Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inflammaging and Muscle Protein Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03308747
Recruitment Status : Completed
First Posted : October 13, 2017
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Ioannis G. Fatouros, University of Thessaly

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Inflammaging Sarcopenia Dietary Supplement: Instantized Whey Protein Isolate Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Low-grade Systemic Inflammation on Muscle Protein Synthesis and Breakdown in the Aged Skeletal Muscle.
Actual Study Start Date : September 1, 2017
Actual Primary Completion Date : February 15, 2018
Actual Study Completion Date : May 30, 2018

Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. Dietary intake [ Time Frame: Over a 7-day period at baseline. ]
    Daily dietary intake will be assessed using 7-day diet recalls.

  4. Reduced glutathione in blood [ Time Frame: At baseline. ]
    Concentration of reduced glutathione will be measured in red blood cells

  5. Oxidized glutathione in blood [ Time Frame: At baseline. ]
    Concentration of oxidized glutathione will be measured in red blood cells

  6. Protein carbonyls in serum [ Time Frame: At baseline. ]
    Concentration of protein carbonyls will be measured in serum.

  7. Total antioxidant capacity [ Time Frame: At baseline. ]
    Total antioxidant capacity will be measured in serum

  8. Malondialdehyde in serum [ Time Frame: At baseline. ]
    Concentration of malondialdehyde will be measured in serum.

  9. White blood cell count in blood [ Time Frame: At baseline. ]
    White blood cell count will be measured in blood.

  10. 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.

  11. 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.

  12. 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.

  13. Body composition [ Time Frame: At baseline ]
    Body composition will be measured using a dual-energy x-ray absorptiometry scanner (DEXA).

  14. Body Mass Index (BMI) [ Time Frame: At baseline ]
    Calculated as body mass (kg) divided by the height (m) squared.

  15. Skeletal muscle index [ Time Frame: At baseline ]
    Calculated as an appendicular lean mass (kg) divided by height (m) squared.

  16. Grip strength [ Time Frame: At baseline ]
    Using handgrip dynamometry (left and right arm) in a sitting position.

  17. Functional performance [ Time Frame: At baseline ]
    Functional performance will be assessed using the Short Physical Performance Battery (SPPB).

  18. Lower limb muscle strength [ Time Frame: At baseline ]
    Will be assessed by defining the 1 repetition maximum (1RM) on a knee-extension machine.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   63 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03308747


Locations
Layout table for location information
Greece
Exercise Biochemistry Laboratory, School of Physical Education & Sports Sciences, University of Thessaly
Tríkala, Greece, 42100
Sponsors and Collaborators
University of Thessaly
Investigators
Layout table for investigator information
Principal Investigator: DIMITRIOS DRAGANIDIS, PhDc UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES
Layout table for additonal information
Responsible Party: Ioannis G. Fatouros, Associate Professor, University of Thessaly
ClinicalTrials.gov Identifier: NCT03308747    
Other Study ID Numbers: INFLAMMAGING-UTH
First Posted: October 13, 2017    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: October 2017

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ioannis G. Fatouros, University of Thessaly:
Low-grade systemic inflammation
Muscle protein synthesis
Proteasome activation
Anabolic signaling
Aging
Sarcopenia
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms