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SarcopeniaIncretinNCT02370745

Characterizing the Incretin Effect of Amino Acids and Defining GLP-1 Role on Skeletal Muscle

A study testing GLP-1, Insulin Actrapid and Oral amino acids in people with Sarcopenia, run by University of Nottingham at 1 site in United Kingdom.

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

This study has two protocols the aims of which are: 1. To identify age-related effects of AA on incretin secretion and whether and to what extent AA exhibit a true incretin effect (gut- mediated increases in plasma insulin) in younger individuals. (Protocol 1) 2. Read more about this study

Who is it for?
Ages 18 to 75 years, men onlyHealthy volunteers can take part
Conditions the study is for
Sarcopenia
What is being tested?
GLP-1, Insulin Actrapid and Oral amino acids
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited Kingdom
Study dates
Nov 2014to Mar 2018
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 75 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • For protocol 1: i. Aged between 18-40 or 65-75 years ii. A body mass index (BMI) >18 and <28 kg/m2
  • For Protocol 2: i. Age 65-75 years ii. A body mass index (BMI) >18 and <28 kg/m2

Who cannot join

  • For protocol 1:
  • A BMI < 18 or > 28 kg·m2 ii. Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt or recent cardiac event iii. Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial) iv. Respiratory disease including pulmonary hypertension, chronic obstructive pulmonary disease (COPD), asthma or an forced expiratory volume in 1 minute (FEV1) less than 1.5 litre.
  • Metabolic disease: hyper and hypo-parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes vi. Active inflammatory bowel or renal disease vii. Malignancy viii. Recent steroid treatment (within 6 month), or hormone replacement therapy ix. Clotting dysfunction x. Musculoskeletal or neurological disorders xi. Family history of early (<55y) death from cardiovascular disease
  • For protocol 2:
  • Same as protocol 1 in addition to:
  • Overt muscle wasting i.e. muscle mass is more than 1 standard deviation below normal muscle or fat-free mass for age.
  • Taking beta-adrenergic blocking agents or non-steroidal anti-inflammatory drugs iii. Known sensitivity to SONOVUE or any other drug used in the study. iv. Subject deemed unsuitable for femoral cannulation at screening visit.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Division of Medical Sciences and Graduate Entry Medicine - School of Medicine - University of Nottingham

    Derby, DE22 3DT

Other trials in United Kingdom

About this study

Official title: Characterizing the Incretin Effect of Amino Acids (AA) and Defining the Effect of GLP-1 on Muscle Microvascular Blood Flow and Muscle Protein and Glucose Metabolism in Older Age.

This study has two protocols the aims of which are:

  1. To identify age-related effects of AA on incretin secretion and whether and to what extent AA exhibit a true incretin effect (gut- mediated increases in plasma insulin) in younger individuals. (Protocol 1)
  2. To define the extra-pancreatic ''novel'', insulin independent effects of glucagon like peptide-1 (GLP-1) on postprandial muscle protein and glucose metabolism and microvascular blood flow. (Protocol 2)
Read the detailed description

Protocol 1:

This will explore the first aim. 8 Healthy younger volunteers will be recruited to under go 3 arms cross over studies. Interventions will include oral and intravenous amino acids, in addition to intravenous GLP-1 and glucose dependent insulinotropic polypeptide (GIP).

8 older subjects also will be recruited for comparison of the response of GI hormones to amino acids oral feed between young and older men.

Therefore the total number will be recruited to perform this protocol is 16.

Post intervention in all visits, measurements will be taken for:

Insulin, Amino acids, GLP-1, GIP, Ghrelin and peptide YY (PYY).

The measurable end points for this protocol are:

  1. Gut hormones levels in response to the 2 methods of AA delivery (I.V and oral)
  2. Differences in gut hormones levels between young and older subjects when AA's are delivered orally

Protocol 2:

This will explore the second aim. 16 healthy older subjects will be recruited and subdivided randomly into two groups to receive either post absorptive or postprandial insulin concentrations with or without GLP-1 at physiological ranges in a cross over fashion . During acute study parameters of muscle glucose and amino acids metabolism will be tested together with muscle microvascular recruitment and macro vascular flow in the tested leg.

The measurable end points for this protocol are:

  1. Muscle Glucose uptake, assessed by measuring 2-deoxyglucose (2-DOG) phosphate in muscle biopsies
  2. Myofibrillar protein synthesis, assessed via muscle biopsy fractional synthesis rate (FSR)
  3. Whole Leg Muscle Protein Synthesis, assessed via Arterial-Venous difference (AV method)
  4. Whole Leg Muscle Protein Breakdown, assessed via AV method
  5. Whole Leg Net Protein Balance, assessed via AV method
  6. Muscle microvascular recruitment, assessed via microvascular contrast bubbles filling and refilling post destruction by ultrasound waves.
Conditions
Sarcopenia
Being tested
GLP-1, Insulin Actrapid, Oral amino acids, GIP, Intravenous amino acids
Keywords
Incretin, GLP-1, Skeletal muscle metabolism, Microvascular recruitment, Amino Acids, Microvascular blood flow
Medical subject headings
Sarcopenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GLP-1Drug

    Also called Incretin

    GLP-1 effects on skeletal muscle glucose and amino acid metabolism and microvascular blood flow will be scrutinised under the specified insulin concentrations. It will also be used to test the effect of intravenous feed on insulin secretion.

  • Insulin ActrapidDrug

    Also called Actrapid

    Skeletal muscle metabolic and microvascular parameters will be tested under specified insulin concentrations with or without GLP-1

  • Oral amino acidsDietary supplement

    Also called mixed EAA

    Oral amino acids containing 15 g of amino acids

  • GIPDrug

    Also called Incretin

    This will be co infused with GLP-1 and intravenous amino acids

  • Intravenous amino acidsDrug

    Also called IV AA

    This will aim to deliver iso equivalent amount to the amino acids administered orally

Study groups in NCT02370745
Study groupRoleWhat they receive
Post absorptive insulin without GLP-1ExperimentalSubjects with receive post absorptive insulin concentrations while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. The intervention in this group is Insulin Actrapid to achieve post absorptive insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L . This will form base line measurement for the next arm which will receive GLP-1 in addition.
Receives: Drug: Insulin Actrapid
Postabsorptive insulin with GLP-1ExperimentalSubjects will receive post absorptive insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm. The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve post absorptive insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
Receives: Drug: GLP-1; Drug: Insulin Actrapid
Postprandial insulin without GLP-1ExperimentalSubjects will receive postprandial insulin concentrations without GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. The intervention in this group is Insulin Actrapid to achieve postprandial insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L . This will form base line measurement for the next arm which will receive GLP-1 in addition
Receives: Drug: Insulin Actrapid
Postprandial insulin with GLP-1ExperimentalSubjects with receive postprandial insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm. The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve postprandial insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
Receives: Drug: GLP-1; Drug: Insulin Actrapid
Oral amino acids-YoungExperimentalGut hormones will be measured post oral drink containing 15 g of amino acids in young persons. This will cross over with the following 2 arms. The intervention here is: 15g of mixed essential amino acid drink.
Receives: Dietary Supplement: Oral amino acids
Intravenous (IV) amino acids- YoungExperimentalGut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids in young persons. The intervention in this group: Intravenous amino acids delivering iso-equivalent amount of 15g mixed essential amino acids
Receives: Drug: Intravenous amino acids
IV amino acids, GLP-1, GIP -YoungExperimentalGut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids, GLP-1, GIP in young persons. The intervention in this group: Intravenous amino acids iso-equivalent to oral 15 g mixed essential amino acids, GLP-1 infusion and GIP infusion
Receives: Drug: GLP-1; Drug: GIP; Drug: Intravenous amino acids
Oral amino acids- OlderExperimentalGut hormones will be measured post oral drink containing 15 g of mixed essential amino acids in older persons. The intervention in this arm: 15 gram of oral mixed essential amino acid drink
Receives: Dietary Supplement: Oral amino acids

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Muscle protein and glucose metabolism

    Assessed from muscle biopsies taken for measurement of protein synthesis and breakdown and glucose uptake.

    Measured: 12 months

Secondary outcomes (4)
  1. Leg Microvascular blood flow

    Assessed via contrast enhanced ultrasound.

    Measured: 12 months

  2. Leg Macrovascular blood flow

    Assessed via ultrasound doppler scans

    Measured: 12 months

  3. Insulin secretion in response to oral and intravenous amino acids to assess their ability to exert incretin effect.

    Assessed via serial blood draws measuring insulin level at baseline and and post intervention.

    Measured: 12 months

  4. Gut hormones secretion in response to amino acids in young and older people

    Assessed via serial blood draws measuring gut hormones at baseline and post intervention.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2015 (estimated)
  2. Study startNov 2014
  3. Primary completionMar 2018
  4. Study completionMar 2018

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
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02370745
Sponsor's protocol ID
G12122013 MSGEM
Acronym
Incretin
Status last verified
Mar 2018
First submitted
10 Nov 2014
Last updated
2 May 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Nilsson M, Holst JJ, Bjorck IM. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr. 2007 Apr;85(4):996-1004. doi: 10.1093/ajcn/85.4.996.

    PubMed 17413098
  • Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003 Feb;89(2):239-48. doi: 10.1079/BJN2002760.

    PubMed 12575908
  • Wilkes EA, Selby AL, Atherton PJ, Patel R, Rankin D, Smith K, Rennie MJ. Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia. Am J Clin Nutr. 2009 Nov;90(5):1343-50. doi: 10.3945/ajcn.2009.27543. Epub 2009 Sep 9.

    PubMed 19740975
  • Sjoberg KA, Holst JJ, Rattigan S, Richter EA, Kiens B. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle. Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E355-62. doi: 10.1152/ajpendo.00283.2013. Epub 2013 Dec 3.

    PubMed 24302010
  • Chai W, Dong Z, Wang N, Wang W, Tao L, Cao W, Liu Z. Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes. 2012 Apr;61(4):888-96. doi: 10.2337/db11-1073. Epub 2012 Feb 22.

    PubMed 22357961
  • Abdulla H, Phillips B, Wilkinson D, Gates A, Limb M, Jandova T, Bass J, Lewis J, Williams J, Smith K, Idris I, Atherton P. Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men. J Clin Endocrinol Metab. 2023 Mar 10;108(4):971-978. doi: 10.1210/clinem/dgac613.

    PubMed 36260533

Questions about this trial

What is this clinical trial studying?

A study testing GLP-1, Insulin Actrapid and Oral amino acids in people with Sarcopenia, run by University of Nottingham at 1 site in United Kingdom.

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 7 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 2 May 2018. 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 United Kingdom. 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?

Muscle protein and glucose metabolism (time frame: 12 months). 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 NCT02370745, which also lists 6 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 2 May 2018; AzTrials last refreshed its copy on 8 Nov 2026.

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