Intravesical Injection of Dextrose to Improve Lower Urinary Tract Symptoms Caused by Chronic Cystitis

April 1, 2021 updated by: Juin-Hong Cherng, National Defense Medical Center, Taiwan

The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. Scholars have put forward different hypotheses, including the function of the extracellular matrix surface of the glycosaminoglycan (GAG) layer, downregulation of tight junction protein, increased urothelial permeability, mast cell activation, neurogenic inflammation, and psychosomatic factors. The symptoms are very similar to severe bladder pain syndrome/interstitial cystitis, and the patients respond to existing medications. In 1956, Dr. George Hackett created a method for treating damaged ligaments and tendons called prolotherapy (proliferation therapy). Prolotherapy is defined as an alternative therapy for musculoskeletal and arthritic pain, including the treatment of irritating substances (such as dextrose, also known as d-glucose) injected into ligaments or tendons to promote the growth of new tissues. There are many clinical trials confirming that proliferation therapy can effectively treat painful musculoskeletal problems. For example, in patients with lateral epicondylitis treated with a solution with a final concentration of 10% dextrose, compared with patients treated with placebo (normal saline), pain and isometric muscle strength improved significantly. A recent literature review also tells that hypertonic glucose proliferation therapy can effectively treat a variety of musculoskeletal diseases.

Hence, this research suggests that dextrose prolotherapy is an affordable and effective pain management strategy in dealing with musculoskeletal neuroinflammation pain in BPS/IC. In order to begin to understand prolotherapy and its therapeutic utility, this study should begin to elucidate the immediate response of prolotherapy in the urology field by investigating the impact of dextrose.

This project is expected to accommodate subjects with BPS/IC, by injecting 10% dextrose into the bladder lining muscles of IC patients and performing various urodynamic tests and questionnaires to evaluate the patient's urinary voiding symptoms and urinary bladder function recovery. Afterward, the expressions of growth factors and cytokines in the urine samples were investigated in an attempt to reveal the mechanism of dextrose prolotherapy in BPS/IC disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This project treated 29 male and female subjects (aged over 20 years) with BPS/IC and other chronic inflammation of the bladder. The enrolled subjects were collected from May 2019 to October 2020. The subjects were given intravesical injections of 10% dextrose under intravenous general anesthesia in the operating room: 2 mL of 50% Dextrose (Vitagen Inj., Taiwan Biotech co. ltd., Taipei, Taiwan) was briefly diluted with 10 mL of normal saline and 11 sub urothelial injections (1 mL each site) were performed. The injection needle was inserted into the urothelium at the trigone (1 site), the posterior (6 sites), and the lateral walls (4 sites) of the bladder, using a 23-gauge needle under rigid cystoscopic injection instrument (22-Fr; Knittlingen, Richard Wolf, Germany). No post-injection analgesics were provided to patients. Treatment was repeated based on the patients' condition once every 2 weeks for the first 6 cycles and once every month for the remaining 3 cycles with a maximum of 9 planned therapy cycles up to 6 months. The patients would be followed-up and assessed at each treatment time and up to 1 month after the last treatment. 19 health subjects were also recruited as a healthy control as the comparison.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei city, Taiwan, 114
        • National Defense of Medical Center, Tri-Service General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The subject is aged over 20 years old.
  2. The subject was diagnosed as bladder pain syndrome/interstitial cystitis subject with lower urinary tract symptoms, such as frequent urination, urgent urination, bladder pain, etc.

Exclusion Criteria:

  1. The subject is aged under 20 years old.
  2. Pregnant women.
  3. The subject with congenital disorders of the urinary tract.
  4. The subject with a urinary tract infection or tumor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Healthy participant
Experimental: Dextrose treatment
IC/PBS patients had been treated by intravesical instillations of hyaluronic acid and/or botox for more than 6 months
Drug: Dextrose
10% dextrose: 2 mL of 50% dextrose in 10 mL normal saline and injected by 11 sub urothelial injections
Other Names:
  • Vitagen Inj., Taiwan Biotech Co., Ltd., Taipei, Taiwan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary Voiding Symptoms Analysis
Time Frame: 3 days
Patients were asked to provide a three-day voiding frequency volume chart prior the treatment to record episodes of urinary voiding symptoms including urinary frequency, urgency, and nocturia.
3 days
Global Response Assessment (GRA)
Time Frame: Up to 7 months
GRA examined the overall response to treatment. Patients were requested to rate symptoms on a seven-point centered scale from markedly-, moderately-, and slightly- worse, no change, slightly-, moderately-, and markedly-improved.
Up to 7 months
International Prostate Symptom Score (IPSS)
Time Frame: Up to 7 months

The severity of voiding symptoms was evaluated by using the International Prostate Symptom Score (IPSS-TOTAL), and the IPSS-voiding (IPSS-V) and IPSS-storage (IPSS-S) sub-scores were also recorded. There were 7 questions including questions of IPSS-V and IPSS-S.

The IPSS-V is the sum of the answers to question 1 (incomplete emptying), question 3 (intermittency), question 5 (weak stream), and question 6 (straining to void). Oppositely, the IPSS-S is the sum of the answers to question 2 (frequency), question 4 (urgency), and question 7 (nocturia). The IPSS subscore can be used to evaluate symptom severity or the results of treatment.

IPSS-TOTAL then took into account the total score from the answers of the questions that can therefore range from 0 to 35 (0-7 mild symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic).
Up to 7 months
Visual Analogue Scale (VAS)
Time Frame: Up to 7 months
VAS is a pain rating scale which its scores are based on patient self-assessment measures of symptoms that are recorded with a single handwritten mark placed at one point of 10-point along the length of a 10-cm line. The line represents the pain condition, the left end of line scale (0 cm) represents "no pain" and the right end of the scale (10 cm) shows the "worst pain".
Up to 7 months
O'Leary-Sant Score (OSS)
Time Frame: Up to 7 months

OSS indexes have eight questions assessing pain and voiding symptoms. OSS is obtained from O'Leary Sant instrument which evaluates a Symptom Index (ICSI with range: 0-20 points) and a Problem Index (ICPI with range: 0-16 points), each of which contains four questions related to urinary and pain symptoms. For each index, the score is calculated by summing the points for each item. A maximal index score of 36 reflects maximal symptom and problem severity.

The Symptom Index covers various areas, including whether the patient feels the need to urinate with little or no warning, has to urinate more frequently than every 2 hours, needs to get up during the night to urinate, and has pain in the bladder. The Problem Index evaluates other aspects, such as urinary frequency during the day, the urinary frequency at night, the need to urinate with little or no warning, and burning, pain, discomfort, or pressure on the bladder. Both indices evaluate the situation over the previous month.
Up to 7 months
5-Item Brief Symptom Rating Scale (BSRS-5)
Time Frame: Up to 7 months
BSRS-5 evaluated the quality of life of patients. It contained five items of a self-administered questionnaire that is derived from the 50-item brief symptom rating scale. The score for each item ranges from 0 to 4 (from not at all to extremely). A total score on the BSRS-5 above 14, between 10 and 14, and between 6 and 9 indicated severe, moderate, and mild symptoms, respectively.
Up to 7 months
5-item Female Sexual Function Index (FSFI-5)
Time Frame: Up to 7 months
FSFI-5 was performed to assess the sexual dysfunction possibility of female patients. FSFI-5 contained item-by-item combinations of the 5 domains of sexual "desire", "arousal", "lubrication", "orgasm", and "satisfaction". The 5 items were derived from 19 items of FSFI questionnaire.
Up to 7 months
Luminex Assay of Growth Factors
Time Frame: Up to 7 months
Urine samples were collected and stored at 4°C until analysis. Samples were analyzed for the presences of 4 analytes: epidermal growth factor (EGF), hepatocyte growth factor (HGF), placental growth factor-1 (PIGF-1), and vascular endothelial growth factor-D (VEGF-D). Their concentration was measured using a Growth Factor 11-Plex Human ProcartaPlex™ Panel assay kit with magnetic beads (EPX110-12170-901, Thermo Fisher Scientific, MA, USA) and examined with an automated immunoassay analyzer (Luminex™ 100 IS System, Luminex, TX, USA) and the accompanying ProcartaPlex Analyst Software 1.0 (Thermo Fisher Scientific, MA, USA) according to the manufacturer's instructions.
Up to 7 months
Luminex Assay of Cytokine Assay
Time Frame: Up to 7 months
The levels of serum cytokines [interleukin-6 (IL-6), IL-10, IL-12p70, IL-13, IL-17F, and IL-27] in blood samples were detected using a magnetic bead-based multiplex immunoassay MILLIPLEX MAP Human Th17 Magnetic Bead Panel (Merck KGaA, Darmstadt, Germany) according to the manufacturer's protocol. The MAGPIX® System reader was used to acquire the data of cytokines, which was output as concentration (pg/mL) using the Belysa™ Immunoassay Curve Fitting Software (Merck KGaA, Darmstadt, Germany).
Up to 7 months
Statistics Analysis
Time Frame: Up to 7 months
Urinary voiding symptoms analysis, the score of questionnaires (GRA, IPSS-TOTAL, IPSS-V, IPSS-S, VAS, ICSI, ICPI, BSRS5, and FSFI5), Luminex assay result of growth factors and cytokines assay were compared between and after treatment. Results are presented as mean values plus or minus standard deviations. Statistical comparisons between the groups were tested using a chi-square test for categorical variables, and an independent t test or a Wilcoxon test for nonparametric data was used for multiple comparisons. The correlation analysis and coefficient statistical method were performed for comparing VAS questionnaire and growth factor relation. A P value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS 18.0 statistical software (SPSS Inc., IL, USA).
Up to 7 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Defense Medical Center, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Actual)

September 11, 2020

Study Completion (Actual)

October 11, 2020

Study Registration Dates

First Submitted

March 25, 2021

First Submitted That Met QC Criteria

March 25, 2021

First Posted (Actual)

March 30, 2021

Study Record Updates

Last Update Posted (Actual)

April 5, 2021

Last Update Submitted That Met QC Criteria

April 1, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DEXTROSE2019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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