Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06325878
Status:
RECRUITING
Last Update Posted:
2024-03-26
First Post:
2024-03-16
Brief Title:
Genetic Architecture of Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Sponsor:
Istituto Clinico Humanitas
Organization:
Istituto Clinico Humanitas
Study Overview
Official Title:
Dissecting the Genetic Architecture of Chronic Inflammatory Demyelinating Polyradiculoneuropathy CIDP
Status:
RECRUITING
Status Verified Date:
2024-03
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:
GEARCIDP
Brief Summary:
The objective of this study is to characterize the genetic architecture of a large cohort of CIDP patients to evaluate whether specific alleleshaplotypes are implicated in the risk of CIDP in its clinical and immunological variability severity therapeutic response and association with diabetes and other autoimmune diseases We will genotype 700000 single nucleotide polymorphisms SNPs by using the Illumina Global Screening Array GSA of approximately 1000 patients with CIDP About 3500 healthy controls from the Italian population have been already genotyped using GWAS from our genetic department Alleleshaplotypes will be also compared between patients with typical CIDP and its variants between CIDP patients with and without specific antibodies between CIDP patients with and without comorbidities between CIDP patients with low and high levels of disability and between CIDP patients with and without response to each individual treatment IVIg steroids plasma exchange
Detailed Description:
1 Specific aim 1 Characterize the genetic architecture of CIDP by using a genome-wide association study GWAS approach in a large cohort of CIDP patients and healthy controls thus defining the 1 Specific aim 1 Characterize the genetic architecture of CIDP by using a genome-wide association study GWAS approach in a large cohort of CIDP patients and healthy controls thus defining the spectrum of single common variants or their combinations in terms of haplotypes or risk score predisposing to the disease
Hypothesis The frequency of specific alleleshaplotypes in patients with CIDP is significantly different compared to that of the general population
Approach We will genotype 700000 single nucleotide polymorphisms SNPs by using the Illumina Global Screening Array GSA of approximately 1000 patients with CIDP About 3500 healthy controls from the Italian population have been already genotyped using GWAS from our genetic department Prof Asselta Humanitas Research Institute Milan
2 Specific aim 2 Explore the role of specific alleleshaplotypes in determining the clinical and immunological variability severity and therapeutic response of CIDP
Hypothesis The genetic architecture of patients with typical CIDP is -at least in part- distinct from that of the CIDP variants specific alleleshaplotypes associate with intermediate phenotypes such as the presence of antibodies anti-NF155 anti-NF186 CNTN1 anti-gangliosides Specific alleleshaplotypes correlate with severity and treatment-response of CIDP
Approach Alleleshaplotypes evidence through GWAS will be compared between patients with typical CIDP and its variants between CIDP patients with and without specific antibodies between CIDP patients with low and high levels of disability and between CIDP patients with and without response to each individual treatment IVIg steroids plasma exchange in order to determine whether genetics play a role in determining these phenotypes
3 Specific aim 3 Verify possible overlaps between CIDP and other autoimmune diseases
Hypothesis Alleleshaplotypes identified through GWAS play a role in the increased risk of diabetes and other autoimmune disease in CIDP
Approach Alleleshaplotypes evidence through GWAS will be compared between CIDP patients with and without diabetes mellitus and with and without any other autoimmune diseases
This is a multicenter international observational study where a large number of CIDP patients will be screened using GWAS About 3500 healthy controls from the Italian population have been already genotyped using GWAS Patients with a diagnosis of CIDP according to the current diagnostic criteria will be included Patients with autoimmune nodopathies will be also included Patients must give informed consent to participate For all the patients the diagnosis at enrollment will be revised by the coordinating Center according to the European Academy of NeurologyPeripheral Nerve Society EANPNS diagnostic criteria
All included patients will undergo a detailed clinical history including time of clinical onset presence - distribution and date of onset of motor and sensory symptoms ataxia pain tremor cramps fatigue autonomic dysfunction and cranial nerve involvement using a specific questionnaire This information will be integrated with the data reported in the medical records Disease course will be defined as progressive relapsing or monophasic by the treating neurologist The clinical evaluation at enrolment will include assessment of muscle strength using the Medical Research Council MRC sumscore on 12 muscles range 0-60 Neurological disability will be evaluated at enrollment with the Inflammatory-Rash Overall Built Disability Scale I-RODS and the Inflammatory Neuropathy Cause and Treatment INCAT disability scale while Quality of life QoL will be assessed with the EuroQol-5D-3L scale Response to treatment will be defined as a subjective improvement that was objectively confirmed by I-RODS 4 centile points or INCAT disability scale 1 point or MRC sum score 0-60 2-4 points or grip strength using Martin Vigorimeter 8 -14 kPa6 Results of previously performed examinations including cerebrospinal fluid CSF analysis nerve ultrasound or brachiallumbosacral plexus MR magnetic resonance examination and sural nerve biopsy will be included when available The results of nerve conduction studies performed during the course of the disease will be included Sensory nerve conduction studies will be performed bilaterally in median ulnar and sural nerves and included evaluation of sensory nerve action potential amplitude distal latency and sensory conduction velocity Motor nerve conduction studies will be also performed bilaterally in median ulnar common peroneal and tibial nerves and included distal and proximal compound muscle action potential amplitude and duration motor conduction velocity distal and proximal motor latency and in most patients F-wave latency Abnormalities of motor and sensory nerve conduction studies consistent with demyelination will be defined according to the EANPNS criteria In all the patients the diagnosis at entry will be revised by the coordinating Center according to the above-mentioned diagnostic criteria
Patients data will be shared under pseudonymised form using the patients code among the centres
Enrollment in the study will be offered to all patients included in the Italian CIDP database Enrollment will then be extended to other Italian and European centers
Hypothesis The frequency of specific alleleshaplotypes in patients with CIDP is significantly different compared to that of the general population
Approach We will genotype 700000 single nucleotide polymorphisms SNPs by using the Illumina Global Screening Array GSA of approximately 1000 patients with CIDP About 3500 healthy controls from the Italian population have been already genotyped using GWAS from our genetic department Prof Asselta Humanitas Research Institute Milan
2 Specific aim 2 Explore the role of specific alleleshaplotypes in determining the clinical and immunological variability severity and therapeutic response of CIDP
Hypothesis The genetic architecture of patients with typical CIDP is -at least in part- distinct from that of the CIDP variants specific alleleshaplotypes associate with intermediate phenotypes such as the presence of antibodies anti-NF155 anti-NF186 CNTN1 anti-gangliosides Specific alleleshaplotypes correlate with severity and treatment-response of CIDP
Approach Alleleshaplotypes evidence through GWAS will be compared between patients with typical CIDP and its variants between CIDP patients with and without specific antibodies between CIDP patients with low and high levels of disability and between CIDP patients with and without response to each individual treatment IVIg steroids plasma exchange in order to determine whether genetics play a role in determining these phenotypes
3 Specific aim 3 Verify possible overlaps between CIDP and other autoimmune diseases
Hypothesis Alleleshaplotypes identified through GWAS play a role in the increased risk of diabetes and other autoimmune disease in CIDP
Approach Alleleshaplotypes evidence through GWAS will be compared between CIDP patients with and without diabetes mellitus and with and without any other autoimmune diseases
This is a multicenter international observational study where a large number of CIDP patients will be screened using GWAS About 3500 healthy controls from the Italian population have been already genotyped using GWAS Patients with a diagnosis of CIDP according to the current diagnostic criteria will be included Patients with autoimmune nodopathies will be also included Patients must give informed consent to participate For all the patients the diagnosis at enrollment will be revised by the coordinating Center according to the European Academy of NeurologyPeripheral Nerve Society EANPNS diagnostic criteria
All included patients will undergo a detailed clinical history including time of clinical onset presence - distribution and date of onset of motor and sensory symptoms ataxia pain tremor cramps fatigue autonomic dysfunction and cranial nerve involvement using a specific questionnaire This information will be integrated with the data reported in the medical records Disease course will be defined as progressive relapsing or monophasic by the treating neurologist The clinical evaluation at enrolment will include assessment of muscle strength using the Medical Research Council MRC sumscore on 12 muscles range 0-60 Neurological disability will be evaluated at enrollment with the Inflammatory-Rash Overall Built Disability Scale I-RODS and the Inflammatory Neuropathy Cause and Treatment INCAT disability scale while Quality of life QoL will be assessed with the EuroQol-5D-3L scale Response to treatment will be defined as a subjective improvement that was objectively confirmed by I-RODS 4 centile points or INCAT disability scale 1 point or MRC sum score 0-60 2-4 points or grip strength using Martin Vigorimeter 8 -14 kPa6 Results of previously performed examinations including cerebrospinal fluid CSF analysis nerve ultrasound or brachiallumbosacral plexus MR magnetic resonance examination and sural nerve biopsy will be included when available The results of nerve conduction studies performed during the course of the disease will be included Sensory nerve conduction studies will be performed bilaterally in median ulnar and sural nerves and included evaluation of sensory nerve action potential amplitude distal latency and sensory conduction velocity Motor nerve conduction studies will be also performed bilaterally in median ulnar common peroneal and tibial nerves and included distal and proximal compound muscle action potential amplitude and duration motor conduction velocity distal and proximal motor latency and in most patients F-wave latency Abnormalities of motor and sensory nerve conduction studies consistent with demyelination will be defined according to the EANPNS criteria In all the patients the diagnosis at entry will be revised by the coordinating Center according to the above-mentioned diagnostic criteria
Patients data will be shared under pseudonymised form using the patients code among the centres
Enrollment in the study will be offered to all patients included in the Italian CIDP database Enrollment will then be extended to other Italian and European centers
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