Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06379594
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-04-23
First Post:
2024-03-14
Brief Title:
UK Based Remote Brain Health Clinic BHC for Patients With Mild Cognitive Impairment MCI
Sponsor:
South London and Maudsley NHS Foundation Trust
Organization:
South London and Maudsley NHS Foundation Trust
Study Overview
Official Title:
Feasibility And Acceptability of a UK Based Remote Brain Health Clinic For Patients With Mild Cognitive Impairment MCI
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-04
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:
BHC
Brief Summary:
This project aims to understand the feasibility acceptability and real-world evidence of a novel UK-based remote brain health clinic for patients with mild cognitive impairment MCI A timely and accurate diagnosis of dementia is a priority in the UK and MCI is indicative of future risk of cognitive decline An accurate etiological diagnosis of MCI MCI-subtyping - distinguishing those who are likely to go on to develop dementia and those who are not is vital for treatment planning Whilst the assessment of molecular biological markers biomarkers for etiological diagnosis of MCI and Alzheimers disease AD is increasingly recommended and employed internationally the uptake is low in UK memory clinics The Brain Health Clinic BHC has been specifically designed as a state-of-the-art diagnostic centre for those with MCI Procedures will include a range of clinical and biomarker assessments with molecular biomarkers based on lumbar puncture and cerebrospinal fluid CSF analysis Additionally the clinic will employ remote neuropsychiatric assessments using digital and telephonic methods This allows for regular contact whilst adhering to changes in clinical practice and national guidance due to the COVID-19 pandemic Our overarching objectives are to first establish the acceptability and feasibility of the remote Brain Health Clinic and its novel clinical and biomarker assessment programme Then secondly establish the impact of care under the Brain Health Clinic on i care management decisions eg follow-up and treatment planning ii time to etiological diagnosis of MCI MCI-subtyping and iii time to diagnosis of dementia and severity of dementia at the time of diagnosis
Detailed Description:
The Brain Health Clinic is designed to complement the existing memory clinic pathway and will complete the patient journey of patients with mild cognitive impairment MCI All patients referred to the new brain health clinic will be assessed using a standardized battery of clinical instruments by qualified clinicians as per South London and Maudsley SlaM memory clinic pathway In line with clinical practice changes and national guidance due to the COVID-19 pandemic these assessments will be completed remotely via telephone andor video conferencing and online
Consenting participants will be invited to complete the Brain health Clinics initial assessments All assessments will be completed remotely Assessments will include cognitive assessments such as Telephone Interview for Cognitive Status Modified version 39 TICS-M v39 the Clinical Dementia Rating Scale Sum of Boxes CDR-SoB for telephone consultations Computerised Integrated Cognitive Assessment ICA-comp The Hospital Anxiety and Depression HADS will be used to assess the symptoms of anxiety and depression For the information from participants carersstudy partners the following questionnaires will used Amsterdam Instrumental Activities of Daily Living Questionnaire A-IADL-Q Informant Questionnaire on Cognitive Decline in the Elderly IQCODE Adult Carer Quality of Life Questionnaire AC-QoL and Neuropsychiatric Inventory-Questionnaire NPI-Q Assessment battery can be completed in more than one session as required Participants will be given the opportunity to complete self-assessments such as HADS in their own time prior to the first assessment session
Participants will be reviewed in the clinic at baseline 6 and 12 months A biomarker program consisting of lumbar puncture with cerebral spinal fluid CSF analysis following international guidelines Engelborghs et al 2017 saliva sampling and electroencephalogram EEG will be applied to every consenting participant This will be completed within two months of baseline assessment A safety questionnaire for lumbar puncture will be administered to ensure eligibility for the procedure The lumbar puncture facilities will be located in the BRC Clinical Research Facility The CSF samples collected from the lumbar puncture will be shipped to Affinity Biomarker Labs where the analysis will be conducted using a Cobas 6000 analyser for three assays Elecsys β-Amyloid1-42 CSF Elecsys Phospho-Tau 181P CSF Elecsys Total -Tau CSF Consented samples for future studies will undergo centrifugation transfer to new tubes aliquoting into cryovials and storage at -80 degrees Fahrenheit
Saliva samples will be analysed by Cytox Group Limited who will employ a polygenic risk scoring algorithm genoSCORE-LAB to identify those at the highest genetic risk of cognitive decline and Alzheimers disease using genetic data from the saliva sample Daunt P et al 2020 EEG will also be offered as an optional investigation to help support the diagnostic process The EEG will be acquired by a trained researcher or neurophysiologist
The consented participants will also be seen by a phlebotomy trained study researcher who will take blood plasma samples and store them at -80 degrees Fahrenheit
As per clinic guidance participants with negative CSF biomarker results indicating that their MCI is unlikely to progress to dementia will be discharged from the brain health clinic back to their General Practitioners GP and so will not complete the 6- and 12-month assessments They will however complete all appropriate feedback questionnaires and a sub-sample will be invited to participate in a semi-structured interview to further explore their experiences of the remote brain health clinic The interview will be conducted remotely by telephonevideo conferencing Questionnaires will be administered to participants concerning the feasibility and acceptability of i the brain health clinic itself and ii the following brain health clinic procedures lumbar puncture saliva sampling EEG ICA-comp assessment and CDR-SoB assessment Additionally carersstudy partners will be asked to complete a questionnaire concerning their views on the acceptability and feasibility of the brain health clinic The time from the first assessment until the final diagnosis will be recorded as well as diagnostic confidence and the plan for future monitoring outlining the determinants for continued monitoring vs discharge to GP A subsample of 12 participants will be invited to participate in a semi-structured interview to further explore their experiences of the remote brain health clinic The interview will be conducted remotely by telephonevideo conferencing The interviews will be audio recorded with participants39 consent and will be transcribed Thematic analysis will be completed supported by Nvivo software Qsr International 2012 Magnetic resonance imaging MRIdata obtained as part of the memory service or Brain Health Clinic pathway will be analysed in order to establish the predictive validity of BrainageR software and automated volumetric measures in reference to a normative population Novel AI and machine learning tools will also be applied to MRI scans alongside existing biomarkers No MRI scans will be carried out as part of this study Historical MRI scans will be retrospectively analysed Historical data on patients receiving MCI and dementia diagnoses will be obtained from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre SLaM BRC Clinical Record Interactive Search CRIS resource The CRIS system allows research access to the anonymized electronic health record of one of Europes specialist dementia care provider and currently data are available for 20000 patients with dementia and more than 3000 patients with MCI
The data source has been enhanced through more than 100 natural language processing algorithms facilitating the extraction of in-depth data from free text including the degree of cognitive impairment at MCI and dementia diagnosis Couch et al 2021 This source will be utilized to identify patients referred to SLAM memory clinics who have been diagnosed with MCI approximately 10 The objectives are to determine 1 the time from discharge from the memory clinic with MCI diagnosis to a new referral and dementia diagnosis and 2 the severity of dementia at the time of diagnosis
A sub-study involving a programme of cognitive training games will be offered to a maximum subset of 30 participants The games target episodic memory semantic and spatial abilities and working memory Participants will train 5 days per week for 10 weeks Each training session lasts 24 min ie participants will play 3 games per session each for 8 min
The Quality assurance The monitoring of this trial to ensure compliance with Good Clinical Practice and scientific integrity will be managed by the study team The research team will have quarterly meetings to monitor the conduct of the trail A proportion of research projects undertaken within the Institute of Psychiatry Psychology and Neuroscience Kings College London are selected at random and subjected to internal audit each year It is anticipated that no further monitoring or auditing will be necessary however the Chief Investigator will be available to provide support with any situations that arise which have not been accounted for
Data Management and Monitoring
An electronic Case Report Form CRF will be used which will be stored in a password protected database which is stored on a password protected encrypted secure network Access to this document will be restricted to the Chief Investigator and clinical researchers Study progress and all other aspects of data monitoring will be completed by the Chief Investigator and research team Quarterly meetings will be held to facilitate this
Statistical analysis
The statistical analysis will mainly consist of descriptive analyses such as mean or median of scale scores with diversity measures Standard Deviation or Interquartile Range as appropriate or proportions with Confidence Interval Given the cross-sectional nature of the study significant drop-out is not anticipated however a 10 drop-out rate will be factored into the analysis An interim analysis is scheduled for completion at 12 months
Feedback questionnaires Acceptability of the brain health clinic and its procedures will be assessed from the perspective of participants via a series of short questionnaires that include both 5-point Likert scales and open-ended questions The likert scales will contain ordinal variables therefore nonparametric methods will be used to analyse the data collected the central tendency will be summarised by median or the mode calculations and dispersion summarised by the range across quartiles The qualitative information obtained by the open-ended questions will be manually coded and analysed by thematic analysis the software package NVivo will be utilised to support with this All coding and themes will be checked by a second researcher to ensure that no aspect of the data has been overrepresented Brain health clinic procedures will be considered acceptable if 70 of participants rate each aspect of acceptability explored as satisfactory or above Study partners will also complete a questionnaire concerning acceptability feasibility and clinical value of the brain health clinic The questionnaire will be analysed utilising the same methods as the participants questionnaires Participant semi-structured interviews Interviews will be audio recorded with participants consent and the results transcribed An inductive thematic analysis will be completed supported by Nvivo software Qsr International 2012 Braun and Clarkes six phase method for conducting a thematic analysis will be followed Braun ampamp Clarke 2006 Themes across the dataset will be checked by a researcher with qualitative experience who is independent of the initial analysis to ensure that no aspect of the data has been under or overrepresented Themes will be reported to inform any amendments or improvements to the brain health clinic
Lab analysis CSF - The following Assay system will be used to analyse CSF ElectroChemiLuminescence Immunoassay Instrument Cobas 6000 analyzer series The Assays are Elecsys β-Amyloid1-42 CSF Elecsys Phospho-Tau 181P CSF ampampampampampamp Elecsys Total -Tau CSF Saliva - Samples will be analysed by Cytox Group Limited who will employ a polygenic risk score algorithm genoSCORE-LAB to identify those at highest genetic risk of cognitive decline and Alzheimers disease using genetic data from the saliva sample genoSCORE-LAB is a genetic test that analyses patient genotypes generated from an array of 114000 single nucleotide polymorphisms - common genetic variations - that are associated with or protective against the risk of developing Alzheimers disease Blood plasma - Blood samples will be immediately centrifuged Plasma will be extracted from this sample and stored for future diagnostic dementia research studies subject to ethical review Sub-study data analysis Data will be analysed using frequentist and Bayesian analysis methods Variables of interest are the maximum level reached and learning slope in each game reaction times number of correct answers and omissioncommission errors
Consenting participants will be invited to complete the Brain health Clinics initial assessments All assessments will be completed remotely Assessments will include cognitive assessments such as Telephone Interview for Cognitive Status Modified version 39 TICS-M v39 the Clinical Dementia Rating Scale Sum of Boxes CDR-SoB for telephone consultations Computerised Integrated Cognitive Assessment ICA-comp The Hospital Anxiety and Depression HADS will be used to assess the symptoms of anxiety and depression For the information from participants carersstudy partners the following questionnaires will used Amsterdam Instrumental Activities of Daily Living Questionnaire A-IADL-Q Informant Questionnaire on Cognitive Decline in the Elderly IQCODE Adult Carer Quality of Life Questionnaire AC-QoL and Neuropsychiatric Inventory-Questionnaire NPI-Q Assessment battery can be completed in more than one session as required Participants will be given the opportunity to complete self-assessments such as HADS in their own time prior to the first assessment session
Participants will be reviewed in the clinic at baseline 6 and 12 months A biomarker program consisting of lumbar puncture with cerebral spinal fluid CSF analysis following international guidelines Engelborghs et al 2017 saliva sampling and electroencephalogram EEG will be applied to every consenting participant This will be completed within two months of baseline assessment A safety questionnaire for lumbar puncture will be administered to ensure eligibility for the procedure The lumbar puncture facilities will be located in the BRC Clinical Research Facility The CSF samples collected from the lumbar puncture will be shipped to Affinity Biomarker Labs where the analysis will be conducted using a Cobas 6000 analyser for three assays Elecsys β-Amyloid1-42 CSF Elecsys Phospho-Tau 181P CSF Elecsys Total -Tau CSF Consented samples for future studies will undergo centrifugation transfer to new tubes aliquoting into cryovials and storage at -80 degrees Fahrenheit
Saliva samples will be analysed by Cytox Group Limited who will employ a polygenic risk scoring algorithm genoSCORE-LAB to identify those at the highest genetic risk of cognitive decline and Alzheimers disease using genetic data from the saliva sample Daunt P et al 2020 EEG will also be offered as an optional investigation to help support the diagnostic process The EEG will be acquired by a trained researcher or neurophysiologist
The consented participants will also be seen by a phlebotomy trained study researcher who will take blood plasma samples and store them at -80 degrees Fahrenheit
As per clinic guidance participants with negative CSF biomarker results indicating that their MCI is unlikely to progress to dementia will be discharged from the brain health clinic back to their General Practitioners GP and so will not complete the 6- and 12-month assessments They will however complete all appropriate feedback questionnaires and a sub-sample will be invited to participate in a semi-structured interview to further explore their experiences of the remote brain health clinic The interview will be conducted remotely by telephonevideo conferencing Questionnaires will be administered to participants concerning the feasibility and acceptability of i the brain health clinic itself and ii the following brain health clinic procedures lumbar puncture saliva sampling EEG ICA-comp assessment and CDR-SoB assessment Additionally carersstudy partners will be asked to complete a questionnaire concerning their views on the acceptability and feasibility of the brain health clinic The time from the first assessment until the final diagnosis will be recorded as well as diagnostic confidence and the plan for future monitoring outlining the determinants for continued monitoring vs discharge to GP A subsample of 12 participants will be invited to participate in a semi-structured interview to further explore their experiences of the remote brain health clinic The interview will be conducted remotely by telephonevideo conferencing The interviews will be audio recorded with participants39 consent and will be transcribed Thematic analysis will be completed supported by Nvivo software Qsr International 2012 Magnetic resonance imaging MRIdata obtained as part of the memory service or Brain Health Clinic pathway will be analysed in order to establish the predictive validity of BrainageR software and automated volumetric measures in reference to a normative population Novel AI and machine learning tools will also be applied to MRI scans alongside existing biomarkers No MRI scans will be carried out as part of this study Historical MRI scans will be retrospectively analysed Historical data on patients receiving MCI and dementia diagnoses will be obtained from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre SLaM BRC Clinical Record Interactive Search CRIS resource The CRIS system allows research access to the anonymized electronic health record of one of Europes specialist dementia care provider and currently data are available for 20000 patients with dementia and more than 3000 patients with MCI
The data source has been enhanced through more than 100 natural language processing algorithms facilitating the extraction of in-depth data from free text including the degree of cognitive impairment at MCI and dementia diagnosis Couch et al 2021 This source will be utilized to identify patients referred to SLAM memory clinics who have been diagnosed with MCI approximately 10 The objectives are to determine 1 the time from discharge from the memory clinic with MCI diagnosis to a new referral and dementia diagnosis and 2 the severity of dementia at the time of diagnosis
A sub-study involving a programme of cognitive training games will be offered to a maximum subset of 30 participants The games target episodic memory semantic and spatial abilities and working memory Participants will train 5 days per week for 10 weeks Each training session lasts 24 min ie participants will play 3 games per session each for 8 min
The Quality assurance The monitoring of this trial to ensure compliance with Good Clinical Practice and scientific integrity will be managed by the study team The research team will have quarterly meetings to monitor the conduct of the trail A proportion of research projects undertaken within the Institute of Psychiatry Psychology and Neuroscience Kings College London are selected at random and subjected to internal audit each year It is anticipated that no further monitoring or auditing will be necessary however the Chief Investigator will be available to provide support with any situations that arise which have not been accounted for
Data Management and Monitoring
An electronic Case Report Form CRF will be used which will be stored in a password protected database which is stored on a password protected encrypted secure network Access to this document will be restricted to the Chief Investigator and clinical researchers Study progress and all other aspects of data monitoring will be completed by the Chief Investigator and research team Quarterly meetings will be held to facilitate this
Statistical analysis
The statistical analysis will mainly consist of descriptive analyses such as mean or median of scale scores with diversity measures Standard Deviation or Interquartile Range as appropriate or proportions with Confidence Interval Given the cross-sectional nature of the study significant drop-out is not anticipated however a 10 drop-out rate will be factored into the analysis An interim analysis is scheduled for completion at 12 months
Feedback questionnaires Acceptability of the brain health clinic and its procedures will be assessed from the perspective of participants via a series of short questionnaires that include both 5-point Likert scales and open-ended questions The likert scales will contain ordinal variables therefore nonparametric methods will be used to analyse the data collected the central tendency will be summarised by median or the mode calculations and dispersion summarised by the range across quartiles The qualitative information obtained by the open-ended questions will be manually coded and analysed by thematic analysis the software package NVivo will be utilised to support with this All coding and themes will be checked by a second researcher to ensure that no aspect of the data has been overrepresented Brain health clinic procedures will be considered acceptable if 70 of participants rate each aspect of acceptability explored as satisfactory or above Study partners will also complete a questionnaire concerning acceptability feasibility and clinical value of the brain health clinic The questionnaire will be analysed utilising the same methods as the participants questionnaires Participant semi-structured interviews Interviews will be audio recorded with participants consent and the results transcribed An inductive thematic analysis will be completed supported by Nvivo software Qsr International 2012 Braun and Clarkes six phase method for conducting a thematic analysis will be followed Braun ampamp Clarke 2006 Themes across the dataset will be checked by a researcher with qualitative experience who is independent of the initial analysis to ensure that no aspect of the data has been under or overrepresented Themes will be reported to inform any amendments or improvements to the brain health clinic
Lab analysis CSF - The following Assay system will be used to analyse CSF ElectroChemiLuminescence Immunoassay Instrument Cobas 6000 analyzer series The Assays are Elecsys β-Amyloid1-42 CSF Elecsys Phospho-Tau 181P CSF ampampampampampamp Elecsys Total -Tau CSF Saliva - Samples will be analysed by Cytox Group Limited who will employ a polygenic risk score algorithm genoSCORE-LAB to identify those at highest genetic risk of cognitive decline and Alzheimers disease using genetic data from the saliva sample genoSCORE-LAB is a genetic test that analyses patient genotypes generated from an array of 114000 single nucleotide polymorphisms - common genetic variations - that are associated with or protective against the risk of developing Alzheimers disease Blood plasma - Blood samples will be immediately centrifuged Plasma will be extracted from this sample and stored for future diagnostic dementia research studies subject to ethical review Sub-study data analysis Data will be analysed using frequentist and Bayesian analysis methods Variables of interest are the maximum level reached and learning slope in each game reaction times number of correct answers and omissioncommission errors
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