SarcopeniaPRO-CARBNCT01576848
Impact of Carbohydrate Co-ingestion on the Post-prandial Anabolic Response of Protein in Young and Elderly Men
A study testing Protein and Protein + carbohydrate in people with Sarcopenia, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Age related muscle loss (sarcopenia) is assumed to be related to the impaired postprandial muscle protein synthetic response to protein and/or amino acid administration in the elderly vs the young. Co-ingestion of carbohydrate increases post-prandial insulin secretion. Read more about this study
- Who is it for?
- Ages 18 to 85 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sarcopenia
- What is being tested?
- Protein and Protein + carbohydrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2011to Mar 2012
- 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 18 to 85 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males
- Age 70-85 years or Age 18-30 years
- BMI < 30 kg∙m2
Who cannot join
- Diabetes
- HbA1c > 7.0%
- Obesity (BMI > 30 kg/m2)
- Diagnosed impaired renal or liver function
- All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthrosis, arthritis, spasticity/rigidity, all neurological disorders and paralysis).
- Hypertension (according to WHO criteria) (36)
Show all 12Show fewer
- Use of anticoagulants, blood diseases, allergy for lidocain
- Use of NSAIDs and acetylsalicylic acid
- Use of gastric acid inhibitors
- Patients suffering from PKU (Phenylketonuria)
- Participation in any regular exercise program
- Unstable body weight over the last 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Rationale: Age related muscle loss (sarcopenia) is assumed to be related to the impaired postprandial muscle protein synthetic response to protein and/or amino acid administration in the elderly vs the young. Co-ingestion of carbohydrate increases post-prandial insulin secretion. Insulin affects skeletal muscle blood flow and may therefore affect substrate availability and postprandial muscle protein synthesis. However, it is unclear whether the response to the combined intake of protein and carbohydrates is different in elderly compared to young subjects.
Hypothesis: Adding carbohydrate to a bolus of protein represents an effective strategy to overcome the impaired postprandial muscle protein synthesis in the elderly.
Read more
Objective: The primary objective of the study is to investigate whether carbohydrate co-ingestion augments the in vivo postprandial muscle protein synthetic response after protein ingestion and whether this response is different between young and elderly subjects. The secondary objective of the study is to assess the effect of carbohydrate co-ingestion on insulin levels and microvascular perfusion in young and elderly subjects.
Intervention: The intervention consists of a single test day during which the subjects will receive a drink containing 20 gram intrinsically labelled casein with or without 60 gram carbohydrates. In addition, continuous intravenous tracer infusions of labeled amino acids will be administered. During the test day 18 plasma samples and 4 muscle biopsies will be collected over a period of 8½ h. Furthermore, muscle skeletal blood flow will be estimated using sidestream darkfield imaging (SDF) in sublingual position.
Read the detailed description
With human aging, there is a gradual but progressive decline in skeletal muscle tissue, also known as sarcopenia . Sarcopenia is accompanied by a reduced physical performance, the loss of functional capacity, increased risk of falling and increased likelihood of developing chronic metabolic diseases, such as type 2 diabetes and obesity. Eventually this also results in increased hospitalisation and institutionalization of elderly in nursing homes, and high health care costs. Therefore, it is important to investigate approaches to diminish the loss of skeletal muscle mass during aging. To preserve muscle mass, protein intake is important, because it provides the building blocks for muscle tissue: amino acids. Since basal muscle protein synthesis rates do not seem to differ between young and elderly, currently many research groups focus on postprandial muscle protein synthesis. Skeletal muscle protein synthesis has been shown to be highly dependent on protein intake. However, recent data indicate that the muscle protein synthetic response to protein intake is attenuated in the elderly. A blunted postprandial muscle protein synthetic response over a prolonged period might result in diminished muscle protein accretion and could eventually contribute to sarcopenia.
The anabolic response to protein intake appears to be mainly mediated by an elevation of plasma essential amino acids. In addition, ingestion of carbohydrate leads to an attenuation of muscle protein breakdown by virtue of an elevation in plasma insulin, further promoting positive net protein balance. This is mediated by insulin's known action of increasing muscle blood flow and thereby augmenting muscle substrate delivery, which may lead to further stimulation of muscle protein synthesis. It has been shown that there is an insulin resistance with respect to muscle protein anabolism in elderly compared to young subjects during conditions of high plasma amino acid and insulin availability. This suggests that the reduced ability of insulin to augment muscle microvascular perfusion decreases the amino acid stimulus.
In the present study the investigators will assess the effect of a single meal-like amount of intact protein with or without carbohydrates on post-prandial muscle protein synthesis in the elderly (70-85 y) compared to the young (18 - 30 y). Furthermore, the investigators are going to investigate whether the muscle protein synthetic response is associated with an increase in the microvascular perfusion after ingestion of the meal using Sidestream Dark Field (SDF) imaging. SDF measurements will be taken in de oral cavity underneath the tongue, since this area is easily accessible and is representative for microvascular perfusion. To be able to measure the effect of protein ingestion on muscle protein synthesis the investigators will use intrinsically labelled casein. This allows us to determine the true incorporation of amino acids from the ingested, intact casein into the muscle, taken into account the influence of digestion and absorption processes of a whole protein. Intrinsically labelled milk proteins were derived from milk that has been collected from cows that were infused with L-[1-13C] phenylalanine.
The following hypotheses will be investigated:
- The combined intake of protein and carbohydrates augments post-prandial muscle protein synthesis in the elderly, but not in the young subjects.
- The increased insulin production following the combined intake of protein and carbohydrates results in an increased microvascular perfusion that is related to the post-prandial muscle protein synthetic response.
- Conditions
- Sarcopenia
- Being tested
- Protein, Protein + carbohydrate
- Keywords
- muscle metabolism, intrinsically labeled protein, protein synthesis, insulin, perfusion
- Medical subject headings
- Sarcopenia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProteinDietary supplement
Also called Intrinsically labelled casein
Subjects will receive a drink containing 20 gram intrinsically labelled casein.
Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y).
Protein + carbohydrateDietary supplement
Also called Casein plus dextrose monohydrate and maltodextrin
subjects will receive a drink containing 20 gram intrinsically labelled casein plus 60 gram carbohydrates.
Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y).
| Study group | Role | What they receive |
|---|---|---|
| GROUP 1 (OLD-PRO) | Experimental | test drink contains intrinsically labeled protein alone Receives: Dietary Supplement: Protein |
| GROUP 2 (OLD-PRO/CARB) | Experimental | test drink contains intrinsically labeled protein and carbohydrate Receives: Dietary Supplement: Protein + carbohydrate |
| GROUP 3 (YOUNG-PRO) | Experimental | test drink contains intrinsically labeled protein alone Receives: Dietary Supplement: Protein |
| GROUP 4 (YOUNG-PRO/CARB) | Experimental | test drink contains intrinsically labeled protein and carbohydrate Receives: Dietary Supplement: Protein + carbohydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from fasted state in Muscle protein synthesis rate (expressed as Fractional Synthetic Rate, FSR) at different time points postprandial
Measured: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Secondary outcomes (4)
Change from fasted state in Whole body protein balance at different time ponits postprandial
Measured: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Microvascular perfusion at different time points postprandial
Measured: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Digestion kinetics of dietary intrinsically labeled protein at different time points postprandial
Measured: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Absorption kinetics of dietary intrinsically labeled protein at different time points postprandial
Measured: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2012 (estimated)
- Study startAug 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SarcopeniaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Henrike Hamer, Maastricht University Medical Center
- Investigators
- Luc JC van Loon, Prof., Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576848
- Sponsor's protocol ID
- METC 11-3-040
- Acronym
- PRO-CARB
- Status last verified
- Apr 2012
- First submitted
- 9 Aug 2011
- Last updated
- 13 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Gorissen SHM, Trommelen J, Kouw IWK, Holwerda AM, Pennings B, Groen BBL, Wall BT, Churchward-Venne TA, Horstman AMH, Koopman R, Burd NA, Fuchs CJ, Dirks ML, Res PT, Senden JMG, Steijns JMJM, de Groot LCPGM, Verdijk LB, van Loon LJC. Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans. J Nutr. 2020 Aug 1;150(8):2041-2050. doi: 10.1093/jn/nxaa024.
PubMed 32069356Kouw IW, Gorissen SH, Burd NA, Cermak NM, Gijsen AP, van Kranenburg J, van Loon LJ. Postprandial Protein Handling Is Not Impaired in Type 2 Diabetes Patients When Compared With Normoglycemic Controls. J Clin Endocrinol Metab. 2015 Aug;100(8):3103-11. doi: 10.1210/jc.2015-1234. Epub 2015 Jun 2.
PubMed 26037513Gorissen SH, Burd NA, Hamer HM, Gijsen AP, Groen BB, van Loon LJ. Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion. J Clin Endocrinol Metab. 2014 Jun;99(6):2250-8. doi: 10.1210/jc.2013-3970. Epub 2014 Mar 14.
PubMed 24628553
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Carbohydrate Co-ingestion on the Post-prandial Anabolic Response of Protein in Young and Elderly Men
- ClinicalTrials.gov ID
- NCT01576848
- Acronym / sponsor ID
- PRO-CARB / METC 11-3-040
- Conditions
- Sarcopenia
- Keywords
- muscle metabolism, intrinsically labeled protein, protein synthesis, insulin, perfusion
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 13 Apr 2012 (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.
Rationale: Age related muscle loss (sarcopenia) is assumed to be related to the impaired postprandial muscle protein synthetic response to protein and/or amino acid administration in the elderly vs the young. Co-ingestion of carbohydrate increases post-prandial insulin secretion. Insulin affects skeletal muscle blood flow and may therefore affect substrate availability and postprandial muscle protein synthesis. However, it is unclear whether the response to the combined intake of protein and carbohydrates is different in elderly compared to young subjects.
Hypothesis: Adding carbohydrate to a bolus of protein represents an effective strategy to overcome the impaired postprandial muscle protein synthesis in the elderly.
Objective: The primary objective of the study is to investigate whether carbohydrate co-ingestion augments the in vivo postprandial muscle protein synthetic response after protein ingestion and whether this response is different between young and elderly subjects. The secondary objective of the study is to assess the effect of carbohydrate co-ingestion on insulin levels and microvascular perfusion in young and elderly subjects.
Intervention: The intervention consists of a single test day during which the subjects will receive a drink containing 20 gram intrinsically labelled casein with or without 60 gram carbohydrates. In addition, continuous intravenous tracer infusions of labeled amino acids will be administered. During the test day 18 plasma samples and 4 muscle biopsies will be collected over a period of 8½ h. Furthermore, muscle skeletal blood flow will be estimated using sidestream darkfield imaging (SDF) in sublingual position.
Detailed description
With human aging, there is a gradual but progressive decline in skeletal muscle tissue, also known as sarcopenia . Sarcopenia is accompanied by a reduced physical performance, the loss of functional capacity, increased risk of falling and increased likelihood of developing chronic metabolic diseases, such as type 2 diabetes and obesity. Eventually this also results in increased hospitalisation and institutionalization of elderly in nursing homes, and high health care costs. Therefore, it is important to investigate approaches to diminish the loss of skeletal muscle mass during aging. To preserve muscle mass, protein intake is important, because it provides the building blocks for muscle tissue: amino acids. Since basal muscle protein synthesis rates do not seem to differ between young and elderly, currently many research groups focus on postprandial muscle protein synthesis. Skeletal muscle protein synthesis has been shown to be highly dependent on protein intake. However, recent data indicate that the muscle protein synthetic response to protein intake is attenuated in the elderly. A blunted postprandial muscle protein synthetic response over a prolonged period might result in diminished muscle protein accretion and could eventually contribute to sarcopenia.
The anabolic response to protein intake appears to be mainly mediated by an elevation of plasma essential amino acids. In addition, ingestion of carbohydrate leads to an attenuation of muscle protein breakdown by virtue of an elevation in plasma insulin, further promoting positive net protein balance. This is mediated by insulin's known action of increasing muscle blood flow and thereby augmenting muscle substrate delivery, which may lead to further stimulation of muscle protein synthesis. It has been shown that there is an insulin resistance with respect to muscle protein anabolism in elderly compared to young subjects during conditions of high plasma amino acid and insulin availability. This suggests that the reduced ability of insulin to augment muscle microvascular perfusion decreases the amino acid stimulus.
In the present study the investigators will assess the effect of a single meal-like amount of intact protein with or without carbohydrates on post-prandial muscle protein synthesis in the elderly (70-85 y) compared to the young (18 - 30 y). Furthermore, the investigators are going to investigate whether the muscle protein synthetic response is associated with an increase in the microvascular perfusion after ingestion of the meal using Sidestream Dark Field (SDF) imaging. SDF measurements will be taken in de oral cavity underneath the tongue, since this area is easily accessible and is representative for microvascular perfusion. To be able to measure the effect of protein ingestion on muscle protein synthesis the investigators will use intrinsically labelled casein. This allows us to determine the true incorporation of amino acids from the ingested, intact casein into the muscle, taken into account the influence of digestion and absorption processes of a whole protein. Intrinsically labelled milk proteins were derived from milk that has been collected from cows that were infused with L-[1-13C] phenylalanine.
The following hypotheses will be investigated:
- The combined intake of protein and carbohydrates augments post-prandial muscle protein synthesis in the elderly, but not in the young subjects.
- The increased insulin production following the combined intake of protein and carbohydrates results in an increased microvascular perfusion that is related to the post-prandial muscle protein synthetic response.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GROUP 1 (OLD-PRO) | Experimental | Dietary Supplement: Proteintest drink contains intrinsically labeled protein alone |
| GROUP 2 (OLD-PRO/CARB) | Experimental | Dietary Supplement: Protein + carbohydratetest drink contains intrinsically labeled protein and carbohydrate |
| GROUP 3 (YOUNG-PRO) | Experimental | Dietary Supplement: Proteintest drink contains intrinsically labeled protein alone |
| GROUP 4 (YOUNG-PRO/CARB) | Experimental | Dietary Supplement: Protein + carbohydratetest drink contains intrinsically labeled protein and carbohydrate |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males
- Age 70-85 years or Age 18-30 years
- BMI < 30 kg∙m2
Key exclusion criteria (12 listed)
- Diabetes
- HbA1c > 7.0%
- Obesity (BMI > 30 kg/m2)
- Diagnosed impaired renal or liver function
- All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthrosis, arthritis, spasticity/rigidity, all neurological disorders and paralysis).
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 |
|---|---|---|
| ProteinAlso: Intrinsically labelled caseinSubjects will receive a drink containing 20 gram intrinsically labelled casein. Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y). | Dietary supplement | GROUP 1 (OLD-PRO), GROUP 3 (YOUNG-PRO) |
| Protein + carbohydrateAlso: Casein plus dextrose monohydrate and maltodextrinsubjects will receive a drink containing 20 gram intrinsically labelled casein plus 60 gram carbohydrates. Half of the subject are young males (YOUNG)(age between 18 and 35 y) and half of the subjects are elderly males (OLD)(age between 70 and 85 y). | Dietary supplement | GROUP 2 (OLD-PRO/CARB), GROUP 4 (YOUNG-PRO/CARB) |
Primary outcome
Change from fasted state in Muscle protein synthesis rate (expressed as Fractional Synthetic Rate, FSR) at different time points postprandial
Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
4 secondary outcomes
Change from fasted state in Whole body protein balance at different time ponits postprandial
Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Microvascular perfusion at different time points postprandial
Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Digestion kinetics of dietary intrinsically labeled protein at different time points postprandial
Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
Change from fasted state in Absorption kinetics of dietary intrinsically labeled protein at different time points postprandial
Time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours
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 13 Apr 2012.
- Derived from this study: PubMed 32069356Gorissen SHM, Trommelen J, Kouw IWK, Holwerda AM, Pennings B, Groen BBL, Wall BT, Churchward-Venne TA, Horstman AMH, Koopman R, Burd NA, Fuchs CJ, Dirks ML, Res PT, Senden JMG, Steijns JMJM, de Groot LCPGM, Verdijk LB, van Loon LJC. Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans. J Nutr. 2020 Aug 1;150(8):2041-2050. doi: 10.1093/jn/nxaa024.
- Derived from this study: PubMed 26037513Kouw IW, Gorissen SH, Burd NA, Cermak NM, Gijsen AP, van Kranenburg J, van Loon LJ. Postprandial Protein Handling Is Not Impaired in Type 2 Diabetes Patients When Compared With Normoglycemic Controls. J Clin Endocrinol Metab. 2015 Aug;100(8):3103-11. doi: 10.1210/jc.2015-1234. Epub 2015 Jun 2.
- Derived from this study: PubMed 24628553Gorissen SH, Burd NA, Hamer HM, Gijsen AP, Groen BB, van Loon LJ. Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion. J Clin Endocrinol Metab. 2014 Jun;99(6):2250-8. doi: 10.1210/jc.2013-3970. Epub 2014 Mar 14.
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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.
Luc JC van Loon, Prof. principal investigator
Maastricht 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 Protein and Protein + carbohydrate in people with Sarcopenia, run by Maastricht University Medical Center at 1 site in Netherlands.
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 3 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 13 Apr 2012. 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 Netherlands. 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?
Change from fasted state in Muscle protein synthesis rate (expressed as Fractional Synthetic Rate, FSR) at different time points postprandial (time frame: Participants will be followed in a fasted state over 2 hours and in a postprandial state over 5 hours). 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 NCT01576848, which also lists 3 linked publications.
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 13 Apr 2012.