Clinical Research on the Efficacy of Bosinji on Herniated Intervertebral Disc of Lumbar Spine

Seventy-four patients between the ages of 19 and 70 with L-HIVD will be recruited by eligibility criteria and randomly allocated to the experimental group and the control group. In the experimental group, 2.5g of Bosinji granule (Tsumura \& Co., Tokyo, Japan) will be orally administered three times a day at 30 minutes after the meal for 6 weeks. In the control group, Loxonine tab. (loxoprofen 60mg, Dong Wha Pharm Co., Ltd, Seoul, Korea) will be orally administered in the same usage and period with the experimental group. In addition, both group will receive the same acupuncture treatment on 20 acupoints once a week for 6 weeks. 100 mm visual analogue scale (VAS) for low back pain will be assessed as a primary outcome at baseline and treatment end. Also, 100mm VAS for radiating pain, Oswestry disability index (ODI), Rolland Morris disability questionnaire (RMDQ), EQ-5D-5L and global perceived effect (GPE), Deficiency Syndrome of Kidney Index (DSKI) will be measured as secondary outcomes at baseline, 3 weeks after screening, treatment end (6 weeks, primary endpoint) and follow-up sessions (10 weeks).

• Bosinji (Drug), also known as Ucha-Shinki-Hwan: Product name : Bosinji Granule Manufacturer : Tsumura \& Co. Ingredient : Bosinji granule 2.5g (Bosinji extract 1.523g) Bosinji extract is composed of following proportion of ingredient * Rehmannia Root 1.7g * Achyranthes Root 1.0g * Cornus Fruit 1.0g * Dioscorea Rhizome 1.0g * Psyllium Husk 1.0g * Alisma Rhizome 1.0g * Hoelen 1.0g * Moutan Root Bark 1.0g * Cinnamon Bark 0.3g * Pulvis Aconiti Tuberis Purificatum 0.3g
• Loxonine tab. (Drug), also known as Loxoprofen: Product name : Loxonine tab. Manufacturer : Dong Wha Pharm. Co., Ltd Ingredient : Loxoprofen Sodium 68.1mg (Loxoprofen 60mg)
• Acupuncture (Procedure): Acupuncture treatment will be performed on 20 predefined acupoint using 0.25mm x 40mm acupuncture needle. The time for needle retaining is 15 minutes. 1. Both EX-B2 of herniated intervertebral disc level, its upper level and its lower level (6 acupoints) 2. Both side BL24, BL25, BL26, EX-B7, BL28 (10 acupoints) 3. Symptomatic side GB30, GB34, BL57, ST36 (4 acupoints)

Primary outcomes

• Change from Baseline 100mm Pain Visual Analogue Scale (VAS) for low back pain at Week 6 [Week 0 (Baseline), Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Measurement instrument for subjective pain

Secondary outcomes

• 100mm Pain Visual Analogue Scale (VAS) for radiating pain [Week 0 (Baseline), Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Measurement instrument for subjective pain
• Oswestry Disability Index (ODI) [Week 0 (Baseline), Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Validated questionnaire for disability of low back pain
• EuroQol-5 dimensions-5 level (EQ-5D-5L) [Week 0 (Baseline), Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Standardized instrument for generic health status
• Roland-Morris Disability Questionnaire (RMDQ) [Week 0 (Baseline), Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Health status measure for low back pain
• Global Perceived Effect (GPE) [Week 3, Week 6 (Primary end point, Treatment end), Week 10 (F/U)]: Assessment of change in the patient's chief complaint
• Deficiency Syndrome of Kidney Index (DSKI) [Week 0 (Baseline), Week 6 (Primary end point, Treatment end)]: Questionnaire for assessing symptoms related to deficiency syndrome of kidney

Sex: All, ages: 19 Years to any

Inclusion Criteria:

1. Men or women aged over 19 years
2. Radiating pain matched with severer abnormality than bulging shown by CT or MRI on lumbar spine
3. low back pain between 40 and 80 point on 100mm pain visual analogue scale
4. Volunteers who agree to participate and sign the Informed Consent Form, following a detailedexplanation of clinical trials

Exclusion Criteria:

1. Congenital abnormalities or surgical history on lumbar regions
2. Red flag signs that may be suspected of cauda equina syndrome, such as bladder and bowel dysfunction or saddle anesthesia
3. Tumor, fracture or infection in lumbar regions
4. Injection treatment on lumbar regions within 1 week
5. Psychiatric disorder currently undergoing treatment such as depression or schizophrenia
6. Liver function abnormality (AST or ALT over 2times normal range)
7. Renal fuction abnormaility (Serum creatinine > 2.0㎎/㎗)
8. Other diseases that could affect or interfere with therapeutic outcomes, including severe gastrointestinal disease, cardiovascular disease, hypertension, diabetes, renal disease, liver disease or thyroid disorder
9. Contraindication of NSAIDs including intercurrent disease, hypersensitivity reaction or other medication
10. Inappropriate condition for acupuncture due to skin disease or hemostatic disorder (PT INR > 2.0 or taking anticoagulant)
11. Women who is pregnant, breastfeeding or having pregnancy plan
12. Other inappropriate condition for herbal medicine treatment
13. participation in other clinical trial with 1 month

• Results publication: Goo B, Kim JH, Kim EJ, Nam D, Lee HJ, Kim JS, Park YC, Baek YH, Nam SS, Seo BK. Clinical research on the effectiveness and safety of Uchasingihwan for low back pain with radiculopathy caused by herniated intervertebral disc of the lumbar spine: A multicenter, randomized, controlled equivalence trial. Integr Med Res. 2024 Dec;13(4):101090. doi: 10.1016/j.imr.2024.101090. Epub 2024 Sep 30. PMID 39640075
• Results publication: Goo B, Kim SJ, Kim EJ, Nam D, Lee HJ, Kim JS, Park YC, Baek YH, Nam SS, Seo BK. Clinical research on the efficacy and safety of Bosinji for low back pain with radiculopathy caused by herniated intervertebral disc of the lumbar spine: A protocol for a multicenter, randomized, controlled equivalence trial. Medicine (Baltimore). 2018 Dec;97(50):e13684. doi: 10.1097/MD.0000000000013684. PMID 30558079

• Byung-Kwan Seo, PhD., KMD, Principal investigator, Kyunghee University Medical Center