Clinical trial NCT03197402: Leucine-enriched Nutraceutical and Attenuating Muscle Loss
Official title: Efficacy of a High Quality Protein Leucine-enriched Nutraceutical in Attenuating Inactivity- and Hypo-energetic Diet-induced Muscle Loss in Older Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Loss
Keywords: Leucine
Protein
Supplementation
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2017-06-23
Enrollment: 20
Sex: FEMALE
Minimum age (years): 70
Maximum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel group design (with repeated measurements within each group)
Primary purpose: TREATMENT

Brief summary: This leucine-enriched protein gummy (as a gummy bar/slab) will be studied to address age-related loss of muscle mass and strength/function in older persons. The product is small volume (approximately 35 g per serve) and low energy (approximately 100 kcal per serve). It is easy to chew and swallow with the consistency of a firm Jello. In addition, it contains an effective dose of leucine in a high-quality protein matrix consisting of milk proteins. Understanding the efficacy of this product on changes in levels of blood amino acids and the molecular signaling required to enhance muscle growth will provide helpful insight for the suggestion of supplemental use.

Detailed description: General experimental design:

Pre-testing will require participants to become familiarized with performing maximal voluntary isometric contractions, as well as touring the laboratory facilities. Participants will be asked to complete dietary records for three days to determine habitual caloric intake. The experimental trial will be conducted in three phases. A baseline run-in phase (Phase 1) during which participants will consume a diet matching their estimated energy requirement to put them in a weight-stable phase. Energy requirements will be estimated using the Harris Benedict equation using an appropriate physical activity factor based on interview responses to a standard activity questionnaire. Participants will then be assigned to either the comparator group (n=10) or leucine-enriched protein food group (n=10). For the subsequent 10d (Phase 2), participants will undergo a period of step reduction (\< 1000 steps.d-1) whilst in a 500 kcal.d-1 deficit that will be adjusted for the reduced physical activity due to the step reduction. The reason for inducing an energy deficit is to mimic a situation where older individuals will be both physically inactive and 'undernourished', such as during home-bound periods of sickness or while in hospital. After completing Phase 2, participants will then return to their normal step count (from measured habitual steps pre-intervention) under energy balanced conditions for 10d that will serve as a recovery phase, Phase 3. We will complete assessments of body composition, leg lean mass, maximal voluntary isometric strength, measures of physical performance, and rate of force development will be made. Skeletal muscle biopsies will be obtained for biochemical analysis. At these time points, maximal voluntary isometric force, maximal leg press strength, a battery of physical performance measures and body composition will once again be obtained.

Eligibility criteria: Inclusion Criteria:

* Females between 70 and 75 years of age (a narrow age range improved homogeneity of the sample for this proof-of-concept trial) with a body mass index (BMI) between 27 and 35, and muscle mass 1 standard deviation below that of sex- and ethnicity-matched 30 year olds (note: this has been called 'stage 1 sarcopenia' or 'pre-sarcopenia') will be recruited. In addition, participants will be non-smokers and generally healthy per responses to a standard health screening questionnaire.

Exclusion Criteria:

* Participants who have any one of the following conditions will be excluded:

  * diabetes mellitus
  * cardiovascular disease
  * renal disease
  * gastrointestinal disease
  * musculoskeletal injuries
  * hormone replacement therapy
  * significant weight loss in the 3-month period prior to the study
  * vegan diet
  * dairy protein allergy
  * use of medications known to interfere with muscle metabolism. For example, chronically taking any analgesic or anti-inflammatory drugs(s), prescription or non-prescription
  * a history of neuromuscular problems or muscle and/or bone wasting diseases
  * any acute or chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, insulin- or non-insulin dependent diabetes or other metabolic disorders-all ascertained through medical history screening questionnaires
  * use medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications)

Primary outcomes:
measure: Change from baseline molecular signalling
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Change from baseline lean body mass
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Exercise Metabolism Research Laboratory, McMaster Univeristy
state: Ontario
city: Hamilton
country: Canada
facility: Ivor Wynne Centre A103, McMaster University
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Stuart M Phillips, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly hospitalized patients: a prospective study. JAMA. 1999 Jun 2;281(21):2013-9. doi: 10.1001/jama.281.21.2013.