Inflammaging and Muscle Protein Metabolism

July 18, 2018 updated by: Ioannis G. Fatouros, University of Thessaly

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Tríkala, Greece, 42100
        • Exercise Biochemistry Laboratory, School of Physical Education & Sports Sciences, University of Thessaly

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

63 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: High systemic inflammation
Individuals assigned in the high systemic inflammation group will be characterized by IL6: ≥ 1.7 pg/ml and hs-CRP: > 2.0 mg/L.
Dietary supplement: Instantized Whey Protein Isolate
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.
ACTIVE_COMPARATOR: Low systemic inflammation
Individuals assigned in the high systemic inflammation group will be characterized by IL6: < 1.7 pg/ml and hs-CRP: < 1.0 mg/L.
Dietary supplement: Instantized Whey Protein Isolate
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At baseline.
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.
At baseline and 180 min following protein ingestion.
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.
At baseline and 180 min following protein ingestion.
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.
At baseline and 180 min following protein ingestion.
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.
At baseline and 180 min following protein ingestion.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Resting metabolic rate (RMR)
Time Frame: At baseline.
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.
At baseline.
Physical activity
Time Frame: Over a 7-day period at baseline.
Level of habitual physical activity will be assessed using accelerometry (ActiGraph GT3X-BT accelerometer).
Over a 7-day period at baseline.
Dietary intake
Time Frame: Over a 7-day period at baseline.
Daily dietary intake will be assessed using 7-day diet recalls.
Over a 7-day period at baseline.
Reduced glutathione in blood
Time Frame: At baseline.
Concentration of reduced glutathione will be measured in red blood cells
At baseline.
Oxidized glutathione in blood
Time Frame: At baseline.
Concentration of oxidized glutathione will be measured in red blood cells
At baseline.
Protein carbonyls in serum
Time Frame: At baseline.
Concentration of protein carbonyls will be measured in serum.
At baseline.
Total antioxidant capacity
Time Frame: At baseline.
Total antioxidant capacity will be measured in serum
At baseline.
Malondialdehyde in serum
Time Frame: At baseline.
Concentration of malondialdehyde will be measured in serum.
At baseline.
White blood cell count in blood
Time Frame: At baseline.
White blood cell count will be measured in blood.
At baseline.
Insulin sensitivity
Time Frame: At baseline.
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.
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.
Glucose concentration will be measured in plasma during the clinical trial.
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.
Insulin concentration will be measured in plasma during the clinical trial.
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 composition will be measured using a dual-energy x-ray absorptiometry scanner (DEXA).
At baseline
Body Mass Index (BMI)
Time Frame: At baseline
Calculated as body mass (kg) divided by the height (m) squared.
At baseline
Skeletal muscle index
Time Frame: At baseline
Calculated as an appendicular lean mass (kg) divided by height (m) squared.
At baseline
Grip strength
Time Frame: At baseline
Using handgrip dynamometry (left and right arm) in a sitting position.
At baseline
Functional performance
Time Frame: At baseline
Functional performance will be assessed using the Short Physical Performance Battery (SPPB).
At baseline
Lower limb muscle strength
Time Frame: At baseline
Will be assessed by defining the 1 repetition maximum (1RM) on a knee-extension machine.
At baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Thessaly

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: DIMITRIOS DRAGANIDIS, PhDc, UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 15, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 2, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 13, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 19, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INFLAMMAGING-UTH

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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