The Causal Connection Between Sng and Muscle Acidosis

NCT04049253 | Unknown

• 1 other identifier: N201902030
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This proposed study suggests that peripheral tissue acidosis sensed by the somatosensory system (sngceptin) would evoke the sng perception in the brain. This hypothesis is based on investigators preliminary data that the peripheral muscle acidosis will evoked the central sng perception. This proposed study also identify the detection of brain activation areas related to the peripheral muscle acidosis. Investigators will know specific brain areas related to sng perception evoked by the peripheral muscle acidosis and, accordingly, a novel mechanism and potential treatment for sng would be developed in this proposed study.

Conditions

Muscle Acidosis

Keywords

sngceptin; soreness; muscle acidosis

Outcome Measures

Primary Outcomes (1)

• Brain functional magnetic resonance imaging

  All images will be acquired on a 3 Tesla MRI system (MAGNETOM Prisma, Siemens, Erlangen, Germany) with a 20-channel head coil. To obtain an anatomical reference, high-resolution T1-weighted imaging was performed using a 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence: repetition time (TR)/echo time (TE) = 2000 ms/3 ms, flip angle = 9°, field of view (FOV) = 256 × 192 × 208 mm3, acquisition matrix = 256 × 192 × 208, resulting in isotropic spatial resolution of 1 mm3. The task fMRI will be performed using an echo planar imaging (EPI) sequence with a twice-refocused balanced echo. The imaging parameters are: TR/TE = 2000/20 ms, slice thickness = 3.5 mm, 80 × 80 acquisition matrix, FOV = 200 × 200 mm, and in-plane spatial resolution = 3.0 mm x 3.0 mm.

  The whole procedures will be done within 50 minutes. Before the injection, the subject will receive anatomical MRI scan (10 minutes) and baseline fMRI scan (10 minutes) After that, the acid or pH 7.4 PBS will be given into the midpoint of the left tibial

Secondary Outcomes (2)

• The visual analog scale (VAS) of "sng" in the legs

  Through fMRI completion an average of 6 months

• Muscle pressure pain threshold

  Through fMRI completion an average of 1 week

Other Outcomes (5)

• 36-Item Short Form Health Survey (RAND)

  Up to 6 months before signing the informed consent form

• The visual analog scale (VAS) of "sng" in the back

  Through fMRI completion an average of 6 months

• Oswestry disability index

  Up to 6 months before signing the informed consent form

Study Arms (2)

Acidic phosphate buffer solution

EXPERIMENTAL

pH5.2 phosphate buffer solution

Drug: Phosphate Buffer Solution

Neutral phosphate buffer solution

PLACEBO COMPARATOR

pH7.4 phosphate buffer solution

Drug: Phosphate Buffer Solution

Interventions

Phosphate Buffer Solution DRUG

Phosphate-buffered saline (abbreviated PBS) is a buffer solution commonly used in biological research. It is a water-based salt solution containing disodium hydrogen phosphate, sodium dihydrogen phosphate. The buffer helps to maintain a constant pH. The osmolarity and ion concentrations of the solutions match those of the human body (isotonic).

Also known as: Sodium phosphate solution, Phosphate buffered saline

Acidic phosphate buffer solution; Neutral phosphate buffer solution

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject ages ranges from 20-45 years old.
• The subject has no chronic pain symptoms or complaint in last 6 months.
• The subject is subjectively able to discriminate sng and pain.
• The subject has no history of major diseases that required treatment or currently being under treatment.
• Gender: men and women half
• The used hand of subject is the right hand.
• The educational level of subject is more than 9 years (graduated from junior high school)
• The subject didn't have physical and mental illness
• The subject didn't take prescribed medicine.
• The VAS questionnaire must be 0 point both of low back "pain" and low back "soreness" assessment.
• The subject who can fill the informed consent after understanding the purpose and medical help of this trial.

You may not qualify if:

• The subject is unable to reliably delineate or assess his or her own pain by anatomical location/distribution (e.g., the subject cannot reliably tell the difference between his or her back pain and lower limb pain and cannot rate the intensity of each separately).
• The subject has undergone lumbar spine surgery within the last 6 months or has received treatment with epidural injections, nerve blocks, or acupuncture for lower skin electrical resistance within 4 weeks before screening.
• The subject had a malignancy according to his/her report.
• The subject had allergic to lidocaine or monobasic sodium phosphate and dibasic sodium phosphate
• The subject has had a positive test for HIV antibody or a history of HIV according to his/her report.
• The subject has had a positive test for hepatitis B surface antigen or hepatitis C antibody according to his/her report.
• The subject has a history of alcohol or narcotic substance abuse according to his/her report.
• The subject is female and is pregnant or breastfeeding at the time of the screening visit or plans to become pregnant during the study period.
• The subject cannot perform brain MRI scanning who had metal implants of head (such as fixed dentures, metal bone plate, vascular clamp, vascular embolization treatment coil, deep brain stimulator, artificial electronic ear, etc.), implants of head which affecting the image quality (such as the ventricle peritoneal catheter, etc.), implantation of permanent heart rate regulator, etc.
• The subject has suffered from claustrophobia.
• The subject has a history of spinal surgery.
• The VAS questionnaire not be 0 point either low back "pain" or low back "soreness" assessment.
• The subject has mental comorbidity (such as depression, panic disorder, etc)
• The subject has suffered from brain disease and had brain surgery.
• The subject has taken prescribed medicine which can affect specific function of brian (such as sleeping pills, tranquilizer, etc.).

Sponsors & Collaborators

• Taipei Medical University Hospital: lead

Study Sites (1)

Taipei Medical University Hospital

Taipei, No.252, Wusing St., Sinyi Dist., 11031, Taiwan

RECRUITING

Related Publications (6)

• Issberner U, Reeh PW, Steen KH. Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? Neurosci Lett. 1996 Apr 26;208(3):191-4. doi: 10.1016/0304-3940(96)12576-3.

  PMID: 8733302 BACKGROUND

• Law LAF, Sluka KA, McMullen T, Lee J, Arendt-Nielsen L, Graven-Nielsen T. Acidic buffer induced muscle pain evokes referred pain and mechanical hyperalgesia in humans. Pain. 2008 Nov 30;140(2):254-264. doi: 10.1016/j.pain.2008.08.014. Epub 2008 Oct 2.

  PMID: 18835099 BACKGROUND

• Lin 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.

  PMID: 30486810 BACKGROUND

• Fujii Y, Ozaki N, Taguchi T, Mizumura K, Furukawa K, Sugiura Y. TRP channels and ASICs mediate mechanical hyperalgesia in models of inflammatory muscle pain and delayed onset muscle soreness. Pain. 2008 Nov 30;140(2):292-304. doi: 10.1016/j.pain.2008.08.013. Epub 2008 Oct 1.

  PMID: 18834667 BACKGROUND

• Chen CC, Wong CW. Neurosensory mechanotransduction through acid-sensing ion channels. J Cell Mol Med. 2013 Mar;17(3):337-49. doi: 10.1111/jcmm.12025. Epub 2013 Mar 14.

  PMID: 23490035 BACKGROUND

• Chen WN, Lee CH, Lin SH, Wong CW, Sun WH, Wood JN, Chen CC. Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia. Mol Pain. 2014 Jun 23;10:40. doi: 10.1186/1744-8069-10-40.

  PMID: 24957987 BACKGROUND

Study Officials

• Jiann-Her Lin, MD/PhD

  Taipei Medical University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiann-Her Lin, MD/PhD

CONTACT

+886973405133; jiannher@me.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: August 8, 2019
• Study Start: July 11, 2019
• Primary Completion: July 31, 2021
• Study Completion: January 1, 2023
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

TW (1)