Muscle LossNCT03478722
Muscle Protein Synthesis in Dialysis Patients
An observational study of Muscle Loss, run by University of Illinois at Urbana-Champaign at 1 site in United States.
Trial summary
The most severe form of chronic renal failure is end-stage-renal-disease with maintenance hemodialysis (MHD) as the most common treatment strategy. MHD patients experience a number of metabolic and phenotypic derangements including skeletal muscle wasting. Read more about this study
- Who is it for?
- Ages 20 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Muscle Loss
- What is being tested?
- Protein Meal and Stable Isotope Amino Acid Infusion
- Type of treatment
- Injection or infusion
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2017to 1 Apr 2018
- Phase
- Observational
- 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 20 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: In total, the investigators would like to recruit 8 maintenance hemodialysis patients (both male and female) and 8 healthy controls matched for gender, age and BMI.
Who may be able to join
- Aged 20-80 years (both healthy controls and MHD patients)
- Medical clearance from a Nephrologist at their respective dialysis clinic to participate (MHD patients)
Who cannot join
- Known allergies to egg consumption (both healthy controls and MHD patients)
- Phenylketonuria (both healthy controls and MHD patients)
- Vegans (both healthy controls and MHD patients)
- Diagnosed GI tract diseases (healthy controls)
- Recent (1 year) participation in amino acid tracer studies (both healthy controls and MHD patients)
- Predisposition to hypertrophic scarring or keloid formation (both healthy controls and MHD patients)
- Diabetes (healthy controls)
- Pregnancy (both healthy controls and MHD patients)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Protein Ingestion on Postprandial Protein Handling in Hemodialysis Patients
The most severe form of chronic renal failure is end-stage-renal-disease with maintenance hemodialysis (MHD) as the most common treatment strategy. MHD patients experience a number of metabolic and phenotypic derangements including skeletal muscle wasting. Previously, it has been demonstrated that dialysis treatment leads to increased rates of forearm phenylalanine uptake (proxy for 'muscle' protein synthesis) with an even greater rates of phenylalanine release (proxy for 'muscle' protein breakdown). Hence, the dialysis procedure itself is catabolic and induces a catabolic carryover for several hours after dialysis. This suggests prolonged post-dialysis disturbances in whole body- and skeletal muscle protein metabolism in MHD patients. Moreover, dialysis treatment in itself results in ~20 % losses of circulating amino acids in the dialysate. Collectively, this creates the need for replacement of amino acids by protein supplementation during and/or after dialysis. The ingestion of protein-dense meals in between dialysis treatments likely represents an important dietary strategy to counterbalance dialysis-induced catabolism and to achieve the current recommended protein intakes (set at 1.2 g/kg bodyweight/d) to limit muscle protein loss in MHD patients. However, the effectiveness of protein-rich meal ingestion to augment postprandial whole body and muscle protein metabolic responses in MHD patients outside of the dialysis period remain largely undefined.
The purpose of this study is to compare basal and postprandial whole body leucine body kinetics, muscle anabolic sensing mechanisms, markers of muscle proteolysis, and myofibillar protein synthesis rates to mixed meal ingestion on a non-dialysis day in eight MHD patients, between 20-80 and to compare these outcomes to age- and BMI-matched controls. The investigators will use specifically produced intrinsically L-[5,5,5-2H3]leucine labeled eggs combined with primed constant amino acid tracer infusion methods and concomitant blood and muscle direct sampling to make direct assessments of in vivo protein digestion and absorption kinetics and subsequent postprandial muscle protein synthetic responses in MHD patents and controls. On the test day, subjects will remain sedentary for the determination of muscle protein synthesis in both the fasted state and after consumption of the meal.
Read the detailed description
On the day of the infusion trial, participants will report to the laboratory at 0700 h after an overnight fast. MHD patients will be studied ~24 h after their dialysis treatment. A Teflon catheter will be inserted into an antecubital vein for baseline blood sample collection (t=-180 min) after which participants receive priming doses of NaH13CO2 (2.35 µmol·kg), L-[1-13C]leucine (7.6 µmol·kg FFM), and L-[ring-2H5]phenylalanine (2.0 µmol·kg FFM). Subsequently, a continuous intravenous infusion of L-[1-13C]leucine (0.10 µmol·kg FFM ·min) and L-[ring-2H5]phenylalanine (0.05 µmol·kg-1 FFM·min) will be initiated (t=-180 min) and maintained until the end of the trial. A second Teflon catheter will be inserted into a heated dorsal hand vein of the same arm for repeated arterialized blood sampling and will remain patent by a 0.9% saline drip. In the postabsorptive state, muscle biopsies will be collected at t=-120 and -0 min of the infusion. Subsequently, participants will consume a mixed meal containing 20 grams of dietary protein and the completion of the meal will mark the start of the postprandial phase (t=0 min). An additional muscle biopsy will be collected at 300 min to determine postprandial myofibrillar protein synthesis rates. Biopsies will be collected from the middle region of the vastus lateralis (15 cm above the patella) with a Bergström needle modified for suction under local anesthesia (2% Lidocaine). The postabsorptive muscle biopsies will be collected from the same incision with the needle pointed to distal and proximal directions, respectively. The postprandial biopsy will be collected through a separate incision 2-3 cm above the postabsorptive incision. All biopsy samples will be freed from any visible blood, adipose, and connective tissue immediately frozen in liquid nitrogen, and stored at -80˚C until subsequent analysis.
- Conditions
- Muscle Loss
- Being tested
- Protein Meal, Stable Isotope Amino Acid Infusion
- Medical subject headings
- Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein MealOther
Ingestion of mixed meal containing 20 g of dietary protein
Stable Isotope Amino Acid InfusionOther
Continuous infusion of L-[1-13C]leucine (0.13 μmol⋅kg⋅min) and L-[ring- 2H5]phenylalanine (0.05 μmol⋅kg⋅min)
| Study group | Role | What they receive |
|---|---|---|
| Maintenance Hemodialysis Patients | Protein meal, stable isotope amino acid infusion Receives: Other: Protein Meal; Other: Stable Isotope Amino Acid Infusion | |
| Control Subjects | Protein meal, stable isotope amino acid infusion Receives: Other: Protein Meal; Other: Stable Isotope Amino Acid Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional synthetic rate of myofibrillar proteins
Measurement of muscle protein synthesis
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start18 Jan 2017
- Primary completion15 Dec 2017
- Study completion1 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle LossStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Urbana-Champaign
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicholas A Burd, PhD, Principal investigator, University of Illinois, Urbana-Champaign
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03478722
- Sponsor's protocol ID
- 16203
- Status last verified
- Mar 2018
- First submitted
- 19 Mar 2018
- Last updated
- 1 May 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 1 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Protein Ingestion on Postprandial Protein Handling in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT03478722
- Acronym / sponsor ID
- 16203
- Conditions
- Muscle Loss
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of Illinois at Urbana-ChampaignUniversity, hospital or other
- Study start
- 18 Jan 2017 (actual)
- Primary completion
- 15 Dec 2017 (actual)
- Study completion
- 1 Apr 2018 (actual)
- First posted
- 27 Mar 2018 (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 most severe form of chronic renal failure is end-stage-renal-disease with maintenance hemodialysis (MHD) as the most common treatment strategy. MHD patients experience a number of metabolic and phenotypic derangements including skeletal muscle wasting. Previously, it has been demonstrated that dialysis treatment leads to increased rates of forearm phenylalanine uptake (proxy for 'muscle' protein synthesis) with an even greater rates of phenylalanine release (proxy for 'muscle' protein breakdown). Hence, the dialysis procedure itself is catabolic and induces a catabolic carryover for several hours after dialysis. This suggests prolonged post-dialysis disturbances in whole body- and skeletal muscle protein metabolism in MHD patients. Moreover, dialysis treatment in itself results in ~20 % losses of circulating amino acids in the dialysate. Collectively, this creates the need for replacement of amino acids by protein supplementation during and/or after dialysis. The ingestion of protein-dense meals in between dialysis treatments likely represents an important dietary strategy to counterbalance dialysis-induced catabolism and to achieve the current recommended protein intakes (set at 1.2 g/kg bodyweight/d) to limit muscle protein loss in MHD patients. However, the effectiveness of protein-rich meal ingestion to augment postprandial whole body and muscle protein metabolic responses in MHD patients outside of the dialysis period remain largely undefined.
The purpose of this study is to compare basal and postprandial whole body leucine body kinetics, muscle anabolic sensing mechanisms, markers of muscle proteolysis, and myofibillar protein synthesis rates to mixed meal ingestion on a non-dialysis day in eight MHD patients, between 20-80 and to compare these outcomes to age- and BMI-matched controls. The investigators will use specifically produced intrinsically L-[5,5,5-2H3]leucine labeled eggs combined with primed constant amino acid tracer infusion methods and concomitant blood and muscle direct sampling to make direct assessments of in vivo protein digestion and absorption kinetics and subsequent postprandial muscle protein synthetic responses in MHD patents and controls. On the test day, subjects will remain sedentary for the determination of muscle protein synthesis in both the fasted state and after consumption of the meal.
Detailed description
On the day of the infusion trial, participants will report to the laboratory at 0700 h after an overnight fast. MHD patients will be studied ~24 h after their dialysis treatment. A Teflon catheter will be inserted into an antecubital vein for baseline blood sample collection (t=-180 min) after which participants receive priming doses of NaH13CO2 (2.35 µmol·kg), L-[1-13C]leucine (7.6 µmol·kg FFM), and L-[ring-2H5]phenylalanine (2.0 µmol·kg FFM). Subsequently, a continuous intravenous infusion of L-[1-13C]leucine (0.10 µmol·kg FFM ·min) and L-[ring-2H5]phenylalanine (0.05 µmol·kg-1 FFM·min) will be initiated (t=-180 min) and maintained until the end of the trial. A second Teflon catheter will be inserted into a heated dorsal hand vein of the same arm for repeated arterialized blood sampling and will remain patent by a 0.9% saline drip. In the postabsorptive state, muscle biopsies will be collected at t=-120 and -0 min of the infusion. Subsequently, participants will consume a mixed meal containing 20 grams of dietary protein and the completion of the meal will mark the start of the postprandial phase (t=0 min). An additional muscle biopsy will be collected at 300 min to determine postprandial myofibrillar protein synthesis rates. Biopsies will be collected from the middle region of the vastus lateralis (15 cm above the patella) with a Bergström needle modified for suction under local anesthesia (2% Lidocaine). The postabsorptive muscle biopsies will be collected from the same incision with the needle pointed to distal and proximal directions, respectively. The postprandial biopsy will be collected through a separate incision 2-3 cm above the postabsorptive incision. All biopsy samples will be freed from any visible blood, adipose, and connective tissue immediately frozen in liquid nitrogen, and stored at -80˚C until subsequent analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maintenance Hemodialysis Patients | – | Other: Protein Meal, Other: Stable Isotope Amino Acid InfusionProtein meal, stable isotope amino acid infusion |
| Control Subjects | – | Other: Protein Meal, Other: Stable Isotope Amino Acid InfusionProtein meal, stable isotope amino acid infusion |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- In total, the investigators would like to recruit 8 maintenance hemodialysis patients (both male and female) and 8 healthy controls matched for gender, age and BMI.
Key inclusion criteria (2 listed)
- Aged 20-80 years (both healthy controls and MHD patients)
- Medical clearance from a Nephrologist at their respective dialysis clinic to participate (MHD patients)
Key exclusion criteria (8 listed)
- Known allergies to egg consumption (both healthy controls and MHD patients)
- Phenylketonuria (both healthy controls and MHD patients)
- Vegans (both healthy controls and MHD patients)
- Diagnosed GI tract diseases (healthy controls)
- Recent (1 year) participation in amino acid tracer studies (both healthy controls and MHD patients)
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 |
|---|---|---|
| Protein MealIngestion of mixed meal containing 20 g of dietary protein | Other | Control Subjects, Maintenance Hemodialysis Patients |
| Stable Isotope Amino Acid InfusionContinuous infusion of L-[1-13C]leucine (0.13 μmol⋅kg⋅min) and L-[ring- 2H5]phenylalanine (0.05 μmol⋅kg⋅min) | Other | Control Subjects, Maintenance Hemodialysis Patients |
Primary outcome
Fractional synthetic rate of myofibrillar proteins
Time frame: 8 hours
Measurement of muscle protein synthesis
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 1 May 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.
Nicholas A Burd, PhD principal investigator
University of Illinois, Urbana-Champaign
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Muscle Loss, run by University of Illinois at Urbana-Champaign at 1 site in United States.
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 8 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 1 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 States. 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?
Fractional synthetic rate of myofibrillar proteins (time frame: 8 hours). 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 1 May 2018.