Precision Medicine for Sng/Pain Control (SNG)

November 18, 2025 updated by: National Taiwan University Hospital
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 find genetic SNPs which can determine the response of sore /pain treatment modalities. (2) To find possible metabolomics and proteomic markers of sore /pain. (3) To determine the algorithm of precision medicine for sore /pain control via the genetic markers. Investigators will recruit 80 myofascial pain patients from Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Bei-Hu Branch in 2021 and 2022. The participants will receive LLL, ultrasound, and prolotherapy, and the therapeutic effect will be recorded. 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 2023 and 2024. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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). The musculoskeletal disorders are not only the most common cause of chronic sore/pain, but they also result in significant disability in about 50% of sufferers in the US. Furthermore, since these disorders are the most common cause of severe, long-term pain and disability in the elderly over 65 years. In the practice of pain medicine, the doctors predominantly use multi-modal treatment, including medications, physical agents, and injection, to relieve patients' discomfort.

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.

(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 sore/pain in fibromyalgia.

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 investigators can determine the optimal treatment modality by genetic biomarkers, the treatment course and total expanse will decrease a lot.

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) could be the prognostic biomarkers of sore /pain treatments. Our specific Aims are:

  1. To set up next generation sequencing (NGS)-based approach to find genetic variants which can determine the response of sore/pain treatment modalities.
  2. To find possible metabolomics and proteomic markers of sore/pain.
  3. To determine the algorithm of precision medicine for sore/pain control via the genetic markers.

Six. study design I Patient eligibility Investigators will recruit patients from National Taiwan University Hospital Bei-Hu Branch.

Inclusion criteria: (1) Age between 20-100 years old. (2) Diagnosed as myofascial pain syndrome patients and willing to receive treatment (including LLLT, therapeutic ultrasound, and local dextrose injection therapy). The diagnosis of MPS was confirmed by the Principal Investigator using the criteria of taut band, trigger point, and radiating pain.

Exclusion criteria: Those having active infection, malignancy, and hematological diseases were excluded. The patients had received local injection at upper trapezius within 3 months are also excluded.

II Study design and flow

  1. After obtaining the informed consent, the basic demographic data, including age, gender, job, education level, and past medical history of eligible patients are collected.
  2. 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. The pre- and post-treatment VAS-pain and VAS-sng are collected for LLLT phenotype determination, respectively.
  3. Then, they are randomly assigned into two groups (40 subjects in each group): A. therapeutic ultrasound group; B. prolotherapy group. Group A receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle. Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution. To ensure that the needle was not in a blood vessel, the needle was aspirated before injection. The same physician (the principal investigator) injects all patients to avoid inter-physician variability. No other medication or physical modality was given to avoid efficacy interference in both groups.
  4. The recruited patients receive evaluation before and after injection, and 2-week after injection. The primary outcome is VAS-pain and VAS-sore (visual analogue scale) with a score of 0-100, where 100 is the value representing the highest degree of pain. The secondary outcomes are pain threshold, muscle tone, and SF-36-a questionnaire consists of 36 items and 8 domains addressing the patient's perception of their QoL. Venous blood and urine samples were collected at first visit and 2-week visit, respectively. The blood samples were labeled with an anonymized ID number, centrifuged, and stored at -80 ºC in a locked freezer until the time of future processing. 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 1.0, 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.

(1) DNA extraction and NGS-based sequencing and genotyping Genomic DNA will be extracted from peripheral blood mononuclear cells of the participants using the Gentra Puregene kit following the protocol from the manufacturer, and subjected to agarose gel and O.D. ratio tests to confirm its purity and concentration. DNA will be fragmented using Covaris, aiming at the peak length of 800 bp. Illumina libraries will be generated from gDNA using TruSeq Library Preparation Kit.

DNA capture probes will be custom-designed to target 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 and will be synthesized using the Roche KAPA HyperChoice protocol. All the coding regions and non-coding regions (promoters, introns, 5' and 3' untranslated regions) of these 8 genes will be included.

NGS target region enrichment will be applied to enrich/capture the target region (~148 Kb). The enriched libraries will then be sequenced using Illumina MiSeq to generate paired-end reads of 300 bp. The expected depth of the targeted regions will be 200x on average.

(2) Metabolomic and proteomic analysis

  1. Briefly, The LC-MS analyses of urine and serum involved using an Agilent 1290 UPLC system (ACQUITY UPLC HSS T3 column, 2.1×100 mm; 1.8 µm; Waters, Milford, MA, USA) coupled with the 6540-Quadrupole-Time-of-Flight (QTOF) mass system (Agilent Technologies, Santa Clara, CA, USA). MS raw files were converted to the mzXML format using Trapper (ISB) and processed by TIPick, an in-house package. After TIPick processing, the scaling-based normalization was performed according to the total ion abundances from each UHPLC-MS data set.
  2. The LC-MS lipidomic profiling was performed and described in detail. Concisely, lipidomic profiling was run on a ZORBAX Eclipse Plus C18 (2.1 x 100 mm, 1.8 µm, Agilent Technologies, Waldbronn, Germany) for QTOF, as well as mobile phase A consisted of 0.1% aqueous formic acid and 10 mM ammonium acetate and mobile phase B consisted of 0.1% formic acid and 10 mM ammonium acetate in ACN/isopropyl alcohol (50/50). The autosampler and column oven were maintained at 4°C and 55°C, respectively. The injection volume was 5 μl. MS acquisition was executed in the precursor ion scan (PIS) mode and multiple reaction monitoring (MRM) mode.
  3. All UPLC-MS raw data were converted to mzXML format by using Trapper (ISB) and normalized by TIPick, an in-house package, as well as peak enhancement and peak chosen for the targeted metabolites. An in-house database of sphingomyelins (SM), lysophosphatidylcholine (LysoPC), ceramides (Cer), phosphatidylcholines (PCs), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and cerebroside (CB) in the Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, was used for screening.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
    • Taiwan
      • Taipei, Taiwan, Taiwan, 802
        • National Taiwan University Hospital Bei-Hu Branch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • (1) Age between 20-100 years old.
  • (2) Diagnosed as myofascial pain syndrome patients and willing to receive treatment (including LLLT, therapeutic ultrasound, and local dextrose injection therapy).

Exclusion Criteria:

  • Those having active infection, malignancy, and hematological diseases were excluded. The patients had received local injection at upper trapezius within 3 months are also excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: A.therapeutic ultrasound group
Group A receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle.
Device: LASER
The eligible participants 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.
Device: A.therapeutic ultrasound group
Group A receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle.
Other Names:
  • Group A
Drug: B.prolotherapy group
Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution.
Other Names:
  • Group B
Active Comparator: B.prolotherapy group
Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution.
Device: LASER
The eligible participants 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.
Device: A.therapeutic ultrasound group
Group A receives 1 MHz therapeutic ultrasound for 5 min at a frequency of 2-3 times per week at the painful upper trapezius muscle.
Other Names:
  • Group A
Drug: B.prolotherapy group
Group B receives hypertonic prolotherapy at perimysium of upper trapezius muscle. The injectant is 5ml 5% dextrose solution.
Other Names:
  • Group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual Analogue Scale (VAS) - first
Time Frame: Baseline Visual Analogue Scale
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-10. score 0 means 'no pain' and score 10 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(1-4 point), moderate pain (5-7 point ), and severe pain (8-10 point).
Baseline Visual Analogue Scale
Visual Analogue Scale (VAS) - second
Time Frame: Change from Baseline Visual Analogue Scale at 2 weeks.
Visual Analogue Scale (VAS) anchor the patient's mark, providing a range of scores from 0-10. score 0 means 'no pain' and score 10 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(1-4 point), moderate pain (5-7 point ), and severe pain (8-10 point).
Change from Baseline Visual Analogue Scale at 2 weeks.
Visual Analogue Scale (VAS) - third
Time Frame: 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 0-10. score 0 means 'no pain' and score 10 means 'pain worst'. VAS have been recommended: no pain (0 point), mild pain(1-4 point), moderate pain (5-7 point ), and severe pain (8-10 point).
Change from Baseline Visual Analogue Scale at 4 weeks (if crossover).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SF-36
Time Frame: Baseline, week 2, week 4 (if crossover)
Quality of life (36-Item Short Form Survey)
Baseline, week 2, week 4 (if crossover)
Pain thresholds
Time Frame: Baseline, week 2, week 4 (if crossover)
Pain thresholds range from 0 to 800. Low thresholds means higher pain sensitivity (Pain tolerance) or muscle inflammation.
Baseline, week 2, week 4 (if crossover)
Myoton-Muscle tone
Time Frame: Baseline, week 2, week 4 (if crossover)
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.
Baseline, week 2, week 4 (if crossover)
Myoton- Dynamic stiffness
Time Frame: Baseline, week 2, week 4 (if crossover)
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.
Baseline, week 2, week 4 (if crossover)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Collaborators

Ministry of Science and Technology, Taiwan
National Health Research Institutes, Taiwan

Investigators

  • Study Director: Der-Sheng Han, Physician, International Committee of Medical Journal Editors

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 28, 2021

Primary Completion (Actual)

October 31, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

October 12, 2021

First Submitted That Met QC Criteria

November 29, 2021

First Posted (Actual)

December 13, 2021

Study Record Updates

Last Update Posted (Actual)

November 21, 2025

Last Update Submitted That Met QC Criteria

November 18, 2025

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202011007RIND

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The data doesn't shared with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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