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Effect of Flow Rate and pH on Muscle Acidosis

Primary Purpose

Muscle Acidosis

Status

Recruiting

Phase

Not Applicable

Locations

Taiwan

Study Type

Interventional

Intervention

Phosphate Buffer Solution

About this trial

This is an interventional basic science trial for Muscle Acidosis focused on measuring sngception, soreness, muscle acidosis, flow rate

Eligibility Criteria

20 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

The subject has:Neuropathic pain due to causes other than that specified in the inclusion criteria (e.g., post-herpetic neuralgia; painful diabetic neuropathy; mononeuritis multiplex; central poststroke pain; failed back surgery in relation to the presenting episode of radiculopathy; spinal abscess, infection, hematoma, or malignancy; phantom limb pain; peripheral neuropathy due to alcoholism, malignancy, human immunodeficiency virus [HIV], syphilis; drug abuse; vitamin B12 deficiency; hypothyroidism; liver disease; toxic exposure).
Pain that is associated with a substantial somatic pain component (e.g., non-neuropathic/musculoskeletal pain in lower limbs or other parts of the body apart from the back) or more than one cause or potential cause for pain symptoms.Any painful concurrent rheumatic disease such as, but not limited to, fibromyalgia, rheumatoid arthritis, or significant osteoarthritis.
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 LSR within 4 weeks before screening.
The subject had a malignancy according to his/her report.
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 a history of spinal surgery.
The VAS questionnaire not be 0 point either low back "pain" or low back "soreness" assessment.
The subject has suffered from claustrophobia.
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.).
The subject has mental comorbidity (such as depression, panic disorder, etc)
The subject has mental retardation.
The educational level of subject is less than 9 years.
The subject ,who is unable to understand the purpose of this trial and fill the informed consent.

Sites / Locations

Taipei Medical University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Acidic phosphate buffer solution

Neutral phosphate buffer solution

Arm Description

pH5.2 phosphate buffer solution

pH7.4 phosphate buffer solution

Outcomes

Primary Outcome Measures

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

The subject will be asked for sng VAS before infusion and immediately after infusion. Scale range 0 to 10 (1)0: No Sng (2)1-3: Mild Sng (3)4-6: Moderate Sng (4)7-9: Severe Sng (5)10: Worst Sng imaginable

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

The subject will be asked for pain VAS before infusion and immediately after infusion. Scale range 0 to 10 (1)0: No Pain (2)1-3: Mild Pain (3)4-6: Moderate Pain (4)7-9: Severe Pain (5)10: Worst Pain imaginable

Secondary Outcome Measures

Muscle pressure pain threshold

Muscle pressure pain threshold on bilateral tibialis anterior muscles will be measured by algometer.

Full Information

NCT ID

NCT05165277

First Posted

December 7, 2021

Last Updated

December 7, 2021

Sponsor

Taipei Medical University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05165277

Brief Title

Effect of Flow Rate and pH on Muscle Acidosis

Official Title

Effect of Flow Rate and pH on Muscle Acidosis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Recruiting

Study Start Date

December 15, 2021 (Anticipated)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

January 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Taipei Medical University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This proposed study suggests that peripheral tissue acidosis sensed by the somatosensory system (sngception) 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. In this study, investigators want to determine if there is the correlation between the flow rate of drug application and sng or pain. Also, they try to find if the pH of a solution will affect muscle acidosis.

Detailed Description

Sng is a prominent complaint in Taiwanese people with low back pain. "Sng" is created to represent this Taiwanese word- 痠. Based on our preliminary data, sng was one of the most common complaints in patients with chronic low back pain (CLBP) and also one of the most common indication for lumbar spine operations. Back sng is not adequately relieved by pain-killers or even by the lumbar spine operations. By using functional MRI and questionnaires, our preliminary study demonstrated that sng is different from pain in the level of brain perception and the level of subjective concept. It is very likely that sng has its own unique nerve pathway other than pain. The subjective feeling of sng is very similar to sour in taste, so it is likely that acidosis may be involved in the process of sng sensation, especially in the muscle. Delayed onset muscle soreness is a well-known example, and the soreness is dependent on the proton-sensing neurons. Indeed, substantial evidences showed that up to 80% muscle afferents are acid-sensitive but not nociceptors. Therefore, we propose that sng is the perception in the brain when the tissue acidosis is sensed by the somatosensory system, and "sng-ception" is created to indicate the sensation of tissue acidosis. However, the causal connection between the peripheral sngception and the central brain perception of sng is not established. The objective of this proposal is to establish the causal connection between peripheral muscle acidosis and the central brain sng perception. My central hypothesis is that acidosis-evoked sensation in the muscles will cause a central sng perception in the brain. This hypothesis is based on our previous studies that showed sng is different from pain in terms of subjective responses, brain activation areas and clinical impacts. To achieve this goal, two specific aims will be pursued 1. to determine if an acid solution will evokes sng response, and, 2.determining the correlation between the rate of drug application and muscle Sng. Successful establishment of the casual connection between the peripheral muscle acidosis and the central brain sng perception will lead to a more comprehensive understanding of sng mechanism and the potential medication development.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Muscle Acidosis

Keywords

sngception, soreness, muscle acidosis, flow rate

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Acidic phosphate buffer solution

Arm Type

Experimental

Arm Description

pH5.2 phosphate buffer solution

Arm Title

Neutral phosphate buffer solution

Arm Type

Placebo Comparator

Arm Description

pH7.4 phosphate buffer solution

Intervention Type

Drug

Intervention Name(s)

Phosphate Buffer Solution

Other Intervention Name(s)

Sodium phosphate solution, Phosphate buffered saline

Intervention Description

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).

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Through completion of injection an average of 6 month

Title

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

Description

Time Frame

Through completion of injection an average of 6 month

Secondary Outcome Measure Information:

Title

Muscle pressure pain threshold

Description

Muscle pressure pain threshold on bilateral tibialis anterior muscles will be measured by algometer.

Time Frame

Through completion of injection an average of 1 week

Other Pre-specified Outcome Measures:

Title

36-Item Short Form Health Survey (RAND)

Description

Investigator will evaluate the subject life quality and activity of daily life by 36-Item Short Form Health Survey (RAND) Consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Time Frame

Up to 6 months before signing the informed consent form

Title

Oswestry disability index

Description

Investigator will evaluate the subject activity of daily life by Oswestry disability index The scores for all questions answered are summed, then multiplied by two to obtain the index (range 0 to 100) (1)0 -20: Minimal disability (2)21-40: Moderate Disability (3)41-60: Severe Disability (4)61-80: Crippling back pain (5)81-100: These patients are either bed-bound or have an exaggeration of their symptoms

Time Frame

Up to 6 months before signing the informed consent form

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: The subject has:Neuropathic pain due to causes other than that specified in the inclusion criteria (e.g., post-herpetic neuralgia; painful diabetic neuropathy; mononeuritis multiplex; central poststroke pain; failed back surgery in relation to the presenting episode of radiculopathy; spinal abscess, infection, hematoma, or malignancy; phantom limb pain; peripheral neuropathy due to alcoholism, malignancy, human immunodeficiency virus [HIV], syphilis; drug abuse; vitamin B12 deficiency; hypothyroidism; liver disease; toxic exposure). Pain that is associated with a substantial somatic pain component (e.g., non-neuropathic/musculoskeletal pain in lower limbs or other parts of the body apart from the back) or more than one cause or potential cause for pain symptoms.Any painful concurrent rheumatic disease such as, but not limited to, fibromyalgia, rheumatoid arthritis, or significant osteoarthritis. 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 LSR within 4 weeks before screening. The subject had a malignancy according to his/her report. 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 a history of spinal surgery. The VAS questionnaire not be 0 point either low back "pain" or low back "soreness" assessment. The subject has suffered from claustrophobia. 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.). The subject has mental comorbidity (such as depression, panic disorder, etc) The subject has mental retardation. The educational level of subject is less than 9 years. The subject ,who is unable to understand the purpose of this trial and fill the informed consent.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jiann-Her Lin, MD/PhD

Phone

+886973405133

jiannher@me.com

Facility Information:

Facility Name

Taipei Medical University Hospital

City

Taipei City

ZIP/Postal Code

11031

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiann-Her Lin, MD/PhD

Phone

+886973405133

iannher@me.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

8733302

Citation

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.

Results Reference

background

PubMed Identifier

18835099

Citation

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.

Results Reference

background

PubMed Identifier

30486810

Citation

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.

Results Reference

background

PubMed Identifier

18834667

Citation

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.

Results Reference

background

PubMed Identifier

23490035

Citation

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.

Results Reference

background

PubMed Identifier

24957987

Citation

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.

Results Reference

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Effect of Flow Rate and pH on Muscle Acidosis

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