AgingNCT02371278
Leucine Co-ingestion and Myofibrillar Protein Synthesis in Older Adults
A study testing Leucine in people with Aging and Sarcopenia, run by McMaster University at 1 site in Canada.
Trial summary
The loss of muscle mass with aging is associated with a dysregulation of muscle protein synthesis (MPS) that is generally characterized by a suppressed MPS response to protein ingestion. Read more about this study
- Who is it for?
- Ages 65 to 85 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Aging, Sarcopenia
- What is being tested?
- Leucine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- May 2015to Oct 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 85 years
- Men only
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Body mass index (BMI) between 20-35 kg/m2
- Non-smokers
Who cannot join
- Diabetes mellitus, prediabetes and the metabolic syndrome
- Cardiovascular disease
- Neuromuscular problems or muscle wasting diseases
- Renal disease
- Gastrointestinal disease
- Musculoskeletal conditions such as rheumatoid arthritis or osteoarthritis
Show all 12Show fewer
- Infectious disease
- Cancer
- Significant body mass loss in the 1 month period prior to the study
- Vegetarianism
- Use of medications known to interfere with muscle metabolism (i.e. beta-blockers, high dose non-steroidal anti-inflammatory drugs, corticosteroids, hormone replacement therapy, antiarrhythmic drugs, warfarin, prescription strength acne medications, oral hypoglycaemic agents and insulin)
- Regular resistance training or daily step counts >9,000 or <3,500
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Leucine Co-ingestion With Mixed Meals on Integrative Myofibrillar Protein Synthesis in Older Adults
The loss of muscle mass with aging is associated with a dysregulation of muscle protein synthesis (MPS) that is generally characterized by a suppressed MPS response to protein ingestion. This 'anabolic resistance' to protein feeding can be overcome with the ingestion of larger protein servings (~0.4g/kg/meal, equivalent to ~ 30 - 40g/meal); however, older adults would likely find it challenging to consume such quantities of protein on a per meal basis.
The amino acid leucine has a unique role as a key 'activator' of MPS. Some research shows that increasing the leucine content of a suboptimal dose of a protein supplement can enhance the MPS response in older adults. However it is currently unknown whether the co-ingestion of leucine with normal, mixed meals can increase MPS. Furthermore, it has been suggested that leucine supplementation may only benefit older adults consuming suboptimal daily protein intakes. Therefore, the purpose of the current study is to examine the impact of leucine co-ingestion with mixed macronutrient meals on the myofibrillar protein synthetic response in older men consuming daily protein intakes at or below the current recommendations. A further objective is to determine whether the myofibrillar protein synthetic response to a session of resistance exercise is enhanced by leucine supplementation with meals. The investigators hypothesize that, in both the exercised and non-exercised condition, leucine co-ingestion at meals will enhance integrative myofibrillar protein synthesis in older adults consuming lower daily protein intakes, but will not augment MPS in those consuming higher daily protein. The investigators further hypothesize that the influence of leucine supplementation on MPS will be greater in the exercise condition than the non-exercise condition.
Read the detailed description
At baseline, participants will be asked to wear a pedometer and to complete a physical activity and a weighed food record for 3 days. Resting energy expenditure (indirect calorimetry), body weight and body composition (DEXA) will be assessed in the fasted state. A strength test will be conducted to determine 1 repetition maximum (1-RM) and the maximum load that each participant can lift for 15 - 24 repetitions using a seated leg extension machine. Participants will then be randomized to one of two groups matched for age, activity level and BMI: higher (1.2 g/kg/d) or lower daily protein (0.8 g/kg/d). Participants will then commence a 9 day controlled diet (day -3 to 6) designed to meet energy requirements for weight maintenance and to provide a daily protein intake according to each participant's group allocation (i.e. 0.8 or 1.2 g/kg/d).
All participants will be provided with flavored, supplemental beverages (Infinit Nutrition, Windsor, Ontario) and will be instructed to consume one beverage half way through each meal from day 0 - 5. Individual servings of the supplement will be packaged into a ziplocked pouch by Infinit Nutrition in power form. Participants will be required to add water to the power at home. During day 0 - 2 (unsupplemented period) the beverage will be a placebo (maltodextrin and sucrose), and during day 3 - 5 (leucine supplementation period) the beverage will contain crystalline leucine (5 g) with sucrose for flavour. The beverages will be provided in a single-blind manner, energy-matched and will be similar in odour, color, and taste. Participants will also be blinded to their group allocation.
Aminoacidemia, insulinemia and glycaemia will be determined in response to breakfast, lunch and dinner ingestion during the unsupplemented (day 2) and leucine supplemented (day 5) periods. During each of these blood sampling trials blood samples will be obtained immediately before and 20, 40, 60, 90, 120, 180, 240 min following the ingestion of each meal (total of 25 x 4ml blood samples per participant per trial).
Integrative MPS will be measured in the exercised and non-exercised leg over the unsupplemented (day 0 - 3) period and leucine supplemented (day 3 - 6) period using orally ingested deuterated water (D20) and muscle biopsies obtained from the vastus lateralis on days 0, 3 and 6. Participants will report to the laboratory in the fasted state on day 0 and, following a muscle biopsy from the vastus lateralis and saliva sample, participants will consume a single 100 ml oral bolus of D20 at approximately 0900. Immediately following the D20 bolus participants will perform a bout of unilateral leg extension exercise (3 sets to volitional failure at the maximum load they can lift for 15-24 repetitions (~40-50% 1-RM)). On day 3 participants will perform an identical resistance exercise session with the exception that repetitions will be clamped at the number achieved on day 0. Following both exercise sessions participants will consume their individualized breakfast (with the placebo beverage on day 0 and with the leucine beverage on day 3) in the laboratory before returning home. Bilateral muscle biopsies will be obtained prior to the exercise on day 3 (end of unsupplemented period) and on day 6 (end of leucine supplemented period). Total body water deuterium enrichment can be used as a surrogate for plasma alanine labelling and will be determined from saliva swabs collected by the participant every morning at 0900. Participants will be instructed to not eat or drink anything for 30 min before saliva sampling and samples will be stored in the participant's freezer before their next visit to the laboratory.
- Conditions
- Aging, Sarcopenia
- Being tested
- Leucine, Placebo
- Keywords
- Leucine, Protein, Diet, Muscle protein synthesis
- Medical subject headings
- Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeucineDietary supplement
5 g leucine with sucrose and maltodextrin
PlaceboDietary supplement
5 g glycine with sucrose and maltodextrin
| Study group | Role | What they receive |
|---|---|---|
| Higher daily protein | Other | Diets will provide protein intakes of 1.2 g/kg/d.
Placebo with meals for 3 days, and leucine with meals for 3 days. Receives: Dietary Supplement: Leucine; Dietary Supplement: Placebo |
| Lower daily protein | Other | Diets will provide protein intakes of 0.8 g/kg/d.
Placebo with meals for 3 days, and leucine with meals for 3 days. Receives: Dietary Supplement: Leucine; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myofibrillar protein fractional synthetic rate
The incorporation of a stable isotope (deuterium) into muscle tissue will allow for the determination of fractional synthetic rate, which is indicative of muscle protein synthesis.
Measured: 3 days
Secondary outcomes (3)
Aminoacidemia in response to daily meals with and without leucine supplementation
Measured: 3 days
Glycaemia in response to daily meals with and without leucine supplementation
Measured: 3 days
Insulinemia in response to daily meals with and without leucine supplementation
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Stuart M. Phillips, McMaster University
- Investigators
- Stuart M Phillips, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02371278
- Sponsor's protocol ID
- LEU-MEALS-2015
- Status last verified
- Mar 2016
- First submitted
- 13 Feb 2015
- Last updated
- 16 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM. Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr. 2016 Dec;104(6):1594-1606. doi: 10.3945/ajcn.116.136424. Epub 2016 Nov 9.
PubMed 27935521
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Leucine Co-ingestion With Mixed Meals on Integrative Myofibrillar Protein Synthesis in Older Adults
- ClinicalTrials.gov ID
- NCT02371278
- Acronym / sponsor ID
- LEU-MEALS-2015
- Conditions
- Aging, Sarcopenia
- Keywords
- Leucine, Protein, Diet, Muscle protein synthesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- May 2015
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The loss of muscle mass with aging is associated with a dysregulation of muscle protein synthesis (MPS) that is generally characterized by a suppressed MPS response to protein ingestion. This 'anabolic resistance' to protein feeding can be overcome with the ingestion of larger protein servings (~0.4g/kg/meal, equivalent to ~ 30 - 40g/meal); however, older adults would likely find it challenging to consume such quantities of protein on a per meal basis.
The amino acid leucine has a unique role as a key 'activator' of MPS. Some research shows that increasing the leucine content of a suboptimal dose of a protein supplement can enhance the MPS response in older adults. However it is currently unknown whether the co-ingestion of leucine with normal, mixed meals can increase MPS. Furthermore, it has been suggested that leucine supplementation may only benefit older adults consuming suboptimal daily protein intakes. Therefore, the purpose of the current study is to examine the impact of leucine co-ingestion with mixed macronutrient meals on the myofibrillar protein synthetic response in older men consuming daily protein intakes at or below the current recommendations. A further objective is to determine whether the myofibrillar protein synthetic response to a session of resistance exercise is enhanced by leucine supplementation with meals. The investigators hypothesize that, in both the exercised and non-exercised condition, leucine co-ingestion at meals will enhance integrative myofibrillar protein synthesis in older adults consuming lower daily protein intakes, but will not augment MPS in those consuming higher daily protein. The investigators further hypothesize that the influence of leucine supplementation on MPS will be greater in the exercise condition than the non-exercise condition.
Detailed description
At baseline, participants will be asked to wear a pedometer and to complete a physical activity and a weighed food record for 3 days. Resting energy expenditure (indirect calorimetry), body weight and body composition (DEXA) will be assessed in the fasted state. A strength test will be conducted to determine 1 repetition maximum (1-RM) and the maximum load that each participant can lift for 15 - 24 repetitions using a seated leg extension machine. Participants will then be randomized to one of two groups matched for age, activity level and BMI: higher (1.2 g/kg/d) or lower daily protein (0.8 g/kg/d). Participants will then commence a 9 day controlled diet (day -3 to 6) designed to meet energy requirements for weight maintenance and to provide a daily protein intake according to each participant's group allocation (i.e. 0.8 or 1.2 g/kg/d).
All participants will be provided with flavored, supplemental beverages (Infinit Nutrition, Windsor, Ontario) and will be instructed to consume one beverage half way through each meal from day 0 - 5. Individual servings of the supplement will be packaged into a ziplocked pouch by Infinit Nutrition in power form. Participants will be required to add water to the power at home. During day 0 - 2 (unsupplemented period) the beverage will be a placebo (maltodextrin and sucrose), and during day 3 - 5 (leucine supplementation period) the beverage will contain crystalline leucine (5 g) with sucrose for flavour. The beverages will be provided in a single-blind manner, energy-matched and will be similar in odour, color, and taste. Participants will also be blinded to their group allocation.
Aminoacidemia, insulinemia and glycaemia will be determined in response to breakfast, lunch and dinner ingestion during the unsupplemented (day 2) and leucine supplemented (day 5) periods. During each of these blood sampling trials blood samples will be obtained immediately before and 20, 40, 60, 90, 120, 180, 240 min following the ingestion of each meal (total of 25 x 4ml blood samples per participant per trial).
Integrative MPS will be measured in the exercised and non-exercised leg over the unsupplemented (day 0 - 3) period and leucine supplemented (day 3 - 6) period using orally ingested deuterated water (D20) and muscle biopsies obtained from the vastus lateralis on days 0, 3 and 6. Participants will report to the laboratory in the fasted state on day 0 and, following a muscle biopsy from the vastus lateralis and saliva sample, participants will consume a single 100 ml oral bolus of D20 at approximately 0900. Immediately following the D20 bolus participants will perform a bout of unilateral leg extension exercise (3 sets to volitional failure at the maximum load they can lift for 15-24 repetitions (~40-50% 1-RM)). On day 3 participants will perform an identical resistance exercise session with the exception that repetitions will be clamped at the number achieved on day 0. Following both exercise sessions participants will consume their individualized breakfast (with the placebo beverage on day 0 and with the leucine beverage on day 3) in the laboratory before returning home. Bilateral muscle biopsies will be obtained prior to the exercise on day 3 (end of unsupplemented period) and on day 6 (end of leucine supplemented period). Total body water deuterium enrichment can be used as a surrogate for plasma alanine labelling and will be determined from saliva swabs collected by the participant every morning at 0900. Participants will be instructed to not eat or drink anything for 30 min before saliva sampling and samples will be stored in the participant's freezer before their next visit to the laboratory.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Higher daily protein | Other | Dietary Supplement: Leucine, Dietary Supplement: PlaceboDiets will provide protein intakes of 1.2 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days. |
| Lower daily protein | Other | Dietary Supplement: Leucine, Dietary Supplement: PlaceboDiets will provide protein intakes of 0.8 g/kg/d. Placebo with meals for 3 days, and leucine with meals for 3 days. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Body mass index (BMI) between 20-35 kg/m2
- Non-smokers
Key exclusion criteria (12 listed)
- Diabetes mellitus, prediabetes and the metabolic syndrome
- Cardiovascular disease
- Neuromuscular problems or muscle wasting diseases
- Renal disease
- Gastrointestinal disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leucine5 g leucine with sucrose and maltodextrin | Dietary supplement | Higher daily protein, Lower daily protein |
| Placebo5 g glycine with sucrose and maltodextrin | Dietary supplement | Higher daily protein, Lower daily protein |
Primary outcome
Myofibrillar protein fractional synthetic rate
Time frame: 3 days
The incorporation of a stable isotope (deuterium) into muscle tissue will allow for the determination of fractional synthetic rate, which is indicative of muscle protein synthesis.
3 secondary outcomes
Aminoacidemia in response to daily meals with and without leucine supplementation
Time frame: 3 days
Glycaemia in response to daily meals with and without leucine supplementation
Time frame: 3 days
Insulinemia in response to daily meals with and without leucine supplementation
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2016.
- Derived from this study: PubMed 27935521Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM. Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr. 2016 Dec;104(6):1594-1606. doi: 10.3945/ajcn.116.136424. Epub 2016 Nov 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart M Phillips, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Leucine in people with Aging and Sarcopenia, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myofibrillar protein fractional synthetic rate (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02371278, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2016.