title: Daily intravesical instillation of 1 mg nociceptin/orphanin FQ for the control of neurogenic detrusor overactivity: a multicenter, placebo controlled, randomized exploratory study.
abstract: OBJECTIVE
  We studied the feasibility, safety and efficacy of daily intravesical instillation of 1 mg of the endogenous peptide nociceptin/orphanin FQ in a selected group of patients who perform clean intermittent self-catheterization for neurogenic detrusor overactivity incontinence.
  
  
  METHODS
  A total of 18 patients with neurogenic detrusor overactivity incontinence and on clean intermittent self-catheterization were prospectively randomized to receive 1 mg nociceptin/orphanin FQ in 10 cc saline (9) or placebo (saline) solution (9) at the first morning catheterization for 10 days. All patients completed a voiding diary using a frequency/volume chart according to International Continence Society guidelines, and reported daily incontinence frequency. Mean changes in incontinence episode frequency and voiding diary mean bladder capacity from baseline throughout treatment were the primary outcome variables. Urodynamic parameters (cystomanometric bladder capacity, maximum bladder pressure) were also recorded at baseline and during the study.
  
  
  RESULTS
  The 2 groups were well balanced and all patients completed the study. The urodynamic parameters recorded during the study showed an increase in cystomanometric bladder capacity and a decrease in maximum bladder pressure compared to baseline only in patients assigned to the nociceptin/orphanin FQ group. Mean daily urine leakage episodes during nociceptin/orphanin FQ treatment were 0.94 vs a pretreatment baseline of 2.18 (p < 0.05), while no significant changes were reported in the placebo group (2.06 vs 2.43 baseline). The total mean voiding diary bladder capacity increased from 171 +/- 70 to 294 +/- 107 ml in patients receiving nociceptin/orphanin FQ, while voiding diary mean bladder capacity remained unchanged in patients receiving placebo (from 182 +/- 55 to 178 +/- 23 ml). No significant problems related to feasibility of the procedure as well as significant side effects were reported by patients.
  
  
  CONCLUSIONS
  This study showed that intravesical nociceptin/orphanin FQ but not placebo inhibited the micturition reflex in patients with neurogenic detrusor overactivity incontinence, and demonstrated the clinical efficacy of nociceptin/orphanin FQ during 10 days of treatment. These findings support the use of nociceptin/orphanin FQ peptide receptor agonists as an innovative therapeutic approach for controlling detrusor overactivity incontinence.
authors.affiliation: Department of Urology, Casa di Cura Santa Chiara Firenze, GIOMI Group, Florence, Italy. lazzeri.m@tiscali.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.forename: Michele
authors.initials: M
authors.lastname: Spinelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Malaguti
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Patrizia
authors.initials: P
authors.lastname: Beneforti
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.forename: Damiano
authors.initials: D
authors.lastname: Turini
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018847:Opioid Peptides / Q000008:administration & dosage*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D000097629:Nociceptin