The Treatment Efficacy of Prolotherapy in Bladder Voiding Dysfunction

Voiding dysfunction including overactive bladder, underactive bladder, and neuropathic bladder. Voiding dysfunction has a great impact on life quality, especially in the elderly society. The current medication for overactive bladder has limited efficacy and the patient easily to dropout the medication because of its side-effects. The underactive bladder is a new entity of voiding dysfunction, its optimal is still unknown. Sacral neuromodulation(SNM) and posterior tibial nerve stimulation(PTNS) have been applied for both overactive bladder and underactive bladder treatment and the results is promising, but the equipment of SNM or PTNS is not available in most places. Prolotherapy using glucose local injection causing inflammatory reaction to stimulate cytokine and growth factors release. Investigators combined the concepts of posterior tibial nerve stimulation and prolotherapy to treat voiding dysfunction. Investigators anticipate it maybe a new promising treatment for voiding dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Overactive Bladder; Underactive Bladder
• Intervention / Treatment: Procedure: prolotherapy

Detailed Description

Inclusion criteria:1. Adults over 20 years-old. 2. The patient who meets the diagnostic criteria of overactive bladder or underactive bladder. 3. The patient who capable to complete 3-days voiding diary and the questionnaire. Exclusion criteria: 1. The patient has severe stress urinary incontinence, severe pelvic organ prolapse, acute urinary tract infection, urolithiasis, or urinary tract malignancy. 2. The patient who has active skin disease on legs or not suitable for leg local injection. 3. Pregnant women. Method: 40 overactive bladder patients and 40 underactive bladder patients. The patients will receive 5% glucose 10ml local injection peripheral to posterior tibial nerve near ankle under ultrasound guidance once a week for 4 weeks, then the patients will be followed up once-a-month for 3 months. OverActive Bladder Symptom Score(OABSS), Core Lower Urinary Tract Symptom score(CLSS) questionnaire, 3-days voiding diary, and urine nerve growth factor are used for assessment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jing-dung Shen, MD; Phone Number: +886958878129; Email: jdwhydo@gmail.com

Study Locations

• Taiwan
  • Other (Non US)
    • Taichung, Other (Non US), Taiwan, 41168
      • Recruiting
      • Taichung Armed Forces General Hospital
      • Contact: Jing-dung Shen, MD; Phone Number: +886958878129; Email: jdwhydo@gmail.com
      • Principal Investigator: Jing-dung Shen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults over 20 years-old.
2. The patient who meets the diagnostic criteria of overactive bladder or underactive bladder.
3. The patient who capable to complete 3-days voiding diary and the questionnaire.

Exclusion Criteria:

1. Severe stress urinary incontinence or severe pelvic organ prolapse.
2. Acute urinary tract infection.
3. Active hematuria, urolithiasis, or neoplasm of urinary tract.
4. Acute skin lesion over the ankle injection site or the patient who could not tolerate ankle injection.
5. Pregnant women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: overactive bladder; Overactive bladder	Procedure: prolotherapy; 5% glucose 10ml local injection peripheral to posterior tibial nerve near ankle under ultrasound guidance once a week for 4 weeks.
Experimental: Underactive bladder	Procedure: prolotherapy; 5% glucose 10ml local injection peripheral to posterior tibial nerve near ankle under ultrasound guidance once a week for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week 0
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week1
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week2
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week3
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week4
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week8
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week12
Overactive Bladder Symptom Score	The improvement of overactive bladder symptom score (OABSS), OABSS ranged from 0 to 15, the higher score means more severity of overactive bladder.	Week16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cystometric bladder capacity	Cystometric bladder capacity: the volume of water instilled into bladder while performing cystometry examination.	Week0
Cystometric bladder capacity	Cystometric bladder capacity: the volume of water instilled into bladder while performing cystometry examination.	Week4
Cystometric bladder capacity	Cystometric bladder capacity: the volume of water instilled into bladder while performing cystometry examination.	Week16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The improvement of Patient Perception of Bladder Condition (PPBC)	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week 0
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week1
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week2
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week3
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week4
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems.	Week8
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Ranged from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week12
The improvement of Patient Perception of Bladder Condition	The PPBC measures the patients' perception of their urinary (bladder) problems. Range from 1 to 6. The core 1 means no bother from bladder condition, higher score means more bother form bladder condition.	Week16

Collaborators and Investigators

• Sponsor: Taichung Armed Forces General Hospital
• Investigators: Principal Investigator: Jing-dung Shen, Taichung Armed Forces General Hospital

Publications and helpful links

General Publications

• Gormley EA, Lightner DJ, Faraday M, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015 May;193(5):1572-80. doi: 10.1016/j.juro.2015.01.087. Epub 2015 Jan 23.
• Wu YT, Ho TY, Chou YC, Ke MJ, Li TY, Tsai CK, Chen LC. Six-month Efficacy of Perineural Dextrose for Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial. Mayo Clin Proc. 2017 Aug;92(8):1179-1189. doi: 10.1016/j.mayocp.2017.05.025.
• Tsui BCH, Kropelin B. The electrophysiological effect of dextrose 5% in water on single-shot peripheral nerve stimulation. Anesth Analg. 2005 Jun;100(6):1837-1839. doi: 10.1213/01.ANE.0000153020.84780.A5.
• Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008 Jun;9(6):453-66. doi: 10.1038/nrn2401.
• Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med. 2002 Mar 5;136(5):374-83. doi: 10.7326/0003-4819-136-5-200203050-00010.
• Abraham TS, Chen ML, Ma SX. TRPV1 expression in acupuncture points: response to electroacupuncture stimulation. J Chem Neuroanat. 2011 Apr;41(3):129-36. doi: 10.1016/j.jchemneu.2011.01.001. Epub 2011 Jan 20.
• Chen HC, Chen MY, Hsieh CL, Wu SY, Hsu HC, Lin YW. TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and Central Nerve System. Cell Physiol Biochem. 2018;49(5):1813-1824. doi: 10.1159/000493627. Epub 2018 Sep 19.
• Zhang T, Yu J, Huang Z, Wang G, Zhang R. Electroacupuncture improves neurogenic bladder dysfunction through activation of NGF/TrkA signaling in a rat model. J Cell Biochem. 2019 Jun;120(6):9900-9905. doi: 10.1002/jcb.28272. Epub 2018 Dec 28.
• Zhao Y, Zhou J, Mo Q, Wang Y, Yu J, Liu Z. Acupuncture for adults with overactive bladder: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018 Feb;97(8):e9838. doi: 10.1097/MD.0000000000009838.
• MacDiarmid SA, Peters KM, Shobeiri SA, Wooldridge LS, Rovner ES, Leong FC, Siegel SW, Tate SB, Feagins BA. Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder. J Urol. 2010 Jan;183(1):234-40. doi: 10.1016/j.juro.2009.08.160.
• Sakura S, Chan VW, Ciriales R, Drasner K. The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administered intrathecally in the rat. Anesthesiology. 1995 Jan;82(1):236-40. doi: 10.1097/00000542-199501000-00028.
• Tsui BC, Kropelin B, Ganapathy S, Finucane B. Dextrose 5% in water: fluid medium for maintaining electrical stimulation of peripheral nerves during stimulating catheter placement. Acta Anaesthesiol Scand. 2005 Nov;49(10):1562-5. doi: 10.1111/j.1399-6576.2005.00736.x.
• Peters KM, Carrico DJ, Perez-Marrero RA, Khan AU, Wooldridge LS, Davis GL, Macdiarmid SA. Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. 2010 Apr;183(4):1438-43. doi: 10.1016/j.juro.2009.12.036. Epub 2010 Feb 20.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 17, 2022
• First Submitted That Met QC Criteria: July 31, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 27, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: overactive bladder; detrusor underactivity; neural prolotherapy
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Urinary Bladder, Underactive
• Other Study ID Numbers: 108B01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No