RehabilitationNCT06161038
Precision Medicine for Nociception, Sngception and Proprioception.
A study testing LASER, Ultrasound and Prolotherapy in people with Rehabilitation and Pain, Shoulder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 100 years
- Conditions the study is for
- Rehabilitation, Pain, Shoulder, Pain, Chronic
- What is being tested?
- LASER, Ultrasound and Prolotherapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Oct 2023to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1.Cohort A:
- Age between 20-100 years old. (2) VAS>=30 or VAS>=30 at 4 kg pressure (3) Diagnosed as myofascial pain syndrome patients and willing to receive treatment (including LLLT, therapeutic ultrasound, and local dextrose injection therapy) 2. Cohort B:
- Age between 13-65 years old.
- Diagnosed as idiopathic scoliosis The diagnosis of scoliosis was confirmed by antero-posterior plain Xray with Cobbs angle larger than 10 degrees.
Who cannot join
- 1.Cohort A: Those having active infection, malignancy, and hematological diseases were excluded. The patients had received local injection at upper trapezius within 6 months are also excluded.
- 2.Cohort B:
- Those having active infection, malignancy, and hematological diseases were excluded.
- Those having specific etiologies of scoliosis, including congenital scoliosis due to malformation or faulty segmentation of the vertebrae and neuromuscular scoliosis due to muscular imbalance, syndromic scoliosis or degenerative scoliosis.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
National Taiwan University Hospital Bei-Hu Branch
Taipei, Taiwan, 802
About this study
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 sore/pain 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 sng/pain treatment modalities and the phenotype of idiopathic scoliosis. (2) To find possible metabolomics and proteomic markers of sng/pain. (3) To determine the algorithm of precision medicine for sng/pain 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.
Read the 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 (IASP).Traditionally, soreness, or sng, is also included as one of the pain sensation. Recently, the investigators defined sngception as acid and/or 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, CaV3.2, Nav1.1, 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 sng/pain treatments or proprioceptive function.
1.Specific Aims
- To set up next generation sequencing (NGS)-based approach to find genetic variants which can determine the response of sng/pain treatment modalities and the phenotype of idiopathic scoliosis.
- To find possible metabolomics and proteomic markers of sng/pain.
- To determine the algorithm of precision medicine for sng/pain control via the genetic markers.
2.In the past years, our team had some achievements to justify the search of genetic variants for development of a new sore/pain treatment algorithm.
- Analgesia of LLLT is through TRPV1.
- Analgesia by therapeutic ultrasound is through ASIC3.
- Dextrose injection decreased chronic muscle pain through ASIC1a.
- Biomarker for sng/pain in fibromyalgia.
3.Study design
(1) Participants from cohort A-Myofascial pain syndrome: The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital.
- Clinical trail design:
- After obtaining the informed consent, the basic demographic data, including age, gender, job, education level, and past medical history of eligible participant are collected.
- The eligible participant first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle. The pre- and post-treatment VAS-pain and VAS-sng are collected for LLLT phenotype determination, respectively.
- 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.
- 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.
- 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.
- Clinical Trail design:
- 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.
- The recruited participant receive evaluation for once only. The collected parameters include Cobb's 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, GRCh37/hg19) 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).
- Conditions
- Rehabilitation, Pain, Shoulder, Pain, Chronic, Idiopathic Scoliosis
- Being tested
- LASER, Ultrasound, Prolotherapy
- Keywords
- Sng / Pain, Precision medicine, Next generation sequencing, Proprioception, Prolotherapy
- Medical subject headings
- Shoulder Pain, Chronic Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LASERDevice
LLLT with a 685-nm wavelength and an output of 30 mW (BTL-5000 Laser, BTL, Stevenage, UK) at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle.
UltrasoundDevice
Also called Therapeutic ultrasound
1 MHz therapeutic ultrasound for 5 min at a frequency of 4-6 times two week at the painful upper trapezius muscle.
ProlotherapyDrug
Also called Hypertonic prolotherapy
Hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A-A.therapeutic ultrasound group | Active comparator | 1. Participants: Age between 20-100 years old who diagnosed as myofascial pain syndrome patients and willing to receive treatment.
2. Intervention: Group A (A) receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle. Receives: Device: LASER; Device: Ultrasound; Drug: Prolotherapy |
| Cohort A-B.prolotherapy group | Active comparator | 1. Participants: Age between 20-100 years old who diagnosed as myofascial pain syndrome patients and willing to receive treatment.
2. Intervention: Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution. Receives: Device: LASER; Device: Ultrasound; Drug: Prolotherapy |
| Cohort B | No intervention | 1. Participants: Age between 13-65 years old who diagnosed as idiopathic scoliosis The diagnosis of scoliosis was confirmed by antero-posterior plain Xray with Cobbs angle larger than 10 degrees. 2. Intervention: None |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analogue Scale (VAS)
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
Measured: Baseline Visual Analogue Scale.
Visual Analogue Scale (VAS)
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
Measured: Only cohort A: Change from Baseline Visual Analogue Scale at 2 weeks.
Visual Analogue Scale (VAS)
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
Measured: Only cohort A: Change from Baseline Visual Analogue Scale at 4 weeks (if crossover)
Secondary outcomes (4)
Myoton-Muscle tone
Muscle tone means state of muscle tension, which unit is Natural oscillation frequency [Hz]. This higher or lower value meaning is uncertainty. The range was from 10 to 30 Hz.
Measured: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Myoton- Dynamic stiffness
Muscle tone means muscle biomechanical properties, which unit is N/m. This higher or lower value meaning is uncertainty. The range was from 100 to 600 Hz.
Measured: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Pain thresholds
The item evaluate by SBMEDIC Algometer. The investigators used a device to press the participant's upper trapezius muscle until the subject call "uncomfortable" and then recorded the value. The investigators catch mean by three times.
Pain thresholds range from 0 to 800 Kpa. Low thresholds means higher pain sensitivity (Pain tolerance) or muscle inflammation.
Measured: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
SF-36
Quality of life (36-Item Short Form Survey)
Measured: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start1 Oct 2023
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for RehabilitationStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 1. Cohort A-Myofascial pain syndrome The eligible patients first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle. Then, they are conveniently assigned into two groups (40 subjects in each group): A. therapeutic ultrasound group; B. prolotherapy group. The same physician (the principal investigator) injects all patients to avoid inter-physician variability. 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. 2. Cohort B-idiopathic scoliosis: The recruited patients receive evaluation for once only. The collected parameters include Cobb's angle, spine rotational angle, VAS-pain and VAS-sng (visual analogue scale), pain threshold, strength and tone of paraspinal muscle, and SF-36.
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Science and Technology Council, National Health Research Institutes, Taiwan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06161038
- Sponsor's protocol ID
- 202302118RINA
- Status last verified
- Aug 2026
- First submitted
- 5 Dec 2023
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data doesn't shared with other researchers.
Publications
Assaraf E, Blecher R, Heinemann-Yerushalmi L, Krief S, Carmel Vinestock R, Biton IE, Brumfeld V, Rotkopf R, Avisar E, Agar G, Zelzer E. Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity. Nat Commun. 2020 Jun 23;11(1):3168. doi: 10.1038/s41467-020-16971-6.
PubMed 32576830Avrampou K, Pryce KD, Ramakrishnan A, Sakloth F, Gaspari S, Serafini RA, Mitsi V, Polizu C, Swartz C, Ligas B, Richards A, Shen L, Carr FB, Zachariou V. RGS4 Maintains Chronic Pain Symptoms in Rodent Models. J Neurosci. 2019 Oct 16;39(42):8291-8304. doi: 10.1523/JNEUROSCI.3154-18.2019. Epub 2019 Jul 15.
PubMed 31308097Chang KV, Wu WT, Han DS, Ozcakar L. Static and Dynamic Shoulder Imaging to Predict Initial Effectiveness and Recurrence After Ultrasound-Guided Subacromial Corticosteroid Injections. Arch Phys Med Rehabil. 2017 Oct;98(10):1984-1994. doi: 10.1016/j.apmr.2017.01.022. Epub 2017 Feb 27.
PubMed 28245972Cho CH, Lho YM, Ha E, Hwang I, Song KS, Min BW, Bae KC, Kim DH. Up-regulation of acid-sensing ion channels in the capsule of the joint in frozen shoulder. Bone Joint J. 2015 Jun;97-B(6):824-9. doi: 10.1302/0301-620X.97B6.35254.
PubMed 26033064Choi JH, Yarishkin O, Kim E, Bae Y, Kim A, Kim SC, Ryoo K, Cho CH, Hwang EM, Park JY. TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells. Exp Mol Med. 2018 Nov 12;50(11):1-13. doi: 10.1038/s12276-018-0172-4.
PubMed 30416196Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015 Feb 26;372(9):793-5. doi: 10.1056/NEJMp1500523. Epub 2015 Jan 30.
PubMed 25635347Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4667-72. doi: 10.1073/pnas.1221400110. Epub 2013 Mar 4.
PubMed 23487782Genovese TJ, Mao JJ. Genetic Predictors of Response to Acupuncture for Aromatase Inhibitor-Associated Arthralgia Among Breast Cancer Survivors. Pain Med. 2019 Jan 1;20(1):191-194. doi: 10.1093/pm/pny067.
PubMed 29912452Hsiung YC, Lin PC, Chen CS, Tung YC, Yang WS, Chen PL, Su TC. Identification of a novel LDLR disease-causing variant using capture-based next-generation sequencing screening of familial hypercholesterolemia patients in Taiwan. Atherosclerosis. 2018 Oct;277:440-447. doi: 10.1016/j.atherosclerosis.2018.08.022.
PubMed 30270083Li L, Wang HM, Shen Y. Chinese SF-36 Health Survey: translation, cultural adaptation, validation, and normalisation. J Epidemiol Community Health. 2003 Apr;57(4):259-63. doi: 10.1136/jech.57.4.259.
PubMed 12646540Liao HW, Kuo CH, Chao HC, Chen GY. Post-column infused internal standard assisted lipidomics profiling strategy and its application on phosphatidylcholine research. J Pharm Biomed Anal. 2020 Jan 30;178:112956. doi: 10.1016/j.jpba.2019.112956. Epub 2019 Oct 30.
PubMed 31704131Lin JH, Hung CH, Han DS, Chen ST, Lee CH, Sun WZ, Chen CC. Sensing acidosis: nociception or sngception? J Biomed Sci. 2018 Nov 29;25(1):85. doi: 10.1186/s12929-018-0486-5.
PubMed 30486810Lin YH, Wu CC, Lin YH, Lu YC, Chen CS, Liu TC, Chen PL, Hsu CJ. Targeted Next-Generation Sequencing Facilitates Genetic Diagnosis and Provides Novel Pathogenetic Insights into Deafness with Enlarged Vestibular Aqueduct. J Mol Diagn. 2019 Jan;21(1):138-148. doi: 10.1016/j.jmoldx.2018.08.007. Epub 2018 Sep 28.
PubMed 30268946Masingue M, Faure J, Sole G, Stojkovic T, Leonard-Louis S. A novel nonsense PIEZO2 mutation in a family with scoliosis and proprioceptive defect. Neuromuscul Disord. 2019 Jan;29(1):75-79. doi: 10.1016/j.nmd.2018.10.005. Epub 2018 Nov 8.
PubMed 30578100Niculescu AB, Le-Niculescu H, Levey DF, Roseberry K, Soe KC, Rogers J, Khan F, Jones T, Judd S, McCormick MA, Wessel AR, Williams A, Kurian SM, White FA. Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs. Mol Psychiatry. 2019 Apr;24(4):501-522. doi: 10.1038/s41380-018-0345-5. Epub 2019 Feb 12.
PubMed 30755720
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Medicine for Nociception, Sngception and Proprioception.
- ClinicalTrials.gov ID
- NCT06161038
- Acronym / sponsor ID
- 202302118RINA
- Conditions
- Rehabilitation, Pain, Shoulder, Pain, Chronic, Idiopathic Scoliosis
- Keywords
- Sng / Pain, Precision medicine, Next generation sequencing, Proprioception, Prolotherapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- National Science and Technology Council, National Health Research Institutes, Taiwan
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 7 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 sore/pain 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 sng/pain treatment modalities and the phenotype of idiopathic scoliosis. (2) To find possible metabolomics and proteomic markers of sng/pain. (3) To determine the algorithm of precision medicine for sng/pain 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 (IASP).Traditionally, soreness, or sng, is also included as one of the pain sensation. Recently, the investigators defined sngception as acid and/or 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, CaV3.2, Nav1.1, 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 sng/pain treatments or proprioceptive function.
1.Specific Aims
- To set up next generation sequencing (NGS)-based approach to find genetic variants which can determine the response of sng/pain treatment modalities and the phenotype of idiopathic scoliosis.
- To find possible metabolomics and proteomic markers of sng/pain.
- To determine the algorithm of precision medicine for sng/pain control via the genetic markers.
2.In the past years, our team had some achievements to justify the search of genetic variants for development of a new sore/pain treatment algorithm.
- Analgesia of LLLT is through TRPV1.
- Analgesia by therapeutic ultrasound is through ASIC3.
- Dextrose injection decreased chronic muscle pain through ASIC1a.
- Biomarker for sng/pain in fibromyalgia.
3.Study design
(1) Participants from cohort A-Myofascial pain syndrome: The investigators will recruit 80 participant from National Taiwan University Hospital and its Branch hospital.
- Clinical trail design:
- After obtaining the informed consent, the basic demographic data, including age, gender, job, education level, and past medical history of eligible participant are collected.
- The eligible participant first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle. The pre- and post-treatment VAS-pain and VAS-sng are collected for LLLT phenotype determination, respectively.
- 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.
- 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.
- 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.
- Clinical Trail design:
- 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.
- The recruited participant receive evaluation for once only. The collected parameters include Cobb's 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, GRCh37/hg19) 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 1. Cohort A-Myofascial pain syndrome The eligible patients first received LLLT with a 685-nm wavelength and an output of 30 mW at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle. Then, they are conveniently assigned into two groups (40 subjects in each group): A. therapeutic ultrasound group; B. prolotherapy group. The same physician (the principal investigator) injects all patients to avoid inter-physician variability. 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. 2. Cohort B-idiopathic scoliosis: The recruited patients receive evaluation for once only. The collected parameters include Cobb's angle, spine rotational angle, VAS-pain and VAS-sng (visual analogue scale), pain threshold, strength and tone of paraspinal muscle, and SF-36.
| Arm | Type | Receives |
|---|---|---|
| Cohort A-A.therapeutic ultrasound group | Active comparator | Device: LASER, Device: Ultrasound, Drug: Prolotherapy1. Participants: Age between 20-100 years old who diagnosed as myofascial pain syndrome patients and willing to receive treatment. 2. Intervention: Group A (A) receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle. |
| Cohort A-B.prolotherapy group | Active comparator | Device: LASER, Device: Ultrasound, Drug: Prolotherapy1. Participants: Age between 20-100 years old who diagnosed as myofascial pain syndrome patients and willing to receive treatment. 2. Intervention: Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution. |
| Cohort B | No intervention | –1. Participants: Age between 13-65 years old who diagnosed as idiopathic scoliosis The diagnosis of scoliosis was confirmed by antero-posterior plain Xray with Cobbs angle larger than 10 degrees. 2. Intervention: None |
Who may qualify
- Ages
- 13 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 20-100 years old. (2) VAS>=30 or VAS>=30 at 4 kg pressure (3) Diagnosed as myofascial pain syndrome patients and willing to receive treatment (including LLLT, therapeutic ultrasound, and local dextrose injection therapy) 2. Cohort B:
- Age between 13-65 years old.
- Diagnosed as idiopathic scoliosis The diagnosis of scoliosis was confirmed by antero-posterior plain Xray with Cobbs angle larger than 10 degrees.
Key exclusion criteria (5 listed)
- 1.Cohort A: Those having active infection, malignancy, and hematological diseases were excluded. The patients had received local injection at upper trapezius within 6 months are also excluded.
- Those having active infection, malignancy, and hematological diseases were excluded.
- Those having specific etiologies of scoliosis, including congenital scoliosis due to malformation or faulty segmentation of the vertebrae and neuromuscular scoliosis due to muscular imbalance, syndromic scoliosis or degenerative scoliosis.
- Pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LASERLLLT with a 685-nm wavelength and an output of 30 mW (BTL-5000 Laser, BTL, Stevenage, UK) at energy densities of 8 J/cm2 at trigger point of upper trapezius muscle. | Device | Cohort A-A.therapeutic ultrasound group, Cohort A-B.prolotherapy group |
| UltrasoundAlso: Therapeutic ultrasound1 MHz therapeutic ultrasound for 5 min at a frequency of 4-6 times two week at the painful upper trapezius muscle. | Device | Cohort A-A.therapeutic ultrasound group, Cohort A-B.prolotherapy group |
| ProlotherapyAlso: Hypertonic prolotherapyHypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution. | Drug | Cohort A-A.therapeutic ultrasound group, Cohort A-B.prolotherapy group |
Primary outcome
Visual Analogue Scale (VAS)
Time frame: Baseline Visual Analogue Scale.
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
Visual Analogue Scale (VAS)
Time frame: Only cohort A: Change from Baseline Visual Analogue Scale at 2 weeks.
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
Visual Analogue Scale (VAS)
Time frame: Only cohort A: Change from Baseline Visual Analogue Scale at 4 weeks (if crossover)
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-100. score 0 means 'no pain' and score 100 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(10-40 point), moderate pain (50-70 point ), and severe pain (80-100 point).
4 secondary outcomes
Myoton-Muscle tone
Time frame: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Myoton- Dynamic stiffness
Time frame: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Pain thresholds
Time frame: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
SF-36
Time frame: Cohort A: Baseline, week 2, week 4 (if crossover); Cohort B: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Background: PubMed 32576830Assaraf E, Blecher R, Heinemann-Yerushalmi L, Krief S, Carmel Vinestock R, Biton IE, Brumfeld V, Rotkopf R, Avisar E, Agar G, Zelzer E. Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity. Nat Commun. 2020 Jun 23;11(1):3168. doi: 10.1038/s41467-020-16971-6.
- Background: PubMed 31308097Avrampou K, Pryce KD, Ramakrishnan A, Sakloth F, Gaspari S, Serafini RA, Mitsi V, Polizu C, Swartz C, Ligas B, Richards A, Shen L, Carr FB, Zachariou V. RGS4 Maintains Chronic Pain Symptoms in Rodent Models. J Neurosci. 2019 Oct 16;39(42):8291-8304. doi: 10.1523/JNEUROSCI.3154-18.2019. Epub 2019 Jul 15.
- Background: PubMed 28245972Chang KV, Wu WT, Han DS, Ozcakar L. Static and Dynamic Shoulder Imaging to Predict Initial Effectiveness and Recurrence After Ultrasound-Guided Subacromial Corticosteroid Injections. Arch Phys Med Rehabil. 2017 Oct;98(10):1984-1994. doi: 10.1016/j.apmr.2017.01.022. Epub 2017 Feb 27.
- Background: PubMed 26033064Cho CH, Lho YM, Ha E, Hwang I, Song KS, Min BW, Bae KC, Kim DH. Up-regulation of acid-sensing ion channels in the capsule of the joint in frozen shoulder. Bone Joint J. 2015 Jun;97-B(6):824-9. doi: 10.1302/0301-620X.97B6.35254.
- Background: PubMed 30416196Choi JH, Yarishkin O, Kim E, Bae Y, Kim A, Kim SC, Ryoo K, Cho CH, Hwang EM, Park JY. TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells. Exp Mol Med. 2018 Nov 12;50(11):1-13. doi: 10.1038/s12276-018-0172-4.
- Background: PubMed 25635347Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015 Feb 26;372(9):793-5. doi: 10.1056/NEJMp1500523. Epub 2015 Jan 30.
- Background: PubMed 23487782Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4667-72. doi: 10.1073/pnas.1221400110. Epub 2013 Mar 4.
- Background: PubMed 29912452Genovese TJ, Mao JJ. Genetic Predictors of Response to Acupuncture for Aromatase Inhibitor-Associated Arthralgia Among Breast Cancer Survivors. Pain Med. 2019 Jan 1;20(1):191-194. doi: 10.1093/pm/pny067.
- Background: PubMed 30270083Hsiung YC, Lin PC, Chen CS, Tung YC, Yang WS, Chen PL, Su TC. Identification of a novel LDLR disease-causing variant using capture-based next-generation sequencing screening of familial hypercholesterolemia patients in Taiwan. Atherosclerosis. 2018 Oct;277:440-447. doi: 10.1016/j.atherosclerosis.2018.08.022.
- Background: PubMed 12646540Li L, Wang HM, Shen Y. Chinese SF-36 Health Survey: translation, cultural adaptation, validation, and normalisation. J Epidemiol Community Health. 2003 Apr;57(4):259-63. doi: 10.1136/jech.57.4.259.
- Background: PubMed 31704131Liao HW, Kuo CH, Chao HC, Chen GY. Post-column infused internal standard assisted lipidomics profiling strategy and its application on phosphatidylcholine research. J Pharm Biomed Anal. 2020 Jan 30;178:112956. doi: 10.1016/j.jpba.2019.112956. Epub 2019 Oct 30.
- Background: PubMed 30486810Lin JH, Hung CH, Han DS, Chen ST, Lee CH, Sun WZ, Chen CC. Sensing acidosis: nociception or sngception? J Biomed Sci. 2018 Nov 29;25(1):85. doi: 10.1186/s12929-018-0486-5.
- Individual participant dataSharing planned: No. The data doesn't shared with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LASER, Ultrasound and Prolotherapy in people with Rehabilitation and Pain, Shoulder, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Analogue Scale (VAS) (time frame: Baseline Visual Analogue Scale.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06161038, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.