End-stage Renal DiseaseSummerMRINCT04067752
Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease
A study testing high dialysate sodium concentration (138 mEq/L) and Low dialysate sodium concentration in people with End-stage Renal Disease, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
By 2030 an estimated 2 million people in the US will need dialysis or transplantation. Insulin resistance and chronic inflammation are common in dialysis patients and have been linked to protein-energy wasting, the most important determinant of clinical outcome in this patient population. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- End-stage Renal Disease
- What is being tested?
- high dialysate sodium concentration (138 mEq/L) and Low dialysate sodium concentration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Mar 2022to 20 May 2024
- 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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- On MHD for more than 6 months
- Have acceptable dialysis adequacy (eKt/V > 1.2) for a minimum of 3 months and a patent, well-functioning, hemodialysis AV access
- Ability to give informed consent
Who cannot join
- Pregnancy
- Intolerance to the medication in metabolic studies)
- Presence of a metal object in the body that might interfere with MRI
- Severe, unstable, active, or chronic inflammatory disease (active infection, active connective tissue disorder, active cancer or cancer history in the prior 5 years, HIV, liver disease, active chronic hepatitis B or C)
- Type 1 Diabetes on insulin therapy; Hospitalization within 1 month prior to the study
- Receiving steroids (including inhaled steroid and high potency topical, with the exception of over the counter hydrocortisone cream
- Prednisone > 5 mg/day) and/or other immunosuppressive agents
- Residual renal function > 5ml/min or urine output > 400 ml/day
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
Nashville, Tennessee, 37212-2637
Vanderbilt University Medical center
Nashville, Tennessee, 37232
About this study
By 2030 an estimated 2 million people in the US will need dialysis or transplantation. Insulin resistance and chronic inflammation are common in dialysis patients and have been linked to protein-energy wasting, the most important determinant of clinical outcome in this patient population. The investigators hypothesize that the skin and muscle tissue sodium accumulation is a critical mechanism by which chronic inflammatory response and insulin resistance, alone or in combination lead to protein energy wasting in hemodialysis patients. The investigators will test this hypothesis by studying dialysis patients and matched controls without kidney disease by examining tissue Na content, markers of inflammation and protein metabolism.
Read the detailed description
There are more than 420,000 patients receiving maintenance hemodialysis therapy in the United States, which is estimated to rise to over 500,000 patients by 2020. There are an estimated 45,500 Veterans receiving hemodialysis, of which over 3,000 enrolled Veterans were receiving dialysis at VA facilities in FY 2013. Over the last decade, there have been no therapies proven to significantly lower the mortality and morbidity risk for these patients. One of the most important determinants of this poor clinical outcome is protein energy wasting, a highly prevalent nutritional and metabolic abnormality characterized by increased protein breakdown in the skeletal muscle compartment. The investigators' group has shown that two well-recognized and interrelated metabolic abnormalities, insulin resistance and persistent inflammation, are likely to play a critical role in the pathogenesis of protein energy wasting and related nutritional and metabolic abnormalities. The investigators' preliminary data show that in maintenance hemodialysis (MHD) patients 1) There is an inadequate response to protein anabolic actions of insulin; 2) Persistent systemic inflammation is strongly and independently associated with skeletal muscle net protein balance; and 3) Pharmacological modulation of systemic inflammation and insulin resistance partially, but not fully, reverse net protein catabolism. It was demonstrated that non-osmotic sodium (Na) is stored in skin and muscle without commensurate water retention, which leads to local immune-cell activation and accelerated pro-inflammatory status. The investigators' preliminary data show that the skin and muscle Na+ contents, derived by 23Na magnetic resonance imaging (MRI) are substantially higher in MHD patients compared to matched healthy controls. The investigators also showed that increased skin and muscle Na concentrations are significantly associated with increased inflammatory response and decreased peripheral insulin sensitivity, in patients on MHD. These data suggest that tissue Na content, immune pathways and insulin resistance are closely linked and could lead to increased risk for protein energy wasting in MHD patients. It was reported that standard 4-hour conventional hemodialysis provides significant Na removal from muscle and skin suggesting that tissue Na and water content could be modulated by modulating hemodialysis prescription. The overall goal of this application is to elucidate the mechanisms by which tissue sodium accumulation, persistent immune system activation and insulin resistance influence the development of protein energy wasting in MHD patients. The investigators hypothesize that the skin and muscle tissue sodium accumulation is a critical mechanism by which chronic inflammatory response and insulin resistance, alone or in combination, lead to protein energy wasting in MHD patients. Specific Aims: To test the hypothesis that removal of tissue sodium by modulating hemodialysis prescription would improve metabolic milieu and protein energy wasting in MHD patients. The investigators will achieve this goal through a cross-over randomized clinical trial whereby dialysate sodium concentrations will be modulated (138 mEq/L versus 132 mEq/L, 4 weeks each) to remove 10% of baseline skeletal muscle Na content in the setting of stable sodium intake by diet. The primary outcomes will be markers of net protein balance, inflammation, and macronutrient disposal rates. If successful, the proposed studies will have great potential to influence clinical practices in MHD patients because the proposed intervention protocol would be easily accessible and could ultimately lead to improvements in the hospitalization and death rates with great impact on Veterans' Health Care and make important contributions to the research mission of the Department of Veterans Administration.
- Conditions
- End-stage Renal Disease
- Being tested
- high dialysate sodium concentration (138 mEq/L), Low dialysate sodium concentration
- Keywords
- dialysis, ESRD, hemodialysis, MRI
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high dialysate sodium concentration (138 mEq/L)Other
high dialysate sodium concentration (138 mEq/L)
Low dialysate sodium concentrationOther
low dialysate sodium concentration (132 mEq/L)
| Study group | Role | What they receive |
|---|---|---|
| High Dialysate Na | Experimental | high dialysate sodium concentration (138 mEq/L) Receives: Other: high dialysate sodium concentration (138 mEq/L) |
| Low Dialysate Na | Active comparator | Low dialysate sodium concentration (132 mEq/L) Receives: Other: Low dialysate sodium concentration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min
Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min. This reflects the balance between endogenous leucine appearance rate (protein synthesis), the leucine oxidation rate, and the non-oxidative leucine disappearance rate (protein breakdown).
Measured: 4 weeks
Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min
Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min. This reflects the dilution and enrichment of phenylalanine across the forearm. Because phenylalanine is neither synthesized nor metabolized by skeletal muscle, rate of appearance (Ra) of unlabeled phenylalanine reflects muscle protein breakdown, whereas the rate of disappearance (Rd) of labeled phenylalanine estimates muscle protein synthesis. the difference between synthesis and breakdown provides net skeletal muscle protein balance at a given rate of blood flow.
Measured: 4 weeks
Muscle sodium content
Muscle sodoium content measured by NAMRI before and after intervention
Measured: 4 weeks
Skin sodium content
Skin sodium content measured by NAMRI before and after intervention
Measured: 4 weeks
Secondary outcomes (9)
Handgrip strength measured by dynamometer
Handgrip strength (HGS) will be measured on the non stula side before dialysis session using a Jamar hydraulic dynamometer.
Measured: 4 weeks
Recovery time
Patients will be asked how long it took them to recover completely from the preceding session
Measured: 4 weeks
Pulse Wave Velocity
Pulse Wave Velocity will be measured by Sphygmocor.
Measured: 4 weeks
Interleukin 6
proinflammatory cytokine IL6 will be measured as a inflammatory marker
Measured: 4 weeks
Sit to stand test
measurement of how many sit to stands can be accomplished at a given time period to assess physical function
Measured: 4 weeks
Short Physical Performance Battery
Balance, gait speed and chair speed tests will be scored to provide a complete score to assess physical function
Measured: 4 weeks
6-minute walk
measurement of how long can a patient walk within 6 minutes to assess physical function
Measured: 4 weeks
hsCRP
hsCRP will be measured as a marker of systemic inflammation
Measured: 4 weeks
Interleukin 1
Proinflammatory cytokine Interleukin 1 (IL1) will be measured as a inflammatory marker
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start1 Mar 2022
- Primary completion15 May 2024
- Study completion20 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The design is randomized, cross-over, double-blind, placebo-controlled. Once the subject is determined to be eligible for the study, we will randomly assign him/her to one of the study arms (Dialysate Na concentration 138 mEq/L versus 132 mEq/L)
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Talat A Ikizler, MD, Principal investigator, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04067752
- Sponsor's protocol ID
- NEPH-010-18F
- Acronym
- SummerMRI
- Status last verified
- Nov 2024
- First submitted
- 19 Aug 2019
- Last updated
- 8 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ertuglu LA, Sahinoz M, Alsouqi A, Deger SM, Guide A, Pike M, Robinson-Cohen C, Akwo E, Pridmore M, Crescenzi R, Madhur MS, Kirabo A, Harrison DG, Luft FC, Titze J, Ikizler TA, Gamboa JL. Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals. Physiol Rep. 2024 Jul;12(13):e16127. doi: 10.14814/phy2.16127.
PubMed 38960895
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease
- ClinicalTrials.gov ID
- NCT04067752
- Acronym / sponsor ID
- SummerMRI / NEPH-010-18F
- Conditions
- End-stage Renal Disease
- Keywords
- dialysis, ESRD, hemodialysis, MRI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 15 May 2024 (actual)
- Study completion
- 20 May 2024 (actual)
- First posted
- 26 Aug 2019 (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.
By 2030 an estimated 2 million people in the US will need dialysis or transplantation. Insulin resistance and chronic inflammation are common in dialysis patients and have been linked to protein-energy wasting, the most important determinant of clinical outcome in this patient population. The investigators hypothesize that the skin and muscle tissue sodium accumulation is a critical mechanism by which chronic inflammatory response and insulin resistance, alone or in combination lead to protein energy wasting in hemodialysis patients. The investigators will test this hypothesis by studying dialysis patients and matched controls without kidney disease by examining tissue Na content, markers of inflammation and protein metabolism.
Detailed description
There are more than 420,000 patients receiving maintenance hemodialysis therapy in the United States, which is estimated to rise to over 500,000 patients by 2020. There are an estimated 45,500 Veterans receiving hemodialysis, of which over 3,000 enrolled Veterans were receiving dialysis at VA facilities in FY 2013. Over the last decade, there have been no therapies proven to significantly lower the mortality and morbidity risk for these patients. One of the most important determinants of this poor clinical outcome is protein energy wasting, a highly prevalent nutritional and metabolic abnormality characterized by increased protein breakdown in the skeletal muscle compartment. The investigators' group has shown that two well-recognized and interrelated metabolic abnormalities, insulin resistance and persistent inflammation, are likely to play a critical role in the pathogenesis of protein energy wasting and related nutritional and metabolic abnormalities. The investigators' preliminary data show that in maintenance hemodialysis (MHD) patients 1) There is an inadequate response to protein anabolic actions of insulin; 2) Persistent systemic inflammation is strongly and independently associated with skeletal muscle net protein balance; and 3) Pharmacological modulation of systemic inflammation and insulin resistance partially, but not fully, reverse net protein catabolism. It was demonstrated that non-osmotic sodium (Na) is stored in skin and muscle without commensurate water retention, which leads to local immune-cell activation and accelerated pro-inflammatory status. The investigators' preliminary data show that the skin and muscle Na+ contents, derived by 23Na magnetic resonance imaging (MRI) are substantially higher in MHD patients compared to matched healthy controls. The investigators also showed that increased skin and muscle Na concentrations are significantly associated with increased inflammatory response and decreased peripheral insulin sensitivity, in patients on MHD. These data suggest that tissue Na content, immune pathways and insulin resistance are closely linked and could lead to increased risk for protein energy wasting in MHD patients. It was reported that standard 4-hour conventional hemodialysis provides significant Na removal from muscle and skin suggesting that tissue Na and water content could be modulated by modulating hemodialysis prescription. The overall goal of this application is to elucidate the mechanisms by which tissue sodium accumulation, persistent immune system activation and insulin resistance influence the development of protein energy wasting in MHD patients. The investigators hypothesize that the skin and muscle tissue sodium accumulation is a critical mechanism by which chronic inflammatory response and insulin resistance, alone or in combination, lead to protein energy wasting in MHD patients. Specific Aims: To test the hypothesis that removal of tissue sodium by modulating hemodialysis prescription would improve metabolic milieu and protein energy wasting in MHD patients. The investigators will achieve this goal through a cross-over randomized clinical trial whereby dialysate sodium concentrations will be modulated (138 mEq/L versus 132 mEq/L, 4 weeks each) to remove 10% of baseline skeletal muscle Na content in the setting of stable sodium intake by diet. The primary outcomes will be markers of net protein balance, inflammation, and macronutrient disposal rates. If successful, the proposed studies will have great potential to influence clinical practices in MHD patients because the proposed intervention protocol would be easily accessible and could ultimately lead to improvements in the hospitalization and death rates with great impact on Veterans' Health Care and make important contributions to the research mission of the Department of Veterans Administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The design is randomized, cross-over, double-blind, placebo-controlled. Once the subject is determined to be eligible for the study, we will randomly assign him/her to one of the study arms (Dialysate Na concentration 138 mEq/L versus 132 mEq/L)
| Arm | Type | Receives |
|---|---|---|
| High Dialysate Na | Experimental | Other: high dialysate sodium concentration (138 mEq/L)high dialysate sodium concentration (138 mEq/L) |
| Low Dialysate Na | Active comparator | Other: Low dialysate sodium concentrationLow dialysate sodium concentration (132 mEq/L) |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- On MHD for more than 6 months
- Have acceptable dialysis adequacy (eKt/V > 1.2) for a minimum of 3 months and a patent, well-functioning, hemodialysis AV access
- Ability to give informed consent
Key exclusion criteria (8 listed)
- Pregnancy
- Intolerance to the medication in metabolic studies)
- Presence of a metal object in the body that might interfere with MRI
- Severe, unstable, active, or chronic inflammatory disease (active infection, active connective tissue disorder, active cancer or cancer history in the prior 5 years, HIV, liver disease, active chronic hepatitis B or C)
- Type 1 Diabetes on insulin therapy; Hospitalization within 1 month prior to the study
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 |
|---|---|---|
| high dialysate sodium concentration (138 mEq/L)high dialysate sodium concentration (138 mEq/L) | Other | High Dialysate Na |
| Low dialysate sodium concentrationlow dialysate sodium concentration (132 mEq/L) | Other | Low Dialysate Na |
Primary outcome
Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min
Time frame: 4 weeks
Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min. This reflects the balance between endogenous leucine appearance rate (protein synthesis), the leucine oxidation rate, and the non-oxidative leucine disappearance rate (protein breakdown).
Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min
Time frame: 4 weeks
Net skeletal muscle protein balance measured by stable isotope technique reported as g/100 ml/min. This reflects the dilution and enrichment of phenylalanine across the forearm. Because phenylalanine is neither synthesized nor metabolized by skeletal muscle, rate of appearance (Ra) of unlabeled phenylalanine reflects muscle protein breakdown, whereas the rate of disappearance (Rd) of labeled phenylalanine estimates muscle protein synthesis. the difference between synthesis and breakdown provides net skeletal muscle protein balance at a given rate of blood flow.
Muscle sodium content
Time frame: 4 weeks
Muscle sodoium content measured by NAMRI before and after intervention
Skin sodium content
Time frame: 4 weeks
Skin sodium content measured by NAMRI before and after intervention
9 secondary outcomes
Handgrip strength measured by dynamometer
Time frame: 4 weeks
Recovery time
Time frame: 4 weeks
Pulse Wave Velocity
Time frame: 4 weeks
Interleukin 6
Time frame: 4 weeks
Sit to stand test
Time frame: 4 weeks
Short Physical Performance Battery
Time frame: 4 weeks
6-minute walk
Time frame: 4 weeks
hsCRP
Time frame: 4 weeks
Interleukin 1
Time frame: 4 weeks
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 8 Nov 2024.
- Background: PubMed 38960895Ertuglu LA, Sahinoz M, Alsouqi A, Deger SM, Guide A, Pike M, Robinson-Cohen C, Akwo E, Pridmore M, Crescenzi R, Madhur MS, Kirabo A, Harrison DG, Luft FC, Titze J, Ikizler TA, Gamboa JL. Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals. Physiol Rep. 2024 Jul;12(13):e16127. doi: 10.14814/phy2.16127.
- Individual participant dataSharing planned: No
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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.
Talat A Ikizler, MD principal investigator
Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing high dialysate sodium concentration (138 mEq/L) and Low dialysate sodium concentration in people with End-stage Renal Disease, run by VA Office of Research and Development at 2 sites 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 3 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 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Net whole-body muscle protein balance measured by stable isotope technique reported as mg/kg.fat free mass/min (time frame: 4 weeks). The study lists 4 primary outcomes in all. 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 NCT04067752, which also lists 1 linked publication.
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 8 Nov 2024.