- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03382444
The Kidney and The Brain Study - Assessment of Cognitive Impairment in Advanced CKD
A Longitudinal Assessment of Cognitive Impairment in Advanced CKD Transitioning Into Renal Replacement Therapy
Patients with failed kidneys need Renal Replacement Therapy (RRT) to remove fluid and toxins from the body. The 3 types of RRT are kidney transplant or removal of waste by dialysis, either via the blood (haemodialysis) or via the stomach area (peritoneal dialysis). 27,000 patients currently receive dialysis in the UK and some endure reduced quality-of-life, depression, and thinking and memory difficulties. Some of these symptoms reflect undiagnosed dementia. Indeed up to 7/10 dialysis patients suffer moderate to severe brain impairment or dementia - much more frequently than in the general population.
This study will assess brain function just before starting dialysis/transplant and at 3 and 12 months afterwards with face to face assessments and with brain scans in some patients. Changes in brain function will be compared between people treated with the different forms of dialysis and transplant.
The Investigators hope to evaluate whether these tests are acceptable to patients, whether affected sub-groups with cognitive impairment can be identified early, and if certain dialysis methods are better for patients with cognitive impairment/dementia, so that a larger study to try to improve brain function after RRT can be developed.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Aims of the proposed research
Primary Objective:
To test the feasibility of performing serial detailed neurocognitive assessments in patients before during and after the period of commencing RRT for End-Stage Kidney Disease
Secondary Objectives:
- Estimate cross-sectional and longitudinal variability in a novel battery of neurocognitive assessments amongst participants in transition to all 3 modalities of RRT.
- Assess the administration, suitability and adherence of the chosen cognitive and quality of life measures in participants.
- Test the feasibility of recruitment to a longitudinal brain magnetic resonance imaging (MRI) study in a randomly selected proportion of participants.
- Estimate the cross-sectional and longitudinal variability in multiparametric brain MRI parameters and their interaction with cognitive functional change in this transitional population.
- To describe resource implications including patients referred to specialist services due to new diagnoses of cognitive impairment, dementia and/or depression
Study Design
This is a prospective study of 96 patients who are about to commence renal replacement therapy (RRT). Patients will undergo a neurocognitive, depression and quality of life assessments at baseline, 3 months after commencing RRT and 12 months after commencing RRT. A nested cohort of 25% will undergo MR brain scans at baseline and at 12 months.
Detailed Plan of Investigation
Recruitment procedure The target population is clinic based patients with advanced CKD who are due to commence RRT in the next 1-2 months as determined by the treating clinician. Patient screening, information giving and consenting for this feasibility study will be performed in the low clearance clinic at Salford (held twice per week). Enrolment of willing and eligible patients who are admitted into hospital to start RRT in the absence of infection and delirium may also be assessed.
Study Protocol Overall feasibility of the study will be assessed based on recruitment rates of eligible patients as well as consent rates, withdrawal rates, missing data and study costs. This data is also relevant to assess the feasibility of performing brain MR scans in this cohort. In addition, factors which may impact on cognitive function, such as age, gender, education, ethnicity and socioeconomic status, will be assessed at baseline to better inform future trial design.
Participants will undergo testing of all measures (except imaging) at baseline, 3 months after starting renal replacement therapy (RRT+3) and after 12 months (RRT+12). Baseline is defined as any participant whose eGFR is <15mls/min/1.73m2 and is expected to need to start renal replacement therapy within 2 months. An opportunistic sampling technique will be used. The research fellow will engage in multidisciplinary meetings that follow the low clearance clinics and will use these to identify potential participants, participants will then be contacted and if they demonstrate potential willingness to participate then will be sent the participant information sheet. Consent will then be taken and if the participant is expected to start RRT within 2 months then baseline assessments will occur at next clinic appointment.
Where participants transfer from one modality of dialysis to another the participants will be assigned to the modality of dialysis most frequently undertaken in the 3 months prior to testing. Assessment will be delayed when there has been a modality switch within the last 1 month of assessment date. Where a participant has received a renal transplant after commencing dialysis cognitive assessment will occur as near to the 3 and 12-month time point as possible. Where a participant receives a pre-emptive transplant (prior to any dialysis) then cognitive assessments will occur at 3 and 12 months post-transplant date.
Cognition Cognitive assessments will be performed by the research fellow in a quiet clinical room with refreshments made available to the participants. This methodology has been used previously. Family members or carers will not be present. The assessments may last up to 2 hours. The assessments will usually follow clinic appointments to minimise participant inconvenience. Due to fluctuations in cognition in the weekly haemodialysis cycle. Cognitive assessments will occur on non-dialysis days in participants undergoing haemodialysis. There are no known treatment related fluctuations in cognition in peritoneal dialysis and these participants will be assessed before or after routine clinic appointments. The neurocognitive tests will be a combination of previously used and validated tests (below) and specifically designed assessments by Professor Montaldi at University of Manchester. They will be designed to detect the expected defects in cognitive domains that are known to be present in CKD and dialysis patients. It will be probe into these defects with more thoroughness and sensitivity than has been undertaken in previous studies.
The MoCA is a one-page 30-point screening test of global cognitive function taking approximately 10 minutes to administer. There are 3 alternate forms in English designed to minimize practice effects in longitudinal studies. The MoCA will be used in this study primarily to allow comparison with the results of other studies in RRT. It will also permit the first longitudinal validation of the MoCA in the target group against our detailed neurocognitive battery.
The main standardised neurocognitive tests will include:
- IQ (WASI);
- Memory (Weschler Memory Scale, Doors and People, Rey Figure) subtests;
- Speed of processing, attention (TEA) and executive function subtests (Hayling and Brixton).
Detection of more subtle memory changes over time will be explored using a similar foils test designed by Montaldi and colleagues and used in an older population The neurocognitive battery will be especially optimised to avoid potential practice effects.
Anxiety and Depression There are complex interactions between anxiety, depression and cognition. This has also been demonstrated in a cohort of haemodialysis patients. The hospital anxiety and depression scale will be used to measure this confounding variable. It has been used in a similar fashion in other studies of similar patient populations. It takes the form of a questionnaire and takes 2-5 minutes to complete. A systematic review of this tool identified that a score of 8/21 was optimal for the balancing sensitivity and specificity of an accurate depression and anxiety diagnosis. Participants with newly diagnosed severe anxiety or depression will be referred onwards to our renal psychology teams and local mental health care providers as appropriate.
Quality of life Quality of life (QOL) is an important output of healthcare analyses with quality of life factoring into patient decisions on RRT modality choices. A meta analyses of healthcare related quality of life demonstrated that in-centre haemodialysis patients suffered most. However most studies are cross sectional and subject to ascertainment bias. This study will use KDQOL-36TM questionnaire. This is a purposely designed QOL instrument for patients on dialysis. Relevant questions will be used at month 0 and the whole instrument will be applied at month RRT+3 and RRT+12.
Magnetic Resonance brain imaging Clinicians need to identify which patients are susceptible to cognitive changes in the future. Similarly, our renal service user group identified dementia risk as a key patient concern. Neuroimaging at baseline will identify those with changes indicative of vulnerability to cognitive decline. Longitudinal MR changes will provide insight into mechanistic aetiology and will help clarify the link between brain structure and function.
The Investigators will use a state-of the art dementia imaging protocol in a randomly selected group of 25% participants. This protocol has been developed by Dr Parkes and others as part of the Dementia Platforms UK Imaging network. This includes measures of gross morphological structure from high resolution T1-weighted images, microstructural change from diffusion-weighted imaging and markers of microvascular disease from T2-weighted FLAIR imaging (to quantify white matter lesion volume), susceptibility-weighted imaging (to visualise microbleeds) and arterial spin labelling (ASL) (for cerebral blood flow images). These quantitative imaging measurements will provide insight into the mechanisms by which kidney disease impacts cognition, and may allow prediction of the progression of such impairment. In particular, ASL (a technique in which Dr Parkes is internationally renowned), will provide information on the metabolic state of the brain which may be altered in kidney disease. Advanced diffusion-weighted imaging will also provide a sensitive indicator of loss of neural density/structure. The imaging protocol will last for 45 minutes and studies will be carried out in the MR imaging facilities at Central Manchester University Hospital, using exactly the same protocol. MR imaging will be performed twice in each of these participants - first prior to commencement of RRT and within 1 month of the baseline cognitive assessment and then within1 month of the RRT +12 assessment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Greater Manchester
-
Salford, Greater Manchester, United Kingdom, M6 8HD
- Salford Royal NHS Foundation Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- eGFR <15/ml/min/1.73m2
- Aged 55 years and over
- Mental capacity to understand the study and give informed consent
Exclusion Criteria:
- Age <55 years
- Non-English speaking
- Patients known to have a psychiatric condition, including severe depression, bipolar affective disorder, severe anxiety, panic disorder, substance misuse or psychosis or previous severe head injury
- Contraindications to magnetic resonance imaging
- Patients who have chosen not to undergo dialysis treatment (conservative care).
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To test the feasibility of performing serial detailed neurocognitive assessments in patients before during and after the period of commencing RRT for End-Stage Kidney Disease
Time Frame: 2.5years
|
Number of patients eligible, no of patients consented, number of patients who underwent both baseline and longitudinal neurocognitive assessments
|
2.5years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Estimate cross-sectional and longitudinal variability in a novel battery of neurocognitive assessments amongst participants in transition to all 3 modalities of RRT.
Time Frame: 2.5years
|
Determine variability in global cognitive scores and domain specific scores at baseline and then longitudinal trajectories at RRT+3months and RRT+12months
|
2.5years
|
Assess the administration, suitability and adherence of the chosen cognitive and quality of life measures in participants.
Time Frame: 2.5 years
|
Number of patients who agree to undertake all cognitive assessments, quality of life assessments and depression assessments as a total of the number of patients who participate
|
2.5 years
|
Test the feasibility of recruitment to a longitudinal brain magnetic resonance imaging (MRI) study in a randomly selected proportion of participants.
Time Frame: 18 months
|
Number of patients who undergo MR brain scans at baseline and at RRT+12months as a proportion of patients eligible and patients who undergo cognitive assessment.
|
18 months
|
Estimate the cross-sectional and longitudinal variability in multiparametric brain MRI parameters and their interaction with cognitive functional change in this transitional population.
Time Frame: 2.5years
|
Quantitative imaging maps of microstructure (from diffusion-weighted images) and cerebral blood flow will be co-registered to the T1-weighted image and median values extracted from each region of interest, along with volumes from the T1-weighted image.
In addition, the number of microbleeds and the white matter lesion volume will be recorded.
|
2.5years
|
To describe resource implications including patients referred to specialist services due to new diagnoses of cognitive impairment, dementia and/or depression
Time Frame: 2,5 years
|
To record the number of patients who are referred for specialist assessment for their cognitive impairment and/or depression
|
2,5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: James Tollitt, MBcHB, Northern Care Alliance NHS Foundation Trust
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 17/233064-S
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Kidney Diseases
-
3-C Institute for Social DevelopmentUniversity of North Carolina, Chapel HillCompletedChronic Kidney Diseases | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Pediatric Kidney Disease | Chronic Kidney Disease stage3 | Chronic Kidney Disease Stage V | Chronic Kidney Disease, Stage IV (Severe) | Chronic Kidney Disease Stage 2 | Chronic Kidney Disease, Stage IUnited States
-
American Academy of Family PhysiciansUniversity of Colorado, Denver; National Institute of Diabetes and Digestive... and other collaboratorsCompletedChronic Kidney Disease | Chronic Renal Insufficiency | Chronic Kidney Insufficiency | Chronic Renal Diseases | Kidney Insufficiency, ChronicUnited States
-
Universiti Putra MalaysiaRecruitingChronic Kidney Diseases | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Chronic Kidney Disease stage3 | Chronic Kidney Disease Requiring Chronic DialysisMalaysia
-
Centre Hospitalier le MansLe Mans UniversiteWithdrawnFatigue | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage3 | Chronic Kidney Failure | Chronic Kidney Disease, Stage 4 (Severe)
-
National Taiwan University HospitalCompletedChronic Kidney Disease stage4 | Chronic Kidney Disease stage3 | Chronic Kidney Disease Stage 2 | Chronic Kidney Disease Stage 1Taiwan
-
Centre Hospitalier le MansLe Mans UniversiteRecruitingFatigue | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Chronic Kidney Disease Stage 3BFrance
-
University of WashingtonJohns Hopkins University; National Institute of Diabetes and Digestive and... and other collaboratorsRecruitingChronic Kidney Diseases | Acute Renal Failure | Acute Renal Injury | Acute Kidney Failure | Chronic Renal Insufficiency | Kidney Failure, Acute | Renal Insufficiency, Acute | Acute Renal Insufficiency | Acute Kidney Insufficiency | Renal Failure, Acute | Chronic Kidney Insufficiency | Chronic Renal Diseases | Kidney... and other conditionsUnited States
-
University of the State of Santa CatarinaUnknownKidney Diseases | Chronic Kidney Diseases | Hemodialysis | Chronic Renal Insufficiency | Renal Dialysis | Chronic Kidney Insufficiency | Chronic Renal DiseasesBrazil
-
Texas A&M UniversityWithdrawnChronic Kidney FailureUnited States
-
Lund UniversityBaxter Healthcare Corporation; Universidad de CórdobaCompletedEnd Stage Kidney Disease | Chronic Kidney Disease Requiring Chronic DialysisArgentina
Clinical Trials on Cognitive Assessment
-
Universidad de GranadaUnknownChronic Obstructive Pulmonary DiseaseSpain
-
Philippine Neurological AssociationSt. Luke's Medical Center, Philippines; University of Santo Tomas Hospital,... and other collaboratorsRecruitingCognitive Impairment | Dementia | Mild Cognitive ImpairmentPhilippines
-
University Hospital, LilleCompleted
-
Rigshospitalet, DenmarkAarhus University Hospital; University of Copenhagen; Center for Rehabilitation...RecruitingCerebral PalsyDenmark
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingLiver and Intrahepatic Bile Duct DisorderUnited States
-
University of Texas Southwestern Medical CenterCompleted
-
University Hospital, GhentCompletedAphasia, Acquired | Short-Term Memory ImpairmentBelgium
-
ANRS, Emerging Infectious DiseasesRecruiting
-
AdventHealth Translational Research InstituteDavos Alzheimer's CollaborativeRecruiting
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingSickle Cell AnemiaFrance