Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06360302
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-11
First Post:
2024-04-08
Brief Title:
Plasma Biomarkers of Muscle Metabolism During Exercise to the Assessment of Insulin Resistance in CKD Dialysis Patients
Sponsor:
University Hospital Montpellier
Organization:
University Hospital Montpellier
Study Overview
Official Title:
Contribution of Plasma Assays of Biomarkers of Muscle Metabolism During Exercise to the Assessment of Insulin Resistance in Chronic Renal Failure Patients Undergoing Hemodialysis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KREBSome-IRC
Brief Summary:
This prospective multicenter cross-sectional repeated-measures comparative study compared functional and biochemical response profiles to exercise between 2 groups of chronically ill patients chronic renal failure dialysis patients and patients with metabolic syndrome and a group of healthy subjects
The hypothesis is that the addition of plasma metabolic intermediates associated with energy disorders linked to insulin resistance will improve the sensitivity of the assessment of muscle oxidative metabolism abnormalities as reported in exercise intolerant subjects
In this way the metabolomics approach during exercise would provide a biological and functional signature of insulin resistance of muscular origin discriminating between insulin-resistant patients healthy control subjects and dialysis patients with an exercise metabolic profile approaching that observed in insulin-resistant patients A better understanding of metabolic abnormalities could guide muscle rehabilitation
Participants will be asked to perform an exercise test with several blood samples taken at different exercise intensities
Researchers will compare the metabolic profile of three groups patients with chronic kidney disease patients with metabolic syndrome and healthy subjects
VO2-adjusted lactate at rest and during exercise
The combination of exercise energy metabolism intermediates reflecting insulin resistance among Krebs cycle cofactorssubstrates ß-oxidation cofactorssubstrates amino acids
The hypothesis is that the addition of plasma metabolic intermediates associated with energy disorders linked to insulin resistance will improve the sensitivity of the assessment of muscle oxidative metabolism abnormalities as reported in exercise intolerant subjects
In this way the metabolomics approach during exercise would provide a biological and functional signature of insulin resistance of muscular origin discriminating between insulin-resistant patients healthy control subjects and dialysis patients with an exercise metabolic profile approaching that observed in insulin-resistant patients A better understanding of metabolic abnormalities could guide muscle rehabilitation
Participants will be asked to perform an exercise test with several blood samples taken at different exercise intensities
Researchers will compare the metabolic profile of three groups patients with chronic kidney disease patients with metabolic syndrome and healthy subjects
VO2-adjusted lactate at rest and during exercise
The combination of exercise energy metabolism intermediates reflecting insulin resistance among Krebs cycle cofactorssubstrates ß-oxidation cofactorssubstrates amino acids
Detailed Description:
Chronic renal failure or CKD is a chronic disease requiring end-stage replacement of renal function by extra-renal purification via hemodialysis HD CKD patients on dialysis suffer from numerous severe co-morbidities limiting the possibility of renal transplantation
Metabolic impairments are numerous and complex dyslipidemia phospho-calcium disorders hormonal and nutritional disturbances
In these patients the onset of insulin resistance is virtually systematic but its assessment remains a challenge In fact the classic screening method known as HOMA-IR using simultaneous measurement of insulin and plasma glucose levels is greatly affected by dialysis and the timing of its implementation The reference method known as the hyperinsulinemic-euglycemic clamp is difficult to perform in HD patients
While insulin resistance is a condition that can be reversed by physical activity in chronic pathologies the absence of a validated assessment method for CKD in HD represents a missed opportunity for prevention in CKD at a time when muscle rehabilitation programs are developing in CKD
Moreover insulin resistance is associated with skeletal striated muscle dysfunction in CKD patients and constitutes another major comorbidity in these patients as skeletal striated muscle is the main tissue utilizing glucose in response to insulin The research team has shown that muscular dysfunctions associating reduced muscle strength andor muscular atrophy are a morbi-mortality factor in dialysis patients Finally molecular abnormalities associate a switch of muscle fibers towards glycolytic fibers and mitochondrial abnormalities strongly suggesting an energy dysfunction
In a preliminary study the research team were able to demonstrate in dialysis patients an alteration in energy metabolism comparable to a loss of metabolic flexibility mimicking that observed in insulin-resistant patients without renal dysfunction A better understanding of the components of energy anomalies and insulin resistance could guide muscle rehabilitation protocols and prevent complications associated with insulin resistance
Currently the only valid non-invasive method used in clinical practice to demonstrate impairment of muscular oxidative metabolism is the measurement of carbohydratelipid utilization rate during an exercise test This metabolic stress test makes it possible to determine the point of maximum lipid utilization LIPOXMAX the current reference marker of muscle metabolism during exercise
Nevertheless LIPOXMAX alone cannot provide an understanding of underlying metabolic abnormalities in energy pathways and the assay of different muscle metabolites released into plasma during exercise and their combination has recently emerged as a specific and early assessment of insulin resistance
In particular parameters such as lactate or pyruvate measured in plasma at rest have been positively correlated with the HOMA-IR index and associated with an increased risk of developing type 2 diabetes During exercise metabolic stress test lactate levels in insulin-resistant patients differ from those in healthy controls
In view of the abnormalities of oxidative muscle metabolism in CKD and insulin-resistant patients the measurement of lactate at rest and during exercise adjusted for VO2 could reveal a profile enabling discrimination of CKD and insulin-resistant patients from healthy control subjects
With the addition of plasma metabolic intermediates associated with energy disorders linked to insulin resistance The investigators hypothesize that their measurement during exercise will improve the sensitivity of the assessment of muscle oxidative metabolism abnormalities as reported in exercise-intolerant subjects
The metabolomics approach during exercise would provide a biological and functional signature of muscle-induced insulin resistance in haemodialysis patients A better understanding of metabolic abnormalities could guide muscle rehabilitation
This prospective cross-sectional repeated-measures comparative study comparing functional and biochemical response profiles to exercise between 2 groups of chronically ill patients and a group of healthy subjects
This comparison of the metabolisms of the 3 groups is analyzed using repeated plasma sampling at different effort intensities
Plasma lactate adjusted to VO2 ratio at rest and during exercise
VO2-adjusted metabolic profile at rest and during exercise through a combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient 07 compared to LIPOXmax andor HOMA-IR among the following
Krebs cycle cofactorssubstrates lactate pyruvate malate citrate succinate fumarate and alpha-cetoglutarate
ß-oxidation cofactorssubstrates free fatty acids acyl-carnitine profile beta-hydroxybutyrate acetoacetate
Amino acid profile
Acyl carnitine profile
Metabolic impairments are numerous and complex dyslipidemia phospho-calcium disorders hormonal and nutritional disturbances
In these patients the onset of insulin resistance is virtually systematic but its assessment remains a challenge In fact the classic screening method known as HOMA-IR using simultaneous measurement of insulin and plasma glucose levels is greatly affected by dialysis and the timing of its implementation The reference method known as the hyperinsulinemic-euglycemic clamp is difficult to perform in HD patients
While insulin resistance is a condition that can be reversed by physical activity in chronic pathologies the absence of a validated assessment method for CKD in HD represents a missed opportunity for prevention in CKD at a time when muscle rehabilitation programs are developing in CKD
Moreover insulin resistance is associated with skeletal striated muscle dysfunction in CKD patients and constitutes another major comorbidity in these patients as skeletal striated muscle is the main tissue utilizing glucose in response to insulin The research team has shown that muscular dysfunctions associating reduced muscle strength andor muscular atrophy are a morbi-mortality factor in dialysis patients Finally molecular abnormalities associate a switch of muscle fibers towards glycolytic fibers and mitochondrial abnormalities strongly suggesting an energy dysfunction
In a preliminary study the research team were able to demonstrate in dialysis patients an alteration in energy metabolism comparable to a loss of metabolic flexibility mimicking that observed in insulin-resistant patients without renal dysfunction A better understanding of the components of energy anomalies and insulin resistance could guide muscle rehabilitation protocols and prevent complications associated with insulin resistance
Currently the only valid non-invasive method used in clinical practice to demonstrate impairment of muscular oxidative metabolism is the measurement of carbohydratelipid utilization rate during an exercise test This metabolic stress test makes it possible to determine the point of maximum lipid utilization LIPOXMAX the current reference marker of muscle metabolism during exercise
Nevertheless LIPOXMAX alone cannot provide an understanding of underlying metabolic abnormalities in energy pathways and the assay of different muscle metabolites released into plasma during exercise and their combination has recently emerged as a specific and early assessment of insulin resistance
In particular parameters such as lactate or pyruvate measured in plasma at rest have been positively correlated with the HOMA-IR index and associated with an increased risk of developing type 2 diabetes During exercise metabolic stress test lactate levels in insulin-resistant patients differ from those in healthy controls
In view of the abnormalities of oxidative muscle metabolism in CKD and insulin-resistant patients the measurement of lactate at rest and during exercise adjusted for VO2 could reveal a profile enabling discrimination of CKD and insulin-resistant patients from healthy control subjects
With the addition of plasma metabolic intermediates associated with energy disorders linked to insulin resistance The investigators hypothesize that their measurement during exercise will improve the sensitivity of the assessment of muscle oxidative metabolism abnormalities as reported in exercise-intolerant subjects
The metabolomics approach during exercise would provide a biological and functional signature of muscle-induced insulin resistance in haemodialysis patients A better understanding of metabolic abnormalities could guide muscle rehabilitation
This prospective cross-sectional repeated-measures comparative study comparing functional and biochemical response profiles to exercise between 2 groups of chronically ill patients and a group of healthy subjects
This comparison of the metabolisms of the 3 groups is analyzed using repeated plasma sampling at different effort intensities
Plasma lactate adjusted to VO2 ratio at rest and during exercise
VO2-adjusted metabolic profile at rest and during exercise through a combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient 07 compared to LIPOXmax andor HOMA-IR among the following
Krebs cycle cofactorssubstrates lactate pyruvate malate citrate succinate fumarate and alpha-cetoglutarate
ß-oxidation cofactorssubstrates free fatty acids acyl-carnitine profile beta-hydroxybutyrate acetoacetate
Amino acid profile
Acyl carnitine profile
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None