Platelet-Rich Plasma (PRP) Injection in Treatment of Interstitial Cystitis

Intravesical Injections of Platelet-Rich Plasma (PRP) in Treatment of Interstitial Cystitis Refractory to Conventional Treatment - A Prospective, Clinical Trial

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic disease of unknown etiology characterized by urgency frequency and suprapubic pain at full bladder. Current treatments are usually unsuccessful in completely eradicating bladder pain and increasing bladder capacity. Autologous platelet-rich plasma (PRP) is growing in popularity as a therapy to augment wound healing, speed the recovery from muscle and joint injuries, and enhance recovery after surgical repair. PRP is extremely rich in growth factors and cytokines, which regulate tissue reconstruction and has been studied extensively among trauma patients and trauma experimental models. Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells and PRP. This clinical trial attempts to use autologous PRP in treatment of interstitial cystitis refractory to currently available medical treatment or intravesical therapy. The results of this study might provide clinical evidence for a novel therapeutic regimen in the treatment of IC/PBS.

Study Overview

• Status: Unknown
• Conditions: Interstitial Cystitis
• Intervention / Treatment: Biological: Platelet-Rich Plasma

Detailed Description

Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a debilitating chronic disease of unknown etiology characterized by urgency frequency and suprapubic pain at full bladder. Current treatments are usually unsuccessful in completely eradicating bladder pain and increasing bladder capacity. Autologous platelet-rich plasma (PRP) is growing in popularity as a therapy to augment wound healing, speed the recovery from muscle and joint injuries, and enhance recovery after surgical repair. PRP is extremely rich in growth factors and cytokines, which regulate tissue reconstruction and has been studied extensively among trauma patients and trauma experimental models. Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells and PRP.

Aim: This clinical trial attempts to use autologous PRP in treatment of interstitial cystitis refractory to currently available medical treatment or intravesical therapy. The results of this study might provide clinical evidence for a novel therapeutic regimen in the treatment of IC/PBS.

Setting: Department of Urology, Buddhist Tzu Chi General Hospital.

Materials and Methods: A total of 30 patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled in this study. A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention. All patients have been treated with at least two types of treatment modalities including oral PPS, intravesical instillation of heparin, hyaluronic acid, or tricyclic antidepressant for at least 6 months but the symptoms remained unchanged or relapsed. All patients should have IC symptoms for at least 6 months, and proven to have grade 1 diffused glomerulations after cystoscopic hydrodistention (HD) within recent 1 year without Hunner's lesion. Eligible patients will be admitted for the treatment. The patients will receive intravesical injection of 12ml PRP (extracted from 50ml of patient's own whole blood) followed by cystoscopic hydrodistention under intravenous general anesthesia in the operation room. The procedure will repeat every one month for a total of four treatments. Blood (10ml) and urine samples (30ml) will be collected before intravesical PRP injection and at 4, 12 and 24 weeks after PRP injection.

Assessment: Primary end-point is the change of the O'Leary-Sant symptom score (including ICSI and ICPI) from baseline to 6 months after the first treatment day. Secondary endpoints include VAS, daily frequency, nocturia and FBC as record in 3-day voiding diary, Qmax, vided volume, PVR and global response assessment (GRA). Four visits are required at baseline screening (before first treatment) (V1), 1 month after the first treatment (V2, primary end-point), 4 weeks after the fourth treatment (V3), 24 weeks after the first treatment (V4, secondary end-point).

Urine samples will be collected at each time-point for NGF and cytokines tests. Bladder biopsy will be performed at baseline and 6 months after the first treatment day if possible.

Adverse events including UTI, AUR, large PVR (>150ml), dysuria and micturition pain will be recorded

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Hualien, Taiwan, 970
    • Buddhist Tzu Chi General Hospital

Participation Criteria

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. Adults with age of 20 years old or above
2. Patients with symptoms of frequency, urgency, nocturia, and/or bladder pain.
3. Proven to have glomerulations (at least grade 2) by cystoscopic hydrodistention under anesthesia in recent 1 year
4. Free of active urinary tract infection
5. Free of bladder outlet obstruction on enrolment
6. Free of overt neurogenic bladder dysfunction and limitation of ambulation
7. Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

1. Hunner's lesion proven by cystoscopy
2. Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
3. Patients with bladder outlet obstruction on enrollment
4. Patients with postvoid residual >250ml
5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
6. Patients have laboratory abnormalities at screening including: ALT> 3 x upper limit of normal range, AST> 3 x upper limit of normal range; Patients have abnormal serum creatinine level > 2 x upper limit of normal range
7. Patients with any contraindication to be urethral catheterization during treatment
8. Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
9. Patients with any other serious disease considered by the investigator not in the condition to enter the trial
10. Patient had received intravesical onabotulinumtoxinA treatment for IC within recent 3 months
11. Patients participated investigational drug trial within 1 month before entering this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Platelet-rich plasma treatment arm; Patients who meet all eligible requirements for entry into the study will be treated with intravesical injection of PRP (extracted from 50ml whole blood ) at 20 sites	Biological: Platelet-Rich Plasma; Patients who meet all eligible requirements for entry into the study will be treated with intravesical injection of PRP (extracted from 50ml whole blood ) at 20 sites; Other Names: PRP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
O'Leary-Sant Symptom Score	1. Change of the O'Leary-Sant symptom score (including IC symptom index, ICSI, and IC problem index, ICPI)	from baseline to 1 month after the first treatment day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analog score (VAS) for pain	Net change of the Visual analog score (VAS) for pain (from 0 to 10)	from baseline to 6 months after the treatment day
Functional bladder capacity (FBC)	Net change of functional bladder capacity	from baseline to 6 months after the treatment day
Voiding frequency	Net change of voiding frequency at daytime and voiding frequency at night time as record in 3-day voiding diary	from baseline to 6 months after the treatment day

Collaborators and Investigators

• Sponsor: Buddhist Tzu Chi General Hospital
• Investigators: Principal Investigator: Hann-Chorng kuo, M.D, Department of Urology, Buddhist TzuChi General Hospital

Publications and helpful links

General Publications

• Jiang YH, Kuo YC, Jhang JF, Lee CL, Hsu YH, Ho HC, Kuo HC. Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis. Sci Rep. 2020 Sep 16;10(1):15218. doi: 10.1038/s41598-020-72292-0.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2017
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: April 3, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: intersitial cystitis; Bladder pain syndrome; Intravesical treatment
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis; Cystitis, Interstitial
• Other Study ID Numbers: TCGH10548A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share data with other researchers

Drug and device information, study documents

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