Ignite Creation Date:
2024-05-06 @ 7:51 PM
Last Modification Date:
2024-10-26 @ 3:15 PM
Study NCT ID:
NCT06161038
Status:
RECRUITING
Last Update Posted:
2023-12-15
First Post:
2023-12-05
Brief Title:
Precision Medicine for Nociception Sngception and Proprioception
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Precision Medicine for Nociception Sngception and Proprioception
Status:
RECRUITING
Status Verified Date:
2024-10
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:
None
Brief Summary:
Precision medicine is defined as an emerging approach for disease treatment and prevention that takes into account individual variability in genes environment and lifestyle for each person by the Precision Medicine Initiative
Patients have different response to different treatment modalities and sorepain medicine is no exception In our experience low-level laser LLL ultrasound and prolotherapy can reduce sore pain through different genetic pathway Whether the therapeutic effect is controlled by the genetic variants of those sore pain related genes or not is still in debate The aims of this study are 1 To set up next generation sequencing NGS-based approach to find genetic variants which can determine the response of sngpain treatment modalities and the phenotype of idiopathic scoliosis 2 To find possible metabolomics and proteomic markers of sngpain 3 To determine the algorithm of precision medicine for sngpain control via the genetic markers
Investigators will recruit 80 myofascial pain participant and 80 idiopathic scoliosis participant from Department of Physical Medicine and Rehabilitation National Taiwan University Hospital Bei-Hu Branch in 2023 and 2025 The myofascial pain participant participants will receive LLL ultrasound and prolotherapy and the therapeutic effect will be recorded The clinical trial will evaluate the Sng pain VAS and muscle tone of the idiopathic scoliosis participant The blood and urine samples from the first the second and the third visits will be analyzed by next generation sequencing and mass spectrometry to find the possible biomarker in 2024 and 2025 Investigators expect to develop the individualized treatment plan by means of these biomarkers Hopefully the results will be widely applied in the field of sore pain medicine
Patients have different response to different treatment modalities and sorepain medicine is no exception In our experience low-level laser LLL ultrasound and prolotherapy can reduce sore pain through different genetic pathway Whether the therapeutic effect is controlled by the genetic variants of those sore pain related genes or not is still in debate The aims of this study are 1 To set up next generation sequencing NGS-based approach to find genetic variants which can determine the response of sngpain treatment modalities and the phenotype of idiopathic scoliosis 2 To find possible metabolomics and proteomic markers of sngpain 3 To determine the algorithm of precision medicine for sngpain control via the genetic markers
Investigators will recruit 80 myofascial pain participant and 80 idiopathic scoliosis participant from Department of Physical Medicine and Rehabilitation National Taiwan University Hospital Bei-Hu Branch in 2023 and 2025 The myofascial pain participant participants will receive LLL ultrasound and prolotherapy and the therapeutic effect will be recorded The clinical trial will evaluate the Sng pain VAS and muscle tone of the idiopathic scoliosis participant The blood and urine samples from the first the second and the third visits will be analyzed by next generation sequencing and mass spectrometry to find the possible biomarker in 2024 and 2025 Investigators expect to develop the individualized treatment plan by means of these biomarkers Hopefully the results will be widely applied in the field of sore pain medicine
Detailed Description:
Precision medicine is defined as an emerging approach for disease treatment and prevention that takes into account individual variability in genes environment and lifestyle for each person by the Precision Medicine Initiative
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage by the International Association for the Study of Pain IASPTraditionally soreness or sng is also included as one of the pain sensation Recently the investigators defined sngception as acid andor soreness sensation in the somatosensory system and revealed that analgesia in muscle is through substance P and Tac1
According to the clinical outcome some patients responded to physical agents well and some preferred injections The genetic variants of the above-mentioned genes might be the determining factors of differential therapeutic effects However it took about 4-8 weeks for a patient to switch from one treatment option to another one If the investigators can determine the optimal treatment modality by genetic biomarkers the treatment course and total expanse will decrease a lot
The investigators hypothesize that the genetic variants of the proposed genes TRPV1 ASIC1a ASIC3 Tac1 COMT TCL1A POMC RGS4 ASIC2 ASIC4 TRPA1 NK1R G2A GPR4 OGR1 TDAG8 TASK1 TASK2 TASK3 TREK1 P2X2 P2X3 P2X5 TRPV4 KCNK1 NTSR1 NTSR2 CaV32 Nav11 Piezo1 and Piezo2 Runx3 or Egr3 endothelin converting enzyme-like 1 ECEL1 myosin heavy chain genes MYH3 and MYH8 myosin-binding protein C gene MYBPC1 and TNNI2 TNNT3 and TPM2 that encode the muscle regulatory proteins troponin I troponin T and beta-tropomyosin could be the prognostic biomarkers of sngpain treatments or proprioceptive function
1Specific Aims
1 To set up next generation sequencing NGS-based approach to find genetic variants which can determine the response of sngpain treatment modalities and the phenotype of idiopathic scoliosis
2 To find possible metabolomics and proteomic markers of sngpain
3 To determine the algorithm of precision medicine for sngpain control via the genetic markers
2In the past years our team had some achievements to justify the search of genetic variants for development of a new sorepain treatment algorithm
1 Analgesia of LLLT is through TRPV1
2 Analgesia by therapeutic ultrasound is through ASIC3
3 Dextrose injection decreased chronic muscle pain through ASIC1a
4 Biomarker for sngpain in fibromyalgia
3Study design
1 Participants from cohort A-Myofascial pain syndrome The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital
B Clinical trail design
1 After obtaining the informed consent the basic demographic data including age gender job education level and past medical history of eligible participant are collected
2 The eligible participant first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 Jcm2 at trigger point of upper trapezius muscle The pre- and post-treatment VAS-pain and VAS-sng are collected for LLLT phenotype determination respectively
3 Then they are conveniently assigned into two groups 40 subjects in each group A therapeutic ultrasound group B prolotherapy group Group A receives therapeutic ultrasound Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle No other medication or physical modality was given to avoid efficacy interference in both groups
4 The recruited participant receive evaluation before and after injection and 2-week after injection The primary outcome is VAS-pain and VAS-sng The secondary outcomes are pain threshold muscle tone and SF-36 Venous blood and urine samples were collected at first visit and 2-week visit respectively The buffy coat is separated after centrifugation and stored as well The urine samples were aliquoted and stored at -80 ºC in a locked freezer for future analysis
5 Rescue therapy cross-over treatment If the participant does not satisfy with their first round treatment and the improvement of VAS is less than 10 then they are eligible to receive the rescue therapy-the treatment in the other group And they will return to clinic for another 2 weeks The outcome variables will be collected in the 3rd visit as well
2 Participants from cohort B-idiopathic scoliosis The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital and Taichung Veteran Hospital
B Clinical Trail design
1 After obtaining the informed consent the basic demographic data including age gender job education level physical activity level and past medical history of eligible participant are collected
2 The recruited participant receive evaluation for once only The collected parameters include Cobbs angle spine rotational angle VAS-pain and VAS-sng strength and tone of paraspinal muscle and SF-36 Venous blood and urine samples were also collected
Data analyses will be performed as previously described Briefly the raw sequencing data will be aligned to the reference human genome Feb 2009 GRCh37hg19 using BWA-MEM The investigators will use Picard to perform necessary data conversion sorting and indexing The main variant calling process for both single nucleotide variants and indels will be operated with the GATK software package Structural variants will also be identified The investigators will apply ANNOVAR to appropriately annotate the genetic variants this include at least gene annotation amino acid change annotation SIFT scores PolyPhen2 score dbSNP identifiers 1000 Genome Project allele frequencies gnomAD allele frequencies and ClinVar database with variant clinical significance The investigators will then use IGV to view the mapping and annotation of sequences on a graphic interface
The allele frequencies of variants of interest will be compared between different groups of participants The investigators will look for possible rare variants with very strong effects the single-gene model as well as relatively common variants with moderate to strong effects the complex phenotype model
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage by the International Association for the Study of Pain IASPTraditionally soreness or sng is also included as one of the pain sensation Recently the investigators defined sngception as acid andor soreness sensation in the somatosensory system and revealed that analgesia in muscle is through substance P and Tac1
According to the clinical outcome some patients responded to physical agents well and some preferred injections The genetic variants of the above-mentioned genes might be the determining factors of differential therapeutic effects However it took about 4-8 weeks for a patient to switch from one treatment option to another one If the investigators can determine the optimal treatment modality by genetic biomarkers the treatment course and total expanse will decrease a lot
The investigators hypothesize that the genetic variants of the proposed genes TRPV1 ASIC1a ASIC3 Tac1 COMT TCL1A POMC RGS4 ASIC2 ASIC4 TRPA1 NK1R G2A GPR4 OGR1 TDAG8 TASK1 TASK2 TASK3 TREK1 P2X2 P2X3 P2X5 TRPV4 KCNK1 NTSR1 NTSR2 CaV32 Nav11 Piezo1 and Piezo2 Runx3 or Egr3 endothelin converting enzyme-like 1 ECEL1 myosin heavy chain genes MYH3 and MYH8 myosin-binding protein C gene MYBPC1 and TNNI2 TNNT3 and TPM2 that encode the muscle regulatory proteins troponin I troponin T and beta-tropomyosin could be the prognostic biomarkers of sngpain treatments or proprioceptive function
1Specific Aims
1 To set up next generation sequencing NGS-based approach to find genetic variants which can determine the response of sngpain treatment modalities and the phenotype of idiopathic scoliosis
2 To find possible metabolomics and proteomic markers of sngpain
3 To determine the algorithm of precision medicine for sngpain control via the genetic markers
2In the past years our team had some achievements to justify the search of genetic variants for development of a new sorepain treatment algorithm
1 Analgesia of LLLT is through TRPV1
2 Analgesia by therapeutic ultrasound is through ASIC3
3 Dextrose injection decreased chronic muscle pain through ASIC1a
4 Biomarker for sngpain in fibromyalgia
3Study design
1 Participants from cohort A-Myofascial pain syndrome The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital
B Clinical trail design
1 After obtaining the informed consent the basic demographic data including age gender job education level and past medical history of eligible participant are collected
2 The eligible participant first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 Jcm2 at trigger point of upper trapezius muscle The pre- and post-treatment VAS-pain and VAS-sng are collected for LLLT phenotype determination respectively
3 Then they are conveniently assigned into two groups 40 subjects in each group A therapeutic ultrasound group B prolotherapy group Group A receives therapeutic ultrasound Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle No other medication or physical modality was given to avoid efficacy interference in both groups
4 The recruited participant receive evaluation before and after injection and 2-week after injection The primary outcome is VAS-pain and VAS-sng The secondary outcomes are pain threshold muscle tone and SF-36 Venous blood and urine samples were collected at first visit and 2-week visit respectively The buffy coat is separated after centrifugation and stored as well The urine samples were aliquoted and stored at -80 ºC in a locked freezer for future analysis
5 Rescue therapy cross-over treatment If the participant does not satisfy with their first round treatment and the improvement of VAS is less than 10 then they are eligible to receive the rescue therapy-the treatment in the other group And they will return to clinic for another 2 weeks The outcome variables will be collected in the 3rd visit as well
2 Participants from cohort B-idiopathic scoliosis The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital and Taichung Veteran Hospital
B Clinical Trail design
1 After obtaining the informed consent the basic demographic data including age gender job education level physical activity level and past medical history of eligible participant are collected
2 The recruited participant receive evaluation for once only The collected parameters include Cobbs angle spine rotational angle VAS-pain and VAS-sng strength and tone of paraspinal muscle and SF-36 Venous blood and urine samples were also collected
Data analyses will be performed as previously described Briefly the raw sequencing data will be aligned to the reference human genome Feb 2009 GRCh37hg19 using BWA-MEM The investigators will use Picard to perform necessary data conversion sorting and indexing The main variant calling process for both single nucleotide variants and indels will be operated with the GATK software package Structural variants will also be identified The investigators will apply ANNOVAR to appropriately annotate the genetic variants this include at least gene annotation amino acid change annotation SIFT scores PolyPhen2 score dbSNP identifiers 1000 Genome Project allele frequencies gnomAD allele frequencies and ClinVar database with variant clinical significance The investigators will then use IGV to view the mapping and annotation of sequences on a graphic interface
The allele frequencies of variants of interest will be compared between different groups of participants The investigators will look for possible rare variants with very strong effects the single-gene model as well as relatively common variants with moderate to strong effects the complex phenotype model
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