Efficacy and safety assessment of orthopedic device (LSM-01) for low back pain: A randomized, single-blinded, sham-controlled, parallel-group, pilot clinical trial.

BACKGROUND: Low back pain refers to pain that occurs mainly in lumbosacral spine, and is a clinically common symptom that 70% to 90% of people experience at least once during their lives. OBJECTIVES: We investigated the effect and safety of orthopedic device (LSM-01) for alleviate back pain caused by muscle tension in a randomized, single-blinded, sham-controlled, parallel-group, pilot trial to establish a basis for large-scale clinical trial. METHODS: A total of 30 subjects were randomly assigned to 2 group: treatment group (LSM-01) and control group (sham device) received treatment with each device 2 to 3 times a week for a total of 6 treatment for 2 weeks. Primary outcome was visual analog scale (VAS); Secondary outcomes were pressure pain threshold (PPT), oswestry disability index (ODI), and patient global impression of change (PGIC). Statistical analysis is performed for full analysis set (FAS) population. Analysis of covariance (ANCOVA) for mean difference of VAS change and Mixed models of repeated measurements (MMRM) for the trend of VAS change were conducted to compare the differences between 2 groups before and after participants got treatment with the clinical trial device. RESULTS: One participant dropped out due to personal reason and 29 participants completed the clinical pilot trial. We found that the degree of low back pain (VAS, PPT, PGIC) significantly decreased and after the trial in the treatment group compared to the control group. Also, there were no any side effects. CONCLUSION: LSM-01 can be effective in improving pain of low back pain. A future large-scale main trial will be conducted based on this pilot study results.

Efficacy of Phellinus linteus extract on immunity enhancement: A CONSORT-randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: Immunity is a major system that defends the human body from the outside. Recently, interest in foods related to immunity has been increasing. METHODS: The purpose of this clinical trial was to determine the safety and efficacy of Phellinus linteus (PL) extract in improving immune function. A total of 30 participants were randomly assigned to 3 groups: the PL1000 group (n = 10) took 1000 mg of PL extract and 1000 mg of dextrin per day; the PL2000 group (n = 10) took 2000 mg of PL extract per day; and the placebo group (n = 10) took 2000 mg of dextrin per day. All participants took 2 capsules twice a day for 8 weeks. We measured their natural killer cell activity and cytokine levels in blood before and after consuming the clinical trial food. Variables were also investigated to evaluate safety, such as adverse reactions, vital signs, and abnormal findings. Student t test or the Mann-Whitney U test, a paired t test or the Wilcoxon signed-rank test, a chi-square test, analysis of variance, and Kruskal-Wallis test were conducted according to the characteristics of the data to compare the differences between each group before and after participants ate the clinical trial food. RESULTS: The natural killer cell activity and interleukin-6 levels of the PL1000 group tended to improve compared to those of the placebo group. Immunoglobulin G1, immunoglobulin G2, and immunoglobulin M levels did not show significant changes, but tended to improve in the PL1000 and PL2000 groups compared to those of the placebo group. Both the Per Protocol and Intention to Treat populations had improved validation parameters. It is safe because no hazards were found in the safety assessment. CONCLUSION: PL extract can help improve immunity. Evidences to conduct the main clinical trial is secured through this pilot study. A future large-scale main trial will be conducted based on this pilot study results.

Efficacy of Liriope platyphylla extract on improving respiratory function: A CONSORT-randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: The respiratory system is the first line of defense against outside pollutants. Recently, respiratory health has been receiving increasing attention due to the increase in fine dust, which reduces respiratory function and increases incidence of chronic obstructive pulmonary disease, and in coronavirus pandemic, which can cause severe acute respiratory syndrome. METHODS: This clinical pilot trial was designed to secure evidence for a main clinical trial and to confirm the efficacy and safety of Liriope platyphylla (LP) extract for improving respiratory function. We conducted a double-blind randomized placebo-controlled trial with 22 participants from June 30, 2021, to August 25, 2021. The primary outcome was Breathlessness, Cough, and Sputum Scale score. Secondary outcomes included forced vital capacity, forced expiratory volume at 1 second (FEV1), forced expiratory volume at 1 s/forced vital capacity ratio, cough assessment test score, chronic obstructive pulmonary disease assessment test score, peripheral blood mononuclear cell counts (white blood cells, eosinophils, T cells, and B cells), high-sensitivity C-reactive protein level, erythrocyte sedimentation rate, cytokine (interleukin-1ß, interleukin-4, tumor necrosis factor-α, interleukin-6, interleukin-8, interferon-γ, and immunoglobulin E) levels, antioxidant (glutathione peroxidase and superoxide dismutase) levels, and nitric oxide level. RESULTS: A total of 22 participants were randomly assigned to 2 groups: the LP group (n = 11), who took 1000 mg of LP extract per day, and the placebo group, who took 1000 mg of dextrin per day. Participants took 1 capsule twice a day for 4 weeks. For the Breathlessness, Cough, and Sputum Scale, the interaction between group and visit was statistically significant in a blend of analyses of variance. interleukin-8, tumor necrosis factor-α, and interferon-γ levels decreased more in the LP group than in the placebo group. The sample size required for large-scale clinical trials in the future was 50. There were no side effects. CONCLUSION: LP extract can enhance respiratory function. The detailed data we obtained support conducting the future main large-scale clinical trial.

Effects of Phellinus linteus extract on immunity improvement: A CONSORT-randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Immunity protects the body from external threats and prevents the development of cancer. Biological response modifiers extracted from natural sources are being actively studied, and the immunostimulatory and anticancer effects of various types of fungi have been reported. However, there are no previous clinical studies on the immune-enhancing effect of Phellinus linteus (PL). Lactate dehydrogenase cytotoxicity assay is a prerequisite in order to get approval for using PL as a raw material in functional supplements and medicines in Korea. However, due to the absence of precedent clinical trials, the use of PL in supplements has been hindered. but there is no precedent clinical trial using it. We conducted a randomized, double-blinded, placebo-controlled trial to confirm the efficacy and safety of PL extract for the improvement of immunity using the lactate dehydrogenase cytotoxicity assay. METHODS: A total of 98 subjects were enrolled and randomly assigned to 2 groups. Subjects in the PL and placebo groups received 1000 mg of PL extract and 1000 mg of dextrin per day, respectively (one capsule, twice every day for 8 weeks). The primary outcome measured was the activity of natural killer cells. Secondary outcomes were the levels of TNF-α, IFN-γ, IL-1ß, IL-2, IL-6, IL-12, IgG1, IgG2, and IgM. Safety was evaluated using laboratory tests. RESULTS: NK cell activity was significantly increased in the PL group compared to the placebo group (P < .05). Despite the absence of significant changes in secondary outcomes, there was a tendency for improvement in the PL group. PL extract-related adverse outcomes, particularly in liver and renal function, were not observed. CONCLUSION: PL extract may improve immunity and is safe to be consumed orally.

Efficacy of liriope platyphylla extract for improving respiratory functions: Study protocol for a randomized, double-blinded, placebo-controlled pilot trial.

BACKGROUND: Respiratory disease has emerged as a global issue due to COVID-19. In particular, there has been an increased frequency of occurrence of symptoms such as cough, sputum, and dyspnea, which commonly accompany chronic obstructive pulmonary disease (COPD). Liriope platyphylla (LP) extract is known to improve respiratory function. LP extract ameliorates the symptoms commonly seen in bronchitis, asthma, and COPD and enhances immunity, as it has anti-inflammatory properties. In a previous study in rats, LP effectively improved respiratory inflammation levels. However, few randomized controlled trials have verified the effects of LP in respiratory disease and there have been no studies to determine the appropriate dose and duration to make it a more convenient functional health product. Based on previous studies, we would like to proceed with this clinical trial under the assumption that LP will help improve respiratory function and produce anti-inflammatory effects. METHODS: This will be a single-center, randomized, double-blind, placebo-controlled pilot trial. Participants will randomly be allocated to receive either 1000 mg LP or placebo. The total duration of the clinical trial will be 4 to 6 weeks. A follow-up assessment will be conducted 4 weeks after screening, and the effect and safety of LP application will be assessed at this second visit. The primary outcome will be the breathlessness, cough, and sputum scale score. Secondary outcomes will include pulmonary function, clinical symptoms of cough and sputum (reported through a questionnaire), changes in immune cells, changes in immune factors used to analyze allergic inflammation in bronchi, antioxidant enzyme activity, nitric oxide level, and COPD assessment test score. DISCUSSION: This study has limited inclusion and exclusion criteria and the intervention will be well-controlled. This will be the first randomized controlled trial to assess the efficacy and safety of LP extract in adults with cough and sputum. This study will provide insight into the mechanisms of the anti-inflammatory effects and improvement of respiratory function of LP.

Effectiveness and safety assessment of orthopedic device (LSM-01) for low back pain: A randomized, single-blinded, sham-controlled, parallel-group, pilot clinical trial.

BACKGROUND: More than 80% of the population suffer from low back pain at some time during their lives. An orthopedic device (LSM-01) will be used to alleviate back pain caused by muscle tension. LSM-01, which has a rotating roller, stimulates meridian-muscles around the governor vessel, bladder meridian, and gall bladder meridian. METHODS: This study will be a randomized, single-blinded, sham-controlled, parallel-group, pilot clinical trial. Subjects will be randomly allocated to the treatment group (LSM-01) or the control group (sham device). The duration of the clinical trial will be 2 weeks. The primary outcomes will be measured using the visual analog scale; the secondary outcomes will include pressure pain threshold, Oswestry Disability Index, and Patient Global Impression of Change. Statistical analysis will be performed for the full study population. Analysis of covariance will be conducted to identify differences in pain before and after the application of the device. DISCUSSION: This clinical trial will evaluate the safety and efficacy of the LSM-01 device. As a pilot study, this investigation includes a limited number of subjects. The results of this pilot trial will form a basis for a large-scale clinical trial, which will be conducted in the future. CLINICAL TRIAL REGISTRATION: This study protocol is registered with the Clinical Research Information Service (CRIS) of Korea. Clinical trial registration number: CRIS-KCT0006425. Registered: October 5, 2021; https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&search_page=L&pageSize=10&page=undefined&seq=20056&status=5&seq_group=20056.

Clinical trial to analyze the effects of oral intake of Phellinus linteus (sanghuang) extract on immune function: a study protocol for a randomized, double-blind controlled trial.

BACKGROUND: As the population of Korea ages, interest in healthcare has increased. In particular, there is an increasing demand for immune-function improvement to prevent infectious diseases. Phellinus linteus (PL) has previously been shown to exert immune-enhancing and anticancer effects. We aim to evaluate whether PL mycelium extract, cultured from the PL KCTC0399BP strain, can increase immune function, as measured using blood-test indicators. This clinical trial protocol is designed as the main trial and is based on the results of a pilot study. METHODS: This clinical trial is a randomized, double-blinded, placebo-controlled trial. Ninety-eight participants are enrolled and randomly divided into two groups: the experimental group (PL 1000 mg) and the control group (placebo). Participants are administered with experimental food or placebo for eight weeks. Blood tests are performed before trial initiation and 8 weeks later, at trial completion. Laboratory evaluation items are as follows: natural killer cell activity, tumor necrosis factor-α, interferon-γ, interleukin (IL)-1ß, IL-2, IL-6, IL-12, immunoglobulin (Ig)G1, IgG2, and IgM. We will mainly use the full analysis dataset to statistically analyze the effectiveness of the treatment. DISCUSSION: This study evaluates the effects of PL extract on immune function and will contribute to knowledge on the value of PL as an immune-function-boosting functional food. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) of Korea CRIS-KCT0005460 . Registered on 12 October 2020.

Effect of Bee Venom on an Experimental Cellular Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease and is characterized by the deposition of the [Formula: see text]-Amyloid peptide ([Formula: see text]A), which causes the inflammation of neurons. Bee venom (BV) elicits a strong anti-inflammatory response, and therefore we conducted an in vitro experiment to study the efficacy of BV in an AD cellular model. To mimic AD, the U87MG cell line was incubated for 168 hours with 2.5 [Formula: see text]M [Formula: see text]A. Changes were confirmed by microscopy, and peptides were measured under stain-free conditions using homo-tomography. Sulforhodamine B analysis was performed to analyze the cell viability. Real-Time quantitative polymerase chain reaction (qPCR) analysis was conducted to analyze mRNA expression levels of pro-inflammatory cytokines (NF-[Formula: see text]B, COX-2, TNF-[Formula: see text], IL-1), and Western blot was performed to measure the Caspase-3 protein levels. BV showed no cytotoxicity at concentrations below 10 [Formula: see text]g/mL. The NF-[Formula: see text]B mRNA levels were not significantly different between the BV group and the control group. The amount of [Formula: see text]A accumulation in the BV group decreased significantly. The mRNA expression levels of COX-2, TNF-[Formula: see text], and IL-1 were significantly reduced using 10 [Formula: see text]g/mL of BV compared to those in the control group. Additionally, Caspase-3 levels were also reduced compared to those of the control group when BV was used at a concentration of 10 [Formula: see text]g/mL. BV could inhibit apoptosis and inflammatory responses in an AD cellular model. In addition, it prevented cell accumulation of [Formula: see text]A, an important pathogenic mechanism in AD.

Acupotomy versus Manual Acupuncture for the Treatment of Back and/or Leg Pain in Patients with Lumbar Disc Herniation: A Multicenter, Randomized, Controlled, Assessor-Blinded Clinical Trial.

BACKGROUND: Acupotomy, which involves the addition of a scalpel function to the conventional acupuncture treatment, has recently been applied as a conservative treatment method for lumbar disc herniation (LDH). This study investigated the effectiveness and safety of acupotomy, compared to manual acupuncture, for the treatment of patients with LDH. METHODS: A total of 146 patients diagnosed with LDH were randomly assigned to either the acupotomy group or the manual acupuncture group at a 1:1 ratio. Participants in both groups received four sessions of each intervention over 2 weeks. Outcome assessments based on the visual analog scale (VAS), Roland Morris Disability Questionnaire (RMDQ), Modified-Modified Schober Test (MMST), EuroQol Five Dimensions (EQ-5D), clinically important difference (CID), and patient global impression of change (PGIC) were conducted at baseline and at 2, 4, and 6 weeks post-randomization. RESULTS: The acupotomy group showed significant improvement in VAS and MMST at 2, 4, and 6 weeks than did the manual acupuncture group. RMDQ was significantly different between the two groups at 2 and 6 weeks. In EQ-5D, there was no significant difference between the two groups. The proportion of patients with ≥15 mm decrease on the VAS (minimal CID) was significantly higher in the acupotomy group at weeks 2 and 4. Better improvement in the PGIC at week 4 was also observed in the acupotomy group. Post-intervention muscle pain was reported, but there was no serious adverse event related to interventions. CONCLUSION: In this study, four sessions of acupotomy treatment were found to be effective in improving the pain intensity and range of motion of the lumbar region in patients with LDH. Despite post-treatment muscle pain, acupotomy treatment can be considered a preferred treatment method over manual acupuncture. TRIAL REGISTRATION: This trial has been registered 24 April 2018 in Clinical Research Information Service of South Korea (CRIS-KCT0002824).

A clinical pilot study to evaluate the efficacy of oral intake of phellinus linteus (sanghuang) extract on knee joint and articular cartilage: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of degenerative arthritis. We used Phellinus linteus (PL), which has been well-known anti-inflammatory function. In this study, we will evaluate if PL extract improves symptoms with KOA. METHODS: This study will be an 8-week single-center randomized controlled double-blind clinical trial. Total of 24 subjects with KOA will be enrolled and they will be divided into 3 groups, PL 1,000 mg, PL 1,500 mg and placebo. Subjects will be followed up every 4 weeks with efficacy and safety at the 2nd and 3rd visits. All subjects should maintain a dosage schedule for this protocol. The primary outcome will be assessed with the Korean version of the Western Ontario and McMasters Universities. And the secondary outcomes will be measured using the visual analog scale, quality of life scale (EQ-5D-3L), ESR, C-reactive protein, and C-telopeptide of type-II collagen. Statistical analysis will be performed on the principle of full analysis set. DISCUSSION: This study has inclusion and exclusion criteria and a well-controlled intervention. This clinical trial is the first step to assess the efficacy and safety of PL in patients with KOA. This study will make an important contribution to the literature and aid follow-up research into the use of PL in KOA.

Efficacy of Phellinus linteus (sanghuang) extract for improving immune functions: Study protocol for a randomized, double-blinded, placebo-controlled pilot trial.

BACKGROUND: With the increase in the prevalence of chronic diseases, enhancing immunity has become an important challenge. Health functional foods, such as Phellitus linteus (PL), are known to improve immune function. In previous laboratory studies, it has been reported that PL has anticancer activities. In this study, we will evaluate if PL improves immune functions in adults with reduced immunity and identify its effects on immunity factors. METHODS: This study will be a single-center, randomized, double-blinded, and placebo-controlled trial. Study participants will be randomly allocated to 3 experimental groups: those taking PL 1000 mg, PL 2000 mg, or placebo. Total duration of the clinical trial will be 8 to 10 weeks. Study participants will have follow-up visits every 4 weeks and the effect and safety will be assessed at the second and third visits. All participants will be asked to maintain a dosage schedule for this protocol. The primary outcome will be natural killer (NK) cell activity and the secondary outcomes will include peripheral white blood cell (WBC) count; levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1ß, IL-2, IL-6, and IL-12 to assess autoimmune reactivity; and levels of immunoglobulin (Ig)G1, IgG2, and Immunoglobulin M (IgM) to assess allergic activity. Repeated measure analysis will be used to measure primary efficacy based on full analysis set. DISCUSSION: This study has limited inclusion and exclusion criteria and a well-controlled intervention. It will be the first randomized controlled trial to assess the efficacy and safety of PL in adults with reduced immunity. This study will provide insights into the mechanisms underlying the immune-stimulating effects of PL and lay the groundwork for further studies.

Efficacy of Juglandis semen complex extract for knee osteoarthritis: A pilot study protocol for a 12-week, single-center, randomized, controlled, double-blind clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common disease in elderly individuals. Many medications for KOA have the potential to cause side effects. We used Juglandis semen complex extract (JCE) consisting of 4 herbs derived from Cheong-A-Won, which has been commonly used for KOA treatment. In this study, we will evaluate whether JCE improves symptoms in patients with KOA and will identify the changes in the inflammation factor. METHODS: This study will be a single-center, randomized, double-blind, and placebo-controlled trial. Three groups, JCE 1000 mg, 2000 mg, and placebo, will be randomly allocated. Total duration of the clinical trial will be 12 to 14 weeks. Study participants will be followed up every 6 weeks and the effect and safety will be assessed at the 2, 3, and 4 visit. All participants were asked to maintain a dosage schedule for this protocol. The primary outcomes will be measured using Korean Western Ontario and McMaster Universities Questionnaire and the secondary outcomes will include pain Visual analog scale score, EuroQol Five Dimensions questionnaire, Patient Global Impression of Change, and the changes in the laboratory test parameters of inflammation. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set. DISCUSSION: This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to assess the efficacy and safety of JCE in patients with KOA. This study provides insights into the mechanisms that explain the therapeutic effects of JCE in KOA and will lay the groundwork for further studies.

Efficacy and safety of electromagnetic acupuncture using an electromagnetic therapy stimulator (Whata153) for the treatment of chronic low back pain: Study protocol for a single-center, parallel-arm, randomized clinical trial.

BACKGROUND: Chronic low back pain is one of the major conditions causing serious personal and social difficulties in modern society. There are several noninvasive therapies for chronic low back pain; however, the effects of electromagnetic acupuncture have not been studied. Here, we describe the protocol for a study that will investigate the efficacy and safety of electromagnetic acupuncture for patients with chronic low back pain. METHODS: The study has been designed as a double-blind, single-center, parallel-arm, sham-controlled, randomized clinical trial. A total of 104 patients with chronic low back pain who meet the criteria for selection and exclusion will be enrolled in a 1:1 ratio in an electromagnetic acupuncture group or a sham group. Sterilized disposable needles will be inserted at 6 acupoints, following which stimulation via an electromagnetic (Whata153) or a placebo (sham) stimulator will be applied. The 2 groups will receive a total of 6 treatment sessions over 3 weeks, with 1 follow-up visit within 3 days after the final treatment. The primary outcome will be the change in the visual analog scale (VAS) score for pain from baseline (visit 1, first treatment session) to the follow-up visit (visit 7, after treatment completion). The secondary outcomes will be as follows: changes in the VAS score for pain from baseline (visit 1) to visits 3 (third session) and 5 (fifth session); changes in the VAS score for pain at all assessment points from baseline (visit 1) to the follow-up visit (visit 7); changes in the Oswestry Disability Index (ODI) from visit 1 to visits 3, 5, and 7; and the change in ODI at all assessment points from visit 1 to visit 7. DISCUSSION: The results of this trial are expected to provide important clinical information on the efficacy and safety of electromagnetic acupuncture for patients with chronic low back pain.

Effectiveness and safety of acupotomy for treating back and/or leg pain in patients with lumbar disc herniation: A study protocol for a multicenter, randomized, controlled, clinical trial.

BACKGROUND: As the number of patients suffering from back and/or leg pain due to lumbar disc herniation (LDH) is increasing in Korea, conservative treatments for patients with LDH have been spotlighted. Although several studies have been published on the use of acupotomy for the treatment of such patients, most of them are only case studies. Therefore, the purpose of this study is to compare the effectiveness and safety of acupotomy to those for manual acupuncture for the treatment of patients with LDH. METHODS/DESIGN: This study is planned as a multicenter, parallel design, randomized, controlled, clinical study. One hundred forty-six patients diagnosed with LDH will be randomly assigned to either the acupotomy group or the manual acupuncture group at a 1:1 ratio. Participants in both groups will receive a total of 4 interventions over 2 weeks. An effectiveness assessment based on the outcomes on the visual analog scale (VAS), Roland Morris Disability Questionnaire (RMDQ), Modified-Modified Schober Test (MMST), EuroQol Five Dimensions (EQ-5D), and Patient Global Impression of Change (PGIC) will be conducted at baseline and at 2, 4, and 6 weeks postrandomization. The primary outcome will be the mean change in the VAS for back and/or leg pain 4 weeks postrandomization. Adverse events will be recorded at every visit. DISCUSSION: The results of this study will provide evidence for the effectiveness and safety of acupotomy treatment for patients with LDH. TRIAL REGISTRATION: Clinical Research Information Service of South Korea (CRIS- KCT0002824), April 24, 2018.

Short-Term Effect of Laser Acupuncture on Lower Back Pain: A Randomized, Placebo-Controlled, Double-Blind Trial.

Purpose. This trial was performed to investigate the efficacy of laser acupuncture for the alleviation of lower back pain. Methods. This was a randomized, placebo-controlled, double-blind trial. Fifty-six participants were randomly assigned to either the laser acupuncture group (n = 28) or the sham laser acupuncture group (n = 28). Participants in both groups received three treatment sessions over the course of one week. Thirteen acupuncture points were selected. The visual analogue scale for pain, pressure pain threshold, Patient Global Impression of Change, and Euro-Quality-of-Life Five Dimensions questionnaire (Korean version) were used to evaluate the effect of laser acupuncture treatment on lower back pain. Results. There were no significant differences in any outcome between the two groups, although the participants in both groups showed a significant improvement in each assessed parameter relative to the baseline values. Conclusion. Although there was no significant difference in outcomes between the two groups, the results suggest that laser acupuncture can provide effective pain alleviation and can be considered an option for relief from lower back pain. Further studies using long-term intervention, a larger sample size, and rigorous methodology are required to clarify the effect of laser acupuncture on lower back pain.