InflammagingNCT03308747
Inflammaging and Muscle Protein Metabolism
A study testing Instantized Whey Protein Isolate in people with Inflammaging and Sarcopenia, run by University of Thessaly at 1 site in Greece.
Trial summary
The development of a low-grade, chronic, systemic inflammation observed in the elderly (inflammaing) has been associated with increased risk for skeletal muscle wasting, strength loss and functional impairments. Read more about this study
- Who is it for?
- Ages 63 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammaging, Sarcopenia
- What is being tested?
- Instantized Whey Protein Isolate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteGreece
- Study dates
- 1 Sep 2017to 30 May 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 63 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Non-smokers.
- BMI ≥18.5 \& BMI ≤ 35 kg/m2.
- Moderately active but with no regular participation in heavy resistance exercise within the last 6 months.
- Absence of chronic disease (i.e. cancer, metabolic, cardiac, or neurological diseases).
- Free and independently living.
Who cannot join
- Organ failure (unstable, renal, respiratory, liver).
- Chronic use of corticosteroid medication.
- Recent use of antibiotics.
- Presence of frailty.
- Body weight variation over the past 6mo > 10% or weight loss of more than 3kg in the last 3 months.
- Use of anti-inflammatory or lipid-lowering medication (i.e., statins).
- Use of medication interacting with muscle metabolism.
Trial locations and contacts
1 site in 1 country.
Greece1 site
Exercise Biochemistry Laboratory, School of Physical Education & Sports Sciences, University of Thessaly
Trikala, 42100
About this study
Official title: Effects of Low-grade Systemic Inflammation on Muscle Protein Synthesis and Breakdown in the Aged Skeletal Muscle.
The development of a low-grade, chronic, systemic inflammation observed in the elderly (inflammaing) has been associated with increased risk for skeletal muscle wasting, strength loss and functional impairments. According to studies performed in animals and cell cultures increased concentrations of pro-inflammatory cytokines such as IL-6 and TNF-α as well as increased levels of hs-CRP lead to elevated protein degradation through proteasome activation and reduced muscle protein synthesis (MPS) via downregulation of the Akt-mTOR signaling pathway. However, evidence regarding the effects of inflammaging on skeletal muscle mass in humans is lacking. Thus, the present study will compare proteasome activation and the protein synthetic response in the fasted and postprandial period between older adults with increased systemic inflammation and their healthy control counterparts.
Read the detailed description
A total number of > 60 male, older adults aged 63-73 years will be initially screened for systemic levels of hs-CRP and IL-6. Of these, 24 individuals that will comply with the study criteria will be allocated to either a High (IL6: ≥ 1.7 pg/ml; hs-CRP: > 1.0 mg/L) (n=12) or a Low (IL6: < 1.7 pg/ml; hs-CRP: < 1.0 mg/L) (n=12) systemic inflammation group. Approximately 2 weeks before the experimental trial, anthropometry, resting metabolic rate (RMR), body composition (with DXA), sarcopenia status, functional capacity and the knee-extension one repetition maximum (1RM) will be assessed in individuals from both groups. In addition, levels of habitual physical activity will be assessed using accelerometry (over a 7-day period) and daily dietary intake will be monitored through 7-day diet recalls in all participants. 1 week before the experimental day an oral glucose tolerance test (OGTT) will be also performed over a 2-hour period, with blood sampling every 15min during the first hour and every 30min during the second hour. The day before the experimental trial, participants will consume 150ml of D2O 70% atom as a bolus. In the experimental day, participants will arrive at the laboratory after an overnight fast and a baseline blood sample and a muscle biopsy from vastus lateralis muscle will be collected. Immediately after, participants will perform 8 sets with 10 repetitions at 80% of 1RM and 2 min rest between each set, on a knee-extension machine. After exercise, they will ingest 0.4 g whey protein isolate/kg body weight as single bolus and then they will remain in a sitting position over a 3-hour period. Blood samples will be collected every 30min during the 3-hour postprandial period while a second muscle biopsy will be obtained at 3h.
- Conditions
- Inflammaging, Sarcopenia
- Being tested
- Instantized Whey Protein Isolate
- Keywords
- Low-grade systemic inflammation, Muscle protein synthesis, Proteasome activation, Anabolic signaling, Aging, Sarcopenia
- Medical subject headings
- Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Instantized Whey Protein IsolateDietary supplement
0,4 g of whey protein isolate/kg body weight will be ingested as a bolus of 250 ml immediately after the resistance exercise bout.
| Study group | Role | What they receive |
|---|---|---|
| High systemic inflammation | Experimental | Individuals assigned in the high systemic inflammation group will be characterized by IL6: ≥ 1.7 pg/ml and hs-CRP: > 2.0 mg/L. Receives: Dietary Supplement: Instantized Whey Protein Isolate |
| Low systemic inflammation | Active comparator | Individuals assigned in the high systemic inflammation group will be characterized by IL6: < 1.7 pg/ml and hs-CRP: < 1.0 mg/L. Receives: Dietary Supplement: Instantized Whey Protein Isolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systemic inflammation
Levels of systemic inflammation will be assessed by measuring serum levels of hs-CRP, IL-6 and TNF-α.
Measured: At baseline.
Change in muscle protein synthesis (MPS)
Using deuterium oxide (D2O) 70% atom administration. Individuals will consume a single bolus of 150ml D20 the day before the clinical trial and muscle biopsy samples, collected before and after the exercise bout and protein ingestion, will be analyzed for isotopic measurement using GC-P-IRMS.
Measured: At baseline and 180 min following protein ingestion.
Change in intracellular signaling proteins in muscle
Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), p70S6K and ribosomal protein S6 (rpS6) will be measure using western blotting.
Measured: At baseline and 180 min following protein ingestion.
Change in proteasome activities in muscle
Chymotrypsin-like (CT-L), caspase-like (C-L) and trypsin-like (T-L) proteasome activities will be assayed with hydrolysis of the fluorogenic peptide LLVY-AMC, LLE-AMC and LSTR-AMC, respectively.
Measured: At baseline and 180 min following protein ingestion.
Change in protein expression level of proteasome subunits
Immunoblot analysis will be used to detect protein expression levels of proteasome (β5, β2 and β1) and immunoproteasome (β5i, β2i and β1i) subunits.
Measured: At baseline and 180 min following protein ingestion.
Secondary outcomes (18)
Resting metabolic rate (RMR)
RMR will be assessed after an overnight fast with participants in a supine position following a 15-min stabilization period by taking 30 consecutive 1-min VO2/CO2 measurements using a portable open-circuit indirect calorimeter with a ventilated hood system following a standard calibration protocol.
Measured: At baseline.
Physical activity
Level of habitual physical activity will be assessed using accelerometry (ActiGraph GT3X-BT accelerometer).
Measured: Over a 7-day period at baseline.
Dietary intake
Daily dietary intake will be assessed using 7-day diet recalls.
Measured: Over a 7-day period at baseline.
Reduced glutathione in blood
Concentration of reduced glutathione will be measured in red blood cells
Measured: At baseline.
Oxidized glutathione in blood
Concentration of oxidized glutathione will be measured in red blood cells
Measured: At baseline.
Protein carbonyls in serum
Concentration of protein carbonyls will be measured in serum.
Measured: At baseline.
Total antioxidant capacity
Total antioxidant capacity will be measured in serum
Measured: At baseline.
Malondialdehyde in serum
Concentration of malondialdehyde will be measured in serum.
Measured: At baseline.
White blood cell count in blood
White blood cell count will be measured in blood.
Measured: At baseline.
Insulin sensitivity
Insulin sensitivity will be assessed through an oral glucose tolerance test (OGTT) which involve ingesting glucose solution (75 g) with 5ml arterialized venous blood samples drawn at baseline and every 15 min during the first hour and every 30 min during the second hour over a 2-hour period.
Measured: At baseline.
Glucose concentration in blood
Glucose concentration will be measured in plasma during the clinical trial.
Measured: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
Insulin concentration in blood
Insulin concentration will be measured in plasma during the clinical trial.
Measured: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
Body composition
Body composition will be measured using a dual-energy x-ray absorptiometry scanner (DEXA).
Measured: At baseline
Body Mass Index (BMI)
Calculated as body mass (kg) divided by the height (m) squared.
Measured: At baseline
Skeletal muscle index
Calculated as an appendicular lean mass (kg) divided by height (m) squared.
Measured: At baseline
Grip strength
Using handgrip dynamometry (left and right arm) in a sitting position.
Measured: At baseline
Functional performance
Functional performance will be assessed using the Short Physical Performance Battery (SPPB).
Measured: At baseline
Lower limb muscle strength
Will be assessed by defining the 1 repetition maximum (1RM) on a knee-extension machine.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start1 Sep 2017
- Primary completion15 Feb 2018
- Study completion30 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InflammagingStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Thessaly
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ioannis G. Fatouros, University of Thessaly
- Investigators
- DIMITRIOS DRAGANIDIS, PhDc, Principal investigator, UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03308747
- Sponsor's protocol ID
- INFLAMMAGING-UTH
- Status last verified
- Oct 2017
- First submitted
- 2 Oct 2017
- Last updated
- 19 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Low-grade Systemic Inflammation on Muscle Protein Synthesis and Breakdown in the Aged Skeletal Muscle.
- ClinicalTrials.gov ID
- NCT03308747
- Acronym / sponsor ID
- INFLAMMAGING-UTH
- Conditions
- Inflammaging, Sarcopenia
- Keywords
- Low-grade systemic inflammation, Muscle protein synthesis, Proteasome activation, Anabolic signaling, Aging, Sarcopenia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of ThessalyUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 15 Feb 2018 (actual)
- Study completion
- 30 May 2018 (actual)
- First posted
- 13 Oct 2017 (actual)
- 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 development of a low-grade, chronic, systemic inflammation observed in the elderly (inflammaing) has been associated with increased risk for skeletal muscle wasting, strength loss and functional impairments. According to studies performed in animals and cell cultures increased concentrations of pro-inflammatory cytokines such as IL-6 and TNF-α as well as increased levels of hs-CRP lead to elevated protein degradation through proteasome activation and reduced muscle protein synthesis (MPS) via downregulation of the Akt-mTOR signaling pathway. However, evidence regarding the effects of inflammaging on skeletal muscle mass in humans is lacking. Thus, the present study will compare proteasome activation and the protein synthetic response in the fasted and postprandial period between older adults with increased systemic inflammation and their healthy control counterparts.
Detailed description
A total number of > 60 male, older adults aged 63-73 years will be initially screened for systemic levels of hs-CRP and IL-6. Of these, 24 individuals that will comply with the study criteria will be allocated to either a High (IL6: ≥ 1.7 pg/ml; hs-CRP: > 1.0 mg/L) (n=12) or a Low (IL6: < 1.7 pg/ml; hs-CRP: < 1.0 mg/L) (n=12) systemic inflammation group. Approximately 2 weeks before the experimental trial, anthropometry, resting metabolic rate (RMR), body composition (with DXA), sarcopenia status, functional capacity and the knee-extension one repetition maximum (1RM) will be assessed in individuals from both groups. In addition, levels of habitual physical activity will be assessed using accelerometry (over a 7-day period) and daily dietary intake will be monitored through 7-day diet recalls in all participants. 1 week before the experimental day an oral glucose tolerance test (OGTT) will be also performed over a 2-hour period, with blood sampling every 15min during the first hour and every 30min during the second hour. The day before the experimental trial, participants will consume 150ml of D2O 70% atom as a bolus. In the experimental day, participants will arrive at the laboratory after an overnight fast and a baseline blood sample and a muscle biopsy from vastus lateralis muscle will be collected. Immediately after, participants will perform 8 sets with 10 repetitions at 80% of 1RM and 2 min rest between each set, on a knee-extension machine. After exercise, they will ingest 0.4 g whey protein isolate/kg body weight as single bolus and then they will remain in a sitting position over a 3-hour period. Blood samples will be collected every 30min during the 3-hour postprandial period while a second muscle biopsy will be obtained at 3h.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High systemic inflammation | Experimental | Dietary Supplement: Instantized Whey Protein IsolateIndividuals assigned in the high systemic inflammation group will be characterized by IL6: ≥ 1.7 pg/ml and hs-CRP: > 2.0 mg/L. |
| Low systemic inflammation | Active comparator | Dietary Supplement: Instantized Whey Protein IsolateIndividuals assigned in the high systemic inflammation group will be characterized by IL6: < 1.7 pg/ml and hs-CRP: < 1.0 mg/L. |
Who may qualify
- Ages
- 63 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Non-smokers.
- BMI ≥18.5 \& BMI ≤ 35 kg/m2.
- Moderately active but with no regular participation in heavy resistance exercise within the last 6 months.
- Absence of chronic disease (i.e. cancer, metabolic, cardiac, or neurological diseases).
- Free and independently living.
Key exclusion criteria (7 listed)
- Organ failure (unstable, renal, respiratory, liver).
- Chronic use of corticosteroid medication.
- Recent use of antibiotics.
- Presence of frailty.
- Body weight variation over the past 6mo > 10% or weight loss of more than 3kg in the last 3 months.
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 |
|---|---|---|
| Instantized Whey Protein Isolate0,4 g of whey protein isolate/kg body weight will be ingested as a bolus of 250 ml immediately after the resistance exercise bout. | Dietary supplement | High systemic inflammation, Low systemic inflammation |
Primary outcome
Systemic inflammation
Time frame: At baseline.
Levels of systemic inflammation will be assessed by measuring serum levels of hs-CRP, IL-6 and TNF-α.
Change in muscle protein synthesis (MPS)
Time frame: At baseline and 180 min following protein ingestion.
Using deuterium oxide (D2O) 70% atom administration. Individuals will consume a single bolus of 150ml D20 the day before the clinical trial and muscle biopsy samples, collected before and after the exercise bout and protein ingestion, will be analyzed for isotopic measurement using GC-P-IRMS.
Change in intracellular signaling proteins in muscle
Time frame: At baseline and 180 min following protein ingestion.
Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), p70S6K and ribosomal protein S6 (rpS6) will be measure using western blotting.
Change in proteasome activities in muscle
Time frame: At baseline and 180 min following protein ingestion.
Chymotrypsin-like (CT-L), caspase-like (C-L) and trypsin-like (T-L) proteasome activities will be assayed with hydrolysis of the fluorogenic peptide LLVY-AMC, LLE-AMC and LSTR-AMC, respectively.
Change in protein expression level of proteasome subunits
Time frame: At baseline and 180 min following protein ingestion.
Immunoblot analysis will be used to detect protein expression levels of proteasome (β5, β2 and β1) and immunoproteasome (β5i, β2i and β1i) subunits.
18 secondary outcomes
Resting metabolic rate (RMR)
Time frame: At baseline.
Physical activity
Time frame: Over a 7-day period at baseline.
Dietary intake
Time frame: Over a 7-day period at baseline.
Reduced glutathione in blood
Time frame: At baseline.
Oxidized glutathione in blood
Time frame: At baseline.
Protein carbonyls in serum
Time frame: At baseline.
Total antioxidant capacity
Time frame: At baseline.
Malondialdehyde in serum
Time frame: At baseline.
White blood cell count in blood
Time frame: At baseline.
Insulin sensitivity
Time frame: At baseline.
Glucose concentration in blood
Time frame: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
Insulin concentration in blood
Time frame: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
Body composition
Time frame: At baseline
Body Mass Index (BMI)
Time frame: At baseline
Skeletal muscle index
Time frame: At baseline
Grip strength
Time frame: At baseline
Functional performance
Time frame: At baseline
Lower limb muscle strength
Time frame: At baseline
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 19 Jul 2018.
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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.
DIMITRIOS DRAGANIDIS, PhDc principal investigator
UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Instantized Whey Protein Isolate in people with Inflammaging and Sarcopenia, run by University of Thessaly at 1 site in Greece.
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 5 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 19 Jul 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 Greece. 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?
Systemic inflammation (time frame: At baseline.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jul 2018.