Hypothesis / aims of study
Underactive bladder (UAB) is a disease of unmet medical need that affects over 15% of the population, yet no consensus treatment exists beside clean intermittent catheterization (CIC). We hereby report on the first regulatory approved clinical trial of a one-year prospective open label physician-initiated study assessing the safety and efficacy of intradetrusor injected autologous muscle-derived cells (AMDC) treatment for UAB.
Study design, materials and methods
20 non-neurogenic UAB patients were treated and all patients had at least a 1 month visit post-injection. Baseline evaluation included medical history, physical examination, 3-day voiding diary, multi-channel urodynamic testing, and endoscopy to confirm no obstruction. Approximately 150 mg of quadriceps femoris muscle was collected using a spirotome 8-gauge needle. The muscles biopsy was sent to Cook MyoSite (Pittsburgh, PA) for processing. Upon reaching a final concentration of 62.5 million AMDC/mL, patients received 30 intradetrusor injections of 0.5 mL delivered to the bladder, for a total of 15 mL, performed utilizing a flexible cystoscope under direct vision using topical local anesthesia. Follow-up assessments included adverse events and efficacy via voiding diary and urodynamics testing at 1, 3, 6 & 12-month post-injection. An optional second injection was offered at the end of the 6 months visit.
Results
20 patients received the first injection and 19 of 20 patients requested and received a second injection. Age of patients ranged from 41-82 years old with a median age of 65 years. There were 16 male (80%) and 4 female (20%) patients. Etiology included seven men (35%) with persistent urinary retention after transurethral resection of the prostate for benign prostatic hyperplasia and 13 patients (65%) with idiopathic chronic urinary retention. At baseline, 10/20 (50%) patients were CIC dependent, 9/20 patients reported mixed voiding, and 1/20 (5%) patients reported no CIC, but had persistent high post-void residual (PVR) urine volume. 1 patient dropped from this study before the 12-month follow-up assessment.
Table 1 is the patient-reported global response assessment (GRA). At the primary outcome time point of 12 months, 11/19 patients (58%) reported a GRA > 5, showing slight to marked improvement in their UAB symptoms, compared to 6/20 (30%) patients at 3-months post-injection. One patient reported temporary worsening at month 6 but reported no change in symptoms from baseline at month 12.
Figure 1 illustrate the improvements in voiding efficiency from baseline to 6- and 12-months post injection in patients who were able to void during the urodynamics test at the 6- and 12-mont follow-up visits.
No serious procedure or treatment-related adverse events occurred. No adverse events related to the AMDC injection were reported. All biopsy and injection-related adverse events were expected complications and were either self-resolved or easily treated.
Interpretation of results
Analysis up to 12 months revealed encouraging improvement in bladder function and safety for UAB patients with catheter dependent chronic urinary retention who received intradetrusor AMDC injections. Improvements are noted in decreased patient PVR, increased voiding efficiency, and decreased catheter use. Limitations of study include small size and lack of randomization, but this is in line with a first in human physician-initiated feasibility study of safety and efficacy.