Plasma Biomarkers of Muscle Metabolism During Exercise to the Assessment of Insulin Resistance in CKD Dialysis Patients

NCT06360302 | Recruiting

• 1 other identifier: RECHMPL22_0505
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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:

• V'O2-adjusted lactate at rest and during exercise
• The combination of exercise energy metabolism intermediates reflecting insulin resistance among Krebs cycle cofactors/substrates, ß-oxidation cofactors/substrates, amino acids

Conditions

Metabolic Syndrome; Dialysis; Complications

Keywords

exercise test; Citric Acid Cycle; metabolomic

Outcome Measures

Primary Outcomes (1)

• Compare V'O2-adjusted plasma lactate profile at rest and during exercise (metabolic stress test), between chronic renal failure patients, patients with metabolic syndrome and healthy subjects.

  Measurements will be taken every 6 minutes, at rest and during exercise on a cycloergometer, corresponding to intensities of 0% (rest) 20%, 30%, 40%, 50 and 60% of the subject's estimated maximum power. The gas exchange measurement (V'O2 and V'CO2 (milliliter per minute mL/min)) will be carried out cycle-by-cycle using a gas analyzer connected to a flow meter. The intensity corresponding to the rate of maximum lipid oxidation will be defined as LIPOXMAX, and will be expressed in Watts (W), and as a % of theoretical VO2max. Carbohydrate (G) and lipid (L) oxidation rates will be calculated as follows: * G (mg/min) = 4.585 VCO2 - 3.2255 VO2 * L (mg/min) = 1.6946 VO2 - 1.7012 VCO2 Blood sampling at various levels on a peripheral venous catheter synchronized with stress test measurements. A comparison will be made on the basis of an analysis of variance by ANOVA one way after verification of the conditions of application or a rank test by analysis via Kruskal-Wallis.

  Baseline (rest), 6, 12, 18, 24, 30 minutes

Secondary Outcomes (5)

• Compare between the 3 groups their metabolic profile (Krebs cycle cofactors/substrates) adjusted to V'O2 at rest and during exercise.

  Baseline (rest), 6, 12, 18, 24, 30 minutes

• Compare between the 3 groups their metabolic profile (ß-oxidation cofactors/substrates) adjusted to V'O2 at rest and during exercise.

  Baseline (rest), 6, 12, 18, 24, 30 minutes

• Compare between the 3 groups their metabolic profile (amino acids) adjusted to V'O2 at rest and during exercise.

  Baseline (rest), 6, 12, 18, 24, 30 minutes

• Compare between the 3 groups their metabolic profile (acyl-carnitine profiles) adjusted to V'O2 at rest and during exercise.

  Baseline (rest), 6, 12, 18, 24, 30 minutes

• Anthropometry Comparison between the 3 groups

  Baseline (rest)

Study Arms (3)

Healthy volunters

ACTIVE COMPARATOR

Voluntary participants with no chronic diseases aged 40 to 75 wishing to take part in the study and benefit from an exercise test.

Diagnostic Test: Exercise test; Diagnostic Test: Blood sample; Diagnostic Test: Impedancemetry

Metabolic syndrome patients

ACTIVE COMPARATOR

Patients aged 40 to 75 with metabolic syndrome undergoing functional assessment in the physiology department.

Diagnostic Test: Exercise test; Diagnostic Test: Blood sample; Diagnostic Test: Impedancemetry

CKD dialysis patients

EXPERIMENTAL

Chronic renal failure patients on dialysis, stable hemodialysis for more than 3 months

Diagnostic Test: Exercise test; Diagnostic Test: Blood sample; Diagnostic Test: Impedancemetry

Interventions

Exercise test DIAGNOSTIC_TEST

"Metabolic" effort test on cycloergometer with gas measurement. Gas exchanges (V'O2 and V'CO2) will be measured cycle-by-cycle using a gas analyzer connected to a flow meter Measurements will be taken every 6 minutes, at rest and during exercise on a cycloergometer, in five 6-minute increments, corresponding to intensities of 0% (rest), 20%, 30%, 40%, 50 and 60% of the subject's estimated maximum power, for a total duration of around 45 minutes.

CKD dialysis patients; Healthy volunters; Metabolic syndrome patients

Blood sample DIAGNOSTIC_TEST

A catheter will be placed in a forearm vein to take blood samples at rest and at the end of the 5-stage stress test. Sampling times synchronized with stress test measurements

CKD dialysis patients; Healthy volunters; Metabolic syndrome patients

Impedancemetry DIAGNOSTIC_TEST

measurement of anthropometric data (weight, height, waist circumference). impedancemetry will enable body composition to be analyzed by placing surface electrodes on the body. The participant will lie on an examination table and must remain at rest for 5 minutes.

CKD dialysis patients; Healthy volunters; Metabolic syndrome patients

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1: Healthy subjects:
• Postmenopausal women aged 40 to 75 or men aged 40 to 75
• No chronic disease or treatment
• BMI \<30 kg/m², or
• Fasting blood glucose \< 1.10 g/dL
• Group 2: metabolic syndrome patients
• Postmenopausal women aged 40 to 75 or men aged 40 to 75
• Metabolic syndrome as defined by the International Diabetes Federation (IDF 2006)5
• BMI \<30 kg/m² and waist circumference \>80 cm for women and \>94 cm for men
• Insulin resistance defined by HOMA-IR\>2.4
• Group 3: CKD dialysis patients
• Non-diabetics
• Postmenopausal women aged 40 to 75 and men aged 40 to 75
• BMI \<30 kg/m².
• Chronic kidney disease patients on dialysis - stable on HD for more than 3 months

You may not qualify if:

• Non-stabilized pathology incompatible with physical exercise
• Ongoing exercise retraining program
• Nutritional supplementation in the 4 weeks preceding the study (antioxidants, vitamins, etc.)
• Treatment influencing mitochondrial function (metformin, statin, etc.)
• Failure to obtain written informed consent after a period of reflection
• Subject not affiliated to a social security scheme, or not benefiting from such a scheme.
• Person protected by law (under guardianship or curatorship)
• Patient deprived of liberty
• Diabetic patient
• Family dyslipidemia
• Participants who have reached the maximum amount of compensation for their participation in research projects
• Person under psychiatric care
• Mentally handicapped, dementia, illiterate, language barrier with inability to understand study purpose and methodology

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (2)

AIDER Santé Fondation Charles Mion Montpellier, site Lapeyronie

Montpellier, 34295, France

RECRUITING

Montpellier University Hospital

Montpellier, 34295, France

RECRUITING

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Exercise Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative

Study Officials

• GRILLET Pierre-Edouard, Pharma D. PhD

  University Hospital, Montpellier

  STUDY DIRECTOR

Central Study Contacts

GRILLET Pierre-Edouard, Pharma D. PhD

CONTACT

04 67 33 63 81; pe-grillet@chu-montpellier.fr

FARES GOUZI, MD PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cross-sectional comparative study with repeated measures

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 11, 2024
• Study Start: November 18, 2024
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): November 18, 2026
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)