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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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.

Netherlands1 site
  • Maastricht University

    Maastricht, Limburg, 6200 MD

Other trials in Netherlands

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:

  1. The combined intake of protein and carbohydrates augments post-prandial muscle protein synthesis in the elderly, but not in the young subjects.
  2. 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 groups in NCT01576848
Study groupRoleWhat they receive
GROUP 1 (OLD-PRO)Experimentaltest drink contains intrinsically labeled protein alone
Receives: Dietary Supplement: Protein
GROUP 2 (OLD-PRO/CARB)Experimentaltest drink contains intrinsically labeled protein and carbohydrate
Receives: Dietary Supplement: Protein + carbohydrate
GROUP 3 (YOUNG-PRO)Experimentaltest drink contains intrinsically labeled protein alone
Receives: Dietary Supplement: Protein
GROUP 4 (YOUNG-PRO/CARB)Experimentaltest 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.

  1. 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)
  1. 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

  2. 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

  3. 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

  4. 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.

  1. First posted13 Apr 2012 (estimated)
  2. Study startAug 2011
  3. Primary completionMar 2012
  4. Study completionMar 2012

Resources

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)
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 32069356
  • Kouw 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 26037513
  • Gorissen 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

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.

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