Physiopathology of Neuromuscular Function Related to Fatigue in Chronic Renal Disease (PIONEER)

Chronic Kidney Disease (CKD) induces many metabolic troubles especially for the advanced CKD (stage 3b-5) patients and their prevalence and importance grow with the deterioration of the glomerular filtration rate (GFR). Among them, muscle wasting is common and multifactorial, partially explained by an imbalance between protein catabolism and synthesis. Muscular strength is also affected beyond the reduction of the lean body mass, resulting in profound fatigue.

The present study seeks to quantify the prevalence of low muscular strength production (dynapenia) in a cohort of elderly patients with advanced CKD, through a maximal voluntary contraction (MVC) handgrip test compared to control data available in the literature, matched in term of age and sex. It also aims to investigate the link between the reported fatigue (subjective) and the evolution of the MVC, called critical force (fcrit) during a fatiguing task (objective fatigability).

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Chronic Kidney Disease Stage 5; Chronic Kidney Disease stage4; Chronic Kidney Disease Stage 3B
• Intervention / Treatment: Other: Handgrip fatigability test; Other: Questionnaires

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christelle JADEAU; Phone Number: 37482 0033 2 43 43 43 43; Email: cjadeau@ch-lemans.fr
• Study Contact Backup: Name: Giorgina PICCOLI, MD; Phone Number: 37138 0033 2 43 43 43 43; Email: gpiccoli@ch-lemans.fr

Study Locations

• France
  • Le Mans, France, 72000
    • Recruiting
    • Centre Hospitalier du Mans
    • Principal Investigator: Giorgina PICCOLI, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults, aged 60 and over
• Social security coverage
• Signed informed consent
• For patient with Chronic Kidney Disease, estimated glomerular filtration rate (eGFR) less than 45ml/min/1.73m2 (Stage 3b) for at least 3 months
• For patient with Chronic Kidney Disease, stable clinical condition (i.e., Creatinine increased by a maximum of 25% in the previous 3 months)
• For control group, 1:1 recruitment with case matching with CDK patients on gender (i.e., male and female) and the presence of diabètes (i.e., presence and absence)
• For control group, blood test with control of renal function available and dated less than 6 months: with eGFR > 60ml/min/1.73m2 (and control of glucose or glycated hemoglobin for diabetic controls)

Exclusion Criteria:

• Pregnant women
• Under guardianship or minor
• Neuromuscular disease
• Dementia
• Upper limbs history of surgery or pathologies preventing from fitting EMG electrodes or measuring handgrip force
• Life expectancy of less than 3 months estimated by medical judgment
• Programed hospitalization in the previous 3 months
• Participation to another interventional clinical trial
• Acute kidney disease
• On dialysis or expected start of dialysis within next 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patient with chronic kidney disease; Patients will perform a Handgrip fatigability test with their dominant hand and will complete two questionnaires of assessment of subjective fatigue.	Other: Handgrip fatigability test; Dynamometric and electromyographic assessment: patient is sitting on a chair, back upright, humerus vertically placed and forearm landing parallel to a support. Dominant arm is chosen for test and electrodes placement. The assessment is divided in 4 phases for a total of 30 minutes duration: Warm-up, determination of reference force settings (fast sub-maximal contractions and maximal voluntary contractions), fatigability period and rest.; Other: Questionnaires; Assessment of subjective fatigue with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Multidimensional Fatigue Inventory (MFI-20) questionnaires
Other: CONTROL GROUP; Patients will perform a Handgrip fatigability test with their dominant hand and will complete two questionnaires of assessment of subjective fatigue.	Other: Handgrip fatigability test; Dynamometric and electromyographic assessment: patient is sitting on a chair, back upright, humerus vertically placed and forearm landing parallel to a support. Dominant arm is chosen for test and electrodes placement. The assessment is divided in 4 phases for a total of 30 minutes duration: Warm-up, determination of reference force settings (fast sub-maximal contractions and maximal voluntary contractions), fatigability period and rest.; Other: Questionnaires; Assessment of subjective fatigue with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Multidimensional Fatigue Inventory (MFI-20) questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DYNAPENIA	The main outcome of the study is to defined the prevalence of dynapenia for advanced CKD elderly patients. Dynapenia will be established when the mean of the first three MVC of the protocol is lower compared to the reference values appaired for age and sex. For reference values of elderly, please see Ramírez-Vélez et al., (2019).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EMG signal	To analyze the amplitude of the EMG signal recorded, it will be rectified with the Root Mean Square (RMS) method. Frequency analysis will be performed with the Fast Fourier Transform (FFT).	1 day
Objective fatigue	The nmF is an indicator of the objective fatigue, it is identified by measuring the Fcrit during the fatigability period of the protocol (Figure 1). The value of Fcrit is the asymptote of the MVC curve plotted. This value is calculated for each individual.	1 day
Subjective fatigue	The symptom of fatigue will be assessed with two questionnaires, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Multidimensional Fatigue Inventory (MFI-20). FACIT-F is a validated questionnaire in French language (Kwakkenbos et al., 2014), slightly short, including 13 pragmatically and simple affirmations (e.g., I am too tired to eat) with Likert scale (0: "Not at all" to 4: "enormously"). The questionnaire depicted 4 dimensions (i.e., General fatigue, mental fatigue, reduced activities, motivation) and the final score ranges from 0 to 52, with an elevated score depicted a low fatigue. MFI-20 is a validated questionnaire in French language (Gentile et al., 2003) focused about fatigue. It is built with a balance between positive trend questions (e.g., Physically I feel I am in an excellent condition) and negative trend question (e.g., Physically I feel only able to do a little). An elevated score depicted a higher fatigue.	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric data	Only relevant data will be collected from medical folder such as age, sex... to determine anthropometric data.	Within 3 months for the CKD patients, within 6 months for the control volunteers.
Clinical data	Relevant data will be collected from medical folder such as existence of a diabetes, type of kidney disease, time of follow-up, Charlson Comorbidity Index (CCI ; Charlson et al., 1987) and Malnutrition Inflammation Score (Borges et al., 2017) to determine comorbidities data.	Within 3 months for the CKD patients, within 6 months for the control volunteers.
Nutritional data	Relevant data will be collected from medical folder such as Malnutrition Inflammation Score (Borges et al., 2017), Subjective global assessment, albumin, total cholesterol, HDL, LDL, triglycerides, uric acid, blood formula count, creatinine, urea, glycemia, 24 hours proteinuria, pre-albumine, uric acid to determine nutritional status.	Within 3 months for the CKD patients, within 6 months for the control volunteers.
Biochemical data	Relevant data will be collected from medical folder such as calcium, phosphorus, PTH, vitamin D, bicarbonate, sodium and potassium to define biochemical data.	Within 3 months for the CKD patients, within 6 months for the control volunteers.

Collaborators and Investigators

• Sponsor: Centre Hospitalier le Mans
• Collaborators: Le Mans Universite

Publications and helpful links

General Publications

• Chatrenet A, Beaune B, Fois A, Pouliquen C, Audebrand JM, Torreggiani M, Paris D, Durand S, Piccoli GB. PhysIOpathology of NEuromuscular function rElated to fatigue in chronic Renal disease in the elderly (PIONEER): study protocol. BMC Nephrol. 2020 Jul 25;21(1):305. doi: 10.1186/s12882-020-01976-6.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: March 26, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Dynapenia; Neuromuscular abilities; Over-60-year-old patients
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Fatigue; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: CHM-2020/S8/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No