Ignite Creation Date:
2024-05-06 @ 3:31 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04664426
Status:
COMPLETED
Last Update Posted:
2023-06-29
First Post:
2020-11-16
Brief Title:
Sensory Neuropathy Scores Validated by Quantitative Sensory Testing and Nerve Conduction Studies for Kidney Transplant Recipients
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Adapted Modified Toronto Clinical Neuropathy Score and Erasmus Polyneuropathy Symptom Score Validated by Quantitative Sensory Testing and Nerve Conduction Studies for Kidney Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2023-06
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:
SENS
Brief Summary:
Sensory polyneuropathy is one of the most prevalent neurological disorders and a common finding in kidney transplant recipients KTR However prevalence course and underlying aetiology in this specific patient group remain unexplored To diagnose sensory polyneuropathy in KTR in clinical practice a relatively easy and inexpensive method is needed The Erasmus Polyneuropathy Symptom Score E-PSS and the adapted modified Toronto Clinical Neuropathy Score amTCNS are such scores These scores would enable internal medicine physicians to diagnose polyneuropathy in a reliable way without the need of additional examinations However a validation of the E-PSS and amTCNS with the golden standard of diagnosing sensory polyneuropathy which are quantitative sensory testing QST and nerve conduction studies NCS is needed
The objective of this observational cross-sectional study is to validate the E-PSS and amTCNS with QST and NCS and to determine reference values of the amTCNS 200 KTR will be included to take part in one study visit which encompasses neurological examination according to the protocol of the amTCNS QST and NCS Prior to the study visit participants will be asked to answer the E-PSS questionnaire in the home setting
The main study endpoint is to validate the E-PSS and the amTCNS result with QST and NCS To reach this endpoint different study parameters will be included which are the result of the E-PSS and amTCNS results of the QST thermal threshold testing and results of the NCS amplitude velocity and distal latency of measurements at the sural sensory nerve ulnar sensory nerve peroneal motor nerve tibial motor nerve and ulnar motor nerve soleus H reflex
The objective of this observational cross-sectional study is to validate the E-PSS and amTCNS with QST and NCS and to determine reference values of the amTCNS 200 KTR will be included to take part in one study visit which encompasses neurological examination according to the protocol of the amTCNS QST and NCS Prior to the study visit participants will be asked to answer the E-PSS questionnaire in the home setting
The main study endpoint is to validate the E-PSS and the amTCNS result with QST and NCS To reach this endpoint different study parameters will be included which are the result of the E-PSS and amTCNS results of the QST thermal threshold testing and results of the NCS amplitude velocity and distal latency of measurements at the sural sensory nerve ulnar sensory nerve peroneal motor nerve tibial motor nerve and ulnar motor nerve soleus H reflex
Detailed Description:
Sensory polyneuropathy is one of the most prevalent neurological disorders A Dutch study observed an incidence of all types of polyneuropathy of 77 per 100000 person-years which increases with age Besides previous studies evaluated the impact of polyneuropathy on quality of life in different patient populations and showed that accompanying symptoms affect daily living and influence morbidity and mortality of patients adversely
We can classify sensory polyneuropathies broadly into either small fibre neuropathies large fibre neuropathies or mixed small and large fibre neuropathies In small fibre neuropathies the thinly myelinated A delta and unmyelinated C fibres are affected Therefore the transmission of thermal and noxious sensory input is disturbed translating to symptoms of sharp painful or burning paraesthesia sensory loss or numbness and the inability to discriminate between hot and cold sensation Disorders affecting the large myelinated A delta fibres lead to an impaired vibration sensation and proprioception Patients will complain about a combination of symptoms of sensory loss paraesthesia and gait imbalance
Sensory polyneuropathy is a common finding in kidney transplant recipients KTR but little is known about prevalence course or underlying aetiology in this specific group It is known that patients are at a high risk to develop polyneuropathy before kidney transplantation due to chronic kidney disease Therefore related to the previous state of chronic kidney disease uremic and diabetic polyneuropathy are probable underlying aetiologies in KTR Furthermore the use of immunosuppressive medication after transplantation in particular tacrolimus may result in polyneuropathic symptoms and signs These circumstances may explain the high prevalence of polyneuropathy in KTR but in order to gain more understanding it is necessary to diagnose and stage polyneuropathy in an easy and convenient way in KTR Furthermore early diagnosis and treatment of certain types of polyneuropathy can prevent further worsening of neuropathic symptoms and signs or even reverse the neurologic deficits
The diagnostic approach to polyneuropathy differs depending on the type of affected nerve fibre and the distribution of nerve damage in the respective type of polyneuropathy The diagnosis of polyneuropathy is generally based on the presence of distal sensory and sensorimotor symptoms and signs and loss of function which is consistent with the clinical picture Nevertheless to reveal an underlying large fibre aetiology nerve conduction studies NCS are needed With the help of NCS it is possible to categorize polyneuropathy as primary axonal or primary demyelinating This standard diagnostic test however exclusively enables the measurement of large fibres and patients with pure small fibre neuropathies will not show any nerve conduction abnormalities Hence quantitative sensory testing QST is required to assess the function of small sensory nerve fibres However NCS and QST are time-consuming fairly expensive and the investigator needs a certain level of expertise Alternatively different clinical scores exist that aim to detect and stage polyneuropathy based on symptoms and signs The Toronto Clinical Neuropathy Score TCNS was designed for diabetic sensorimotor polyneuropathy but it was shown that its usefulness extends beyond diabetic polyneuropathy These results were based on correlations of the TCNS with clinical electrophysiological and disability parameters in non-diabetic polyneuropathies The same study confirmed that reliability and accuracy were excellent Eventually the TCNS was modified into the mTCNS to better capture a scale of simple sensory tests representative of early-stage dysfunction and reflex testing was removed due to its high inter-rater variability The mTCNS was demonstrated to maintain an acceptable correlation with the precursor score In the University Medical Center Groningen UMCG a large population of KTR is followed within the scope of the TransplantLines cohort study and biobank For this purpose the mTCNS was further adapted by omitting testing of temperature sense due to practical reasons adapted into the amTCNS The E-PSS was designed to diagnose chronic polyneuropathy and was previously validated in a cohort of patients with chronic idiopathic axonal polyneuropathy
To be able to study prevalence course and underlying aetiology in this specific population of KTR it is crucial to reveal whether the E-PSS and amTCNS correlate with the golden standards of diagnosing polyneuropathy NCS and QST In the long term both clinical scores have great potential to help clinicians from various disciplines without the specific expertise needed for NCS and QST to diagnose polyneuropathy
In conclusion the aim of this research proposal is to validate the E-PSS and amTCNS with NCS and QST for a population of KTR
The primary objective is to validate the Erasmus Polyneuropathy Symptoms Score E-PSS and adapted modified Toronto Clinical Neuropathy Score amTCNS with QST and NCS
The secondary objective is to define reference values of the amTCNS dependent on predictors in a healthy subject population This healthy subject population consists of potential kidney donors that were already seen and examined within the TransplantLines cohort study and biobank prior to this study These healthy subjects will not undergo QST or NCS
This research protocol contains a cross-sectional study or can alternatively be described as a validation study The aim is to examine the validity of the E-PSS and amTCNS clinical scores that were designed to capture symptoms and signs of sensory polyneuropathy The E-PSS and amTCNS will be validated with QST and NCS which are defined as golden standards for diagnosing small fibre neuropathies and large fibre neuropathies respectively
The aim is to validate the E-PSS and amTCNS for a population of KTR to be able to subsequently identify and follow up on polyneuropathies in this specific population in a more convenient way
KTR will be recruited retrospectively after their participation in the TransplantLines cohort and biobank study in the UMCG by telephone Every possible future participant will receive written information concerning this study aim design and duration of the study disadvantages and risks of participation The subjects will be required to sign the written informed consent form within two weeks if they want to take part in this study The subjects will be informed that if they give consent for participation in the study they may withdraw consent at any time This withdrawal of consent may be given to the investigator in oral or written form After receiving the written informed consent a screening via telephone will be planned to assess whether the potential participant meets the inclusion criteria
The amTCNS result will be calculated based on a questionnaire and neurological examination This includes a symptoms score assessing foot pain numbness tingling weakness ataxia and upper limb symptoms and a sensory test score including testing of pinprick sensation light touch proprioception and vibration sense QST consists of thermal threshold testing in which the thresholds of warm sensation and cold sensation will be determined following the method of limits and the method of levels NCS will include testing of the CMAP amplitude and distal motor latency of the tibial peroneal and ulnar nerve the SNAP amplitude of the sural and ulnar nerve nerve conduction velocity and the soleus H-reflex Participants will be asked to fill in the questionnaire of the E-PSS prior to their study visit via mail
Prior to this study the amTCNS was already carried out in 200 healthy subjects which were potential kidney donors Clinical characteristics that function as independent predictors of the amTCNS in a healthy subject population will be determined by means of ordinal logistic regression analyses The 95th percentile of the amTCNS final score will be calculated to define reference values according to the identified independent predictors The outcome of the polyneuropathy measures of the current study will be dichotomized as follows presence of polyneuropathy both aberrant QST and NCS presence of small fibre neuropathy aberrant QST presence of large fibre neuropathy aberrant NCS These outcomes will be opposed to the dichotomous outcome of presence of polyneuropathy according to the reference value of the amTCNS that was previously established in a healthy subject population Sensitivity specificity positive predictive value and negative predictive value will be calculated
To compare amTCNS cut-off points for diagnosis the reference values determined in the cohort of healthy subjects without polyneuropathy will be compared with the data in KTR The accuracy of the amTCNS in KTR will be determined by the area under the receiver operating characteristic curve with the presence of polyneuropathy as the dichotomous outcome variable and amTCNS as the test The optimal diagnostic threshold will be identified by the point on the receiver operating characteristic curve closest to the point of perfect discrimination
We can classify sensory polyneuropathies broadly into either small fibre neuropathies large fibre neuropathies or mixed small and large fibre neuropathies In small fibre neuropathies the thinly myelinated A delta and unmyelinated C fibres are affected Therefore the transmission of thermal and noxious sensory input is disturbed translating to symptoms of sharp painful or burning paraesthesia sensory loss or numbness and the inability to discriminate between hot and cold sensation Disorders affecting the large myelinated A delta fibres lead to an impaired vibration sensation and proprioception Patients will complain about a combination of symptoms of sensory loss paraesthesia and gait imbalance
Sensory polyneuropathy is a common finding in kidney transplant recipients KTR but little is known about prevalence course or underlying aetiology in this specific group It is known that patients are at a high risk to develop polyneuropathy before kidney transplantation due to chronic kidney disease Therefore related to the previous state of chronic kidney disease uremic and diabetic polyneuropathy are probable underlying aetiologies in KTR Furthermore the use of immunosuppressive medication after transplantation in particular tacrolimus may result in polyneuropathic symptoms and signs These circumstances may explain the high prevalence of polyneuropathy in KTR but in order to gain more understanding it is necessary to diagnose and stage polyneuropathy in an easy and convenient way in KTR Furthermore early diagnosis and treatment of certain types of polyneuropathy can prevent further worsening of neuropathic symptoms and signs or even reverse the neurologic deficits
The diagnostic approach to polyneuropathy differs depending on the type of affected nerve fibre and the distribution of nerve damage in the respective type of polyneuropathy The diagnosis of polyneuropathy is generally based on the presence of distal sensory and sensorimotor symptoms and signs and loss of function which is consistent with the clinical picture Nevertheless to reveal an underlying large fibre aetiology nerve conduction studies NCS are needed With the help of NCS it is possible to categorize polyneuropathy as primary axonal or primary demyelinating This standard diagnostic test however exclusively enables the measurement of large fibres and patients with pure small fibre neuropathies will not show any nerve conduction abnormalities Hence quantitative sensory testing QST is required to assess the function of small sensory nerve fibres However NCS and QST are time-consuming fairly expensive and the investigator needs a certain level of expertise Alternatively different clinical scores exist that aim to detect and stage polyneuropathy based on symptoms and signs The Toronto Clinical Neuropathy Score TCNS was designed for diabetic sensorimotor polyneuropathy but it was shown that its usefulness extends beyond diabetic polyneuropathy These results were based on correlations of the TCNS with clinical electrophysiological and disability parameters in non-diabetic polyneuropathies The same study confirmed that reliability and accuracy were excellent Eventually the TCNS was modified into the mTCNS to better capture a scale of simple sensory tests representative of early-stage dysfunction and reflex testing was removed due to its high inter-rater variability The mTCNS was demonstrated to maintain an acceptable correlation with the precursor score In the University Medical Center Groningen UMCG a large population of KTR is followed within the scope of the TransplantLines cohort study and biobank For this purpose the mTCNS was further adapted by omitting testing of temperature sense due to practical reasons adapted into the amTCNS The E-PSS was designed to diagnose chronic polyneuropathy and was previously validated in a cohort of patients with chronic idiopathic axonal polyneuropathy
To be able to study prevalence course and underlying aetiology in this specific population of KTR it is crucial to reveal whether the E-PSS and amTCNS correlate with the golden standards of diagnosing polyneuropathy NCS and QST In the long term both clinical scores have great potential to help clinicians from various disciplines without the specific expertise needed for NCS and QST to diagnose polyneuropathy
In conclusion the aim of this research proposal is to validate the E-PSS and amTCNS with NCS and QST for a population of KTR
The primary objective is to validate the Erasmus Polyneuropathy Symptoms Score E-PSS and adapted modified Toronto Clinical Neuropathy Score amTCNS with QST and NCS
The secondary objective is to define reference values of the amTCNS dependent on predictors in a healthy subject population This healthy subject population consists of potential kidney donors that were already seen and examined within the TransplantLines cohort study and biobank prior to this study These healthy subjects will not undergo QST or NCS
This research protocol contains a cross-sectional study or can alternatively be described as a validation study The aim is to examine the validity of the E-PSS and amTCNS clinical scores that were designed to capture symptoms and signs of sensory polyneuropathy The E-PSS and amTCNS will be validated with QST and NCS which are defined as golden standards for diagnosing small fibre neuropathies and large fibre neuropathies respectively
The aim is to validate the E-PSS and amTCNS for a population of KTR to be able to subsequently identify and follow up on polyneuropathies in this specific population in a more convenient way
KTR will be recruited retrospectively after their participation in the TransplantLines cohort and biobank study in the UMCG by telephone Every possible future participant will receive written information concerning this study aim design and duration of the study disadvantages and risks of participation The subjects will be required to sign the written informed consent form within two weeks if they want to take part in this study The subjects will be informed that if they give consent for participation in the study they may withdraw consent at any time This withdrawal of consent may be given to the investigator in oral or written form After receiving the written informed consent a screening via telephone will be planned to assess whether the potential participant meets the inclusion criteria
The amTCNS result will be calculated based on a questionnaire and neurological examination This includes a symptoms score assessing foot pain numbness tingling weakness ataxia and upper limb symptoms and a sensory test score including testing of pinprick sensation light touch proprioception and vibration sense QST consists of thermal threshold testing in which the thresholds of warm sensation and cold sensation will be determined following the method of limits and the method of levels NCS will include testing of the CMAP amplitude and distal motor latency of the tibial peroneal and ulnar nerve the SNAP amplitude of the sural and ulnar nerve nerve conduction velocity and the soleus H-reflex Participants will be asked to fill in the questionnaire of the E-PSS prior to their study visit via mail
Prior to this study the amTCNS was already carried out in 200 healthy subjects which were potential kidney donors Clinical characteristics that function as independent predictors of the amTCNS in a healthy subject population will be determined by means of ordinal logistic regression analyses The 95th percentile of the amTCNS final score will be calculated to define reference values according to the identified independent predictors The outcome of the polyneuropathy measures of the current study will be dichotomized as follows presence of polyneuropathy both aberrant QST and NCS presence of small fibre neuropathy aberrant QST presence of large fibre neuropathy aberrant NCS These outcomes will be opposed to the dichotomous outcome of presence of polyneuropathy according to the reference value of the amTCNS that was previously established in a healthy subject population Sensitivity specificity positive predictive value and negative predictive value will be calculated
To compare amTCNS cut-off points for diagnosis the reference values determined in the cohort of healthy subjects without polyneuropathy will be compared with the data in KTR The accuracy of the amTCNS in KTR will be determined by the area under the receiver operating characteristic curve with the presence of polyneuropathy as the dichotomous outcome variable and amTCNS as the test The optimal diagnostic threshold will be identified by the point on the receiver operating characteristic curve closest to the point of perfect discrimination
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