients with e.g. the intake of a protein supplement. All the participants will take an oral vitamin D supplement (800 IU cholecalciferol) from 4 weeks before the start of the intervention if their vitamin D level is above 20 nmol/L. Patients with a vitamin D level \< 20 nmol/L will receive repletion therapy. A trial diary will be completed by all participants to record PA, falls and intake of protein/omega3/placebo and vitamin D products. Participants in the exercise intervention (group 1, 3 and 4) will be invited to an information session where the Otago Exercise Program (OEP) will be explained and practiced. With respect to the protein supplementation, participants will receive an individually adapted protein supplement to achieve the recommended total daily intake of 1.5 g protein/kg. This will be realized by adding an individualized amount (g) of protein powder during breakfast, lunch, dinner or snack between, before or after meals, based on the subjects' food intake assessed by a food diary. The protein powder is commercially available and consists of 4.5g protein/ 5g powder. The participants in group 2, 3 and 4 will start taking the protein supplement or matched placebo 5 days before the start of the intervention. Four weeks before the start of the intervention, the participants of group 4 will start with the intake of omega-3 (1 capsule providing in total 500 mg eicosapentanoic acid (EPA) and 450 mg docosahexaenoic acid (DHA)) or matched placebo. Placebo will be provided for the participants who are not given a protein and/or omega-3 supplement. Participants are blinded to the nutritional interventions.

The third part of the study, the intervention period, takes 12 weeks. During this period, there are 8 contact moments (at baseline, week 1, week 2, week 4, week 6, week 8, week 10 and week 12). All the participants continue with the vitamin D supplementation. Participants in the exercise intervention (group 1, 3 and 4) will perform the optimized and personally adapted OEP and will also follow a walking plan. The strength exercises of the OEP are personalised based on the individual's 1 repetition maximum. Balance exercises of the OEP are personalised based on improvements on MiniBESTest scores during the intervention period. The nutritional intervention groups (protein supplementation: group 2, 3 and 4 and omega-3 supplementation: group 4) continue with the protein and/or omega-3 supplements until the last visit of the intervention period.

Part IV is the follow-up period, after the intervention. This phase takes 12 weeks and exists of 2 telephone contacts and 2 contact moments. All the participants continue the vitamin D supplementation until the last visit of the follow-up. The exercise intervention group (group 1, 3 and 4) may continue the OEP, but no personal encouragement will be given during this period. No protein and/ or omega-3 supplements will be given during the follow-up.

Several outcomes will be measured during the contact moments of the intervention period and follow-up period (part III and part IV). This will be done by questionnaires about nutritional status, fall history and use of health care (from baseline until end of follow-up), and evaluation of functional and cognitive status. Blood, urine and muscle samples will be taken. The physical activity will be measured by wearing a movement tracker. All participants will wear a movement tracker 5 days before the intervention period and during the first two weeks of the intervention period and last two weeks of the intervention period, and during the last 2 weeks of the follow-up period. Participants who receive an exercise intervention (group 1, 3 and 4) will be encouraged to wear the movement tracker during the complete intervention period. The participants will complete a four-day food diary throughout the trial at week 1, week 6, week 12 and week 24. The participants will be asked for compliance during the preparation period and intervention period and their fall history which can be monitored by using diaries during the intervention period and the follow-up period.

Addendum 27-07-2021: starting from 01-2021 a substudy was initiated in which participants of ENHANce, who agreed for participation in this substudy, collect stool samples at baseline, week 4, week 8 and week 12 of the intervention. This will allow to observe possible changes in gut microbiota composition and intestinal inflammation.

Eligibility criteria: Inclusion Criteria:

1. Male or female persons with (pre)sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP): reduced muscle mass without (presarcopenia) or with (sarcopenia) reduced walking speed (≤ 0.8m/s) or muscle strength OR probable, confirmed or severe sarcopenia according to EWGSOP 2.
2. 65 years or older;
3. Community-dwelling elderly or assisted living;
4. In case of one or more positive answer(s) on the health screen for exercise, subjects need approval of their general practitioner to participate in this randomized controlled trial (RCT).

   * Uncontrolled or unstable health problems
   * Uncontrolled pain or feeling unwell the day of the exercise
   * Recently diagnosed cardiovascular events
   * systolic blood pressure (SBP) ≥ 180 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg
   * Resting tachycardia \> 100 bpm
   * Uncontrolled atrial or ventricular arrhythmias
   * Unstable or acute heart failure
   * Lasting, increased pain following a previous session
   * Suspected acute injury
   * Recent injurious fall without medical assessment
   * Severe breathlessness or dizziness
   * Uncontrolled pulmonary problems
   * Rheumatoid arthritis flare up or acute systemic illness/infection
   * Unexplained lethargy

Exclusion Criteria:

1. Impairments/diseases that impose problems to participation in the study;
2. Allergy to milk or soy or peanut;
3. Mini-Mental State Examination (MMSE) \< 21;
4. Terminal illness (prognosis \< 6 months);
5. Persons who followed a physical training program in the last 6 months (twice or more/week);
6. Persons with a daily intake of \> 1.5 g protein/kg body weight (BW)/day;
7. Diagnosis of severe kidney disease (GFR \< 30 ml/min) or diabetes mellitus;
8. Unable to communicate in Dutch, English or French.

Primary outcomes:
measure: Change in physical functioning
timeFrame: Measured at baseline, week 12 and week 24.
measure: Percentage of participants with change in physical functioning
timeFrame: Measured at baseline, week 12 and week 24.
Secondary outcomes:
measure: Change in muscle mass (after intervention-baseline)
timeFrame: Measured at screening, week 12 and week 24 with DXA or when screening is 6 weeks prior to baseline, DXA will also be performed at baseline. At screening, baseline, week 12 and week 24 with BIA.
measure: Change in muscle strength (after intervention-baseline)
timeFrame: Hand grip measured at screening, baseline, week 12 and week 24. Biodex measured at baseline, week 12 and week 24.
measure: Compliance to the exercise intervention, subjective
timeFrame: baseline until week 12
measure: Compliance to the exercise intervention, objective
timeFrame: baseline until week 12
measure: Compliance to the exercise intervention, subjective, detailed
timeFrame: baseline until week 12
measure: Compliance to the protein supplementation, objective
timeFrame: Urine samples at baseline, week 1, 2, 4, 6, 8, 10, 12, 24.
measure: Compliance to the protein supplementation, subjective
timeFrame: Urine samples at baseline, week 1, 2, 4, 6, 8, 10, 12, 24.
measure: Compliance to the protein supplementation objective
timeFrame: Urine samples at baseline, week 1, 2, 4, 6, 8, 10, 12, 24.
measure: Compliance to the omega-3 supplementation, subjective
timeFrame: baseline, week 12 and week 24.
measure: Compliance to the omega-3 supplementation, objective
timeFrame: baseline, week 12 and week 24.
measure: Functional status: frailty
timeFrame: baseline, week 12 and 24
measure: Functional status: activities of daily living
timeFrame: baseline, week 12 and 24
measure: Functional status: balance
timeFrame: baseline, week 12 and 24
measure: Functional status: change in physical activity
timeFrame: baseline, week 12 and 24
measure: Functional status: health-related quality of life
timeFrame: baseline, week 12 and 24
measure: Functional status: falls
timeFrame: baseline, week 12 and 24
measure: Cognitive status: immediate and delayed memory, attention, language and visuospatial skills
timeFrame: baseline, week 12 and 24
measure: Cognitive status: inhibition
timeFrame: baseline, week 12 and 24
measure: Cognitive status
timeFrame: baseline, week 12 and 24
measure: Nutritional status: malnutrition
timeFrame: at baseline (preparation for food diary), week 6, week 12 and week 24
measure: Nutritional status: nutrient intake
timeFrame: at baseline (preparation for food diary), week 6, week 12 and week 24
measure: Patient reported benefits and adverse effects
timeFrame: week 1, 4, 8, 12, 16, 20, 22, 24.
measure: Change in C reactive protein (CRP)
timeFrame: baseline, week 1, 4, 12 and 24
measure: Change in hemoglobin
timeFrame: baseline, week 12 and week 24
measure: Change in creatinine
timeFrame: baseline, week 12 and week 24
measure: Change in urea
timeFrame: baseline, week 12 and week 24
measure: Change in serum albumin
timeFrame: baseline, week 12 and week 24
measure: Change in glucose
timeFrame: baseline, week 12 and week 24
measure: Change in cholesterol (HDL, LDL, total, Triglycerides)
timeFrame: baseline, week 12 and week 24
measure: Change in insulin
timeFrame: baseline, week 12 and week 24
measure: Change in insulin like growth factor 1 (IGF-1)
timeFrame: baseline, week 12 and week 24
measure: Change in 25-hydroxy-vitamin D
timeFrame: baseline, week 12 and week 24
measure: Change in creatinine kinase
timeFrame: baseline, week 12 and week 24
measure: Change in indoxyl sulfate
timeFrame: baseline, week 12 and week 24
measure: Change in interleukin 6 (IL-6)
timeFrame: baseline, week 12 and week 24
measure: Change in IL-1b
timeFrame: baseline, week 12 and week 24
measure: Change in tumor necrosis factor alpha (TNF-alpha)
timeFrame: baseline, week 12 and week 24
measure: Change in myostatin
timeFrame: baseline, week 12 and week 24
measure: Change in activin A
timeFrame: baseline, week 12 and week 24
measure: Change in markers of muscle wasting
timeFrame: baseline, week 12
measure: Change in markers of muscle regeneration
timeFrame: baseline, week 12
measure: Change in muscle histology
timeFrame: baseline, week 12
measure: Change in composition of gut microbiota
timeFrame: baseline, week 4, week 8, week 12
measure: Change in markers of intestinal inflammation
timeFrame: baseline, week 4, week 8, week 12
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Gerontology and Geriatrics, Department of Public Health and primary care KU Leuven
name: Evelien Gielen, Prof MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dedeyne L, Dupont J, Koppo K, Verschueren S, Tournoy J, Gielen E. Exercise and Nutrition for Healthy AgeiNg (ENHANce) project - effects and mechanisms of action of combined anabolic interventions to improve physical functioning in sarcopenic older adults: study protocol of a triple blinded, randomized controlled trial. BMC Geriatr. 2020 Dec 10;20(1):532. doi: 10.1186/s12877-020-01900-5.