Chronic Kidney Disease (Stages 4 and 5), Mild Cognitive Impairment (MCI)
Conditions
Keywords
Chronic Kidney Disease (CKD), stage G4-5 (CKD G4-5), dialysis, physical exercise, cognitive function
Brief summary
This research project focuses on improving memory and thinking (cognitive function) in people with advanced chronic kidney disease (CKD), a condition that affects about 10% of adults and is often linked to cognitive problems. The study includes a clinical trial where patients will either receive standard care or follow a home-based exercise program involving walking and strength training, to see if regular physical activity can improve brain function. It also includes a large-scale analysis of data from the UK Biobank to explore blood and genetic markers, brain imaging, and lifestyle factors linked to cognitive health. The ultimate aim is to find effective, easy-to-implement strategies and early warning signs that could lead to better treatment and quality of life for people living with CKD.
Detailed description
The project aims to test the impact of exercise programs on cognitive function in stage G 4-5 CKD and dialysis patients with MCI in a randomised clinical trial. A structured physical exercise program (walking exercise) effectively improved physical performance and quality of life in dialysis patients in a previous trial by us (see reference 6 by the investigators of this proposal). We will combine resistance and walking exercise in the active arm of the trial. In parallel with this trial, the project aims to test the cross-sectional and longitudinal relationship between physical activity (PAA) and the genetic and circulatory biomarkers of cognitive function and brain MRI in CKD patients and individuals without CKD in the UK Biobank. Randomised clinical trial This trial will test a structured combined physical exercise program based on home-based aerobic (walking) exercise and resistance exercise maintained for 26 weeks on cognitive function in predialysis patients with advanced CKD (stages 4-5) and dialysis patients with MCI compared to the usual care (control group). In the two study arms, nutritional guidelines by KDIGO will be implemented, and nutrient intake will be periodically assessed. For this purpose, an App for CKD patients, including dietary advice and registering nutrients, will be adapted to the languages of centres in participating countries. Furthermore, body composition will be assessed during the study visits using validated bio-impedance spectroscopy instruments. Two-thirds of enrolees will be predialysis CKD patients and one-third dialysis patients (haemodialysis or peritoneal dialysis patients). Partners or caregivers to assist patients in the trial's exercise arm are requested explicitly for inclusion.
Interventions
BEHAVIORALExercise
Patients will undergo a home-based low-intensity interval multi component exercise program including aerobic and strengthening exercise
OTHERControl (Standard treatment)
Patients will be treated with standard therapy based on their CKD stage
Sponsors
Biogem s.c.ar.l.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CKD at KDOQI stage 4-5 * concomitant MCI (MOCA - MMSE (17 \< MoCA \< 26) or (16 \< MMSE \< 24)
Exclusion criteria
* Absolute contraindication to exercise training (e.g. unstable angina, major amputation, severe heart failure, etc.) * Known life expectancy \< 6-month * Uncorrected anemia (Hb \<9 g/dl) * Non-provision of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive function | Baseline; End of program (6-month); Follow up (12-month; 24-month) | Cognitive function using the Alzheimer Disease Assessment Scale Cognitive 11 (ADAS-Cog-11) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-minute walking test | Baseline; End of program (6-month); Follow up (12-month; 24-month) | The patients will be instructed to walk back and forth on a 20-meter corridor aiming at covering as much distance as possible. The total distance covered (6MWD) will be measured in meters |
| Quality of life assessment | Baseline; end of the program (6-month); Follow up (12-month; 24-month) | Quality of life will be assessed by the short-form 36 (SF-36) questionnaire This is a generic questionnaire that contains 36 questions referring to 8 specific domains related to patient health over the previous 4 weeks |
| Lower limbs strength assessment | Baseline; end of the program (6-month); Follow up (12-month; 24-month) | Lower limbs strength assessed by the 5-time sit-to-stand test Patients will raise up from a standard height chair with their arms folded across the chest five times as quickly as possible. The total time elapsed for completing the five repetitions is recorded in seconds |
| Handgrip strength | Baseline; End of program (6-month); Follow up (12-month; 24-month) | Handgrip strength will be measured by a standard dynamometer. Peak value in kg for both arms will be collected |
| Magnetic Resonance Imaging (MRI) | Baseline and 6 months | Blood Oxygenation Level-Dependent (BOLD) Signal will be collected through functional MRI executed according to the published standards |
| Safety and tolerability | End of treatment (6-month) | Number of participants with treatment-related adverse events as assessed by the CTCAE version 4.0 |
| Long-term survival rate assessment | Baseline, end of treatment (6-month); follow up (12-month); follow up (18-month); Follow up (24-month); Follow up (36-month) | Long-term survival rate All-cause mortality of the enrolled patients will be checked from the regional's datasets. In case of positive findings, the days elapsed from enrollment to the event will be recorded for additional analyses, as well as the reasons and the diagnoses. |
| Long-term hospitalizations assessment | Baseline, end of treatment (6-month); follow up (12-month); follow up (18-month); Follow up (24-month); Follow up (36-month) | Long-term hospitalizations All-cause hospitalization will be checked from the regional's datasets. In case of positive findings, the days elapsed from enrollment to the event will be recorded for additional analyses, as well as the reasons and the diagnoses. |
| Body mass index assessment | Baseline, end of the program (6-month); follow up (12-month; 24-month) | Body mass index Body composition will be assessed with direct measures of height and weight. Body mass index will be calculated as the ratio between weight (in kg) and the squared height (in meters) |
Countries
France, Italy, Lithuania, Netherlands, Poland, Switzerland
Contacts
Primary ContactCrmine Zoccali
Outcome results
None listed