Medication Effects on Periurethral Sensation,Urethral Sphincter Activity and Pressure Flow Parameters

Women without urinary incontinence or bladder symptoms (healthy controls)will undergo urethral testing prior to randomization to one of 5 medications or placebo. Participants will take an oral medication for 2 weeks and then return for repeat testing.

• Pseudoephedrine (Drug): Pseudoephedrine ER 120 mg by mouth once daily for 2 weeks
• Tamsulosin (Drug), also known as Flomax: Tamsulosin 0.4mg by mouth daily for 2 weeks
• Imipramine (Drug), also known as Tofranil: Imipramine 25mg daily by mouth for 2 weeks
• Cyclobenzaprine (Drug), also known as Flexeril: Cyclobenzaprine 10mg daily by mouth for 2 weeks
• Lactose capsule (Drug): Lactose capsule 1 by mouth daily for 2 weeks
• Solifenacin (Drug), also known as VESIcare: Solifenacin 5mg by mouth daily for 2 weeks

Primary outcomes

• Difference (Pre - Post) in Amplitude (Microvolts) of Urethral Sphincter Activity as Measured by Quantitative Concentric Needle EMG [2 weeks]: Concentric needle EMG was used to measure urethral sphincter activity at 2-3 sites around the urethral meatus before and after 2 weeks of therapy with one of 6 randomly assigned medications. Two methods of quantitative electromyography were performed on all subjects. (1) Multi-Motor Unit Action Potential (MUP) analysis, which has been shown to be the most sensitive technique in distinguishing neuropathic from control muscles; and (2) interference pattern analysis (IPA) which reflects changes in MUP recruitment from weak effort to maximal contraction.

Other outcomes

• Difference (Pre - Post) in Urethral Sensation (Milliamps) as Measured by Current Perception Threshold Testing. [2 weeks]: Current Perception Threshold testing was used to measure urethral sensation before and after 2 weeks of therapy with one of 6 randomly assigned medications. We performed CPT testing in the urethra using a Neurometer®, which is a constant current stimulator capable of delivering sine wave electrical stimuli at 3 frequencies (2000 Hz, 250 Hz and 5 Hz). At all 3 frequencies, the stimulus intensity was gradually increased until first perceived, and then decreased until no longer perceptible. CPT values were obtained using a semi-automated forced choice paradigm.
• Difference (Pre - Post) in Maximum Urine Flow Rate (Qmax) (Milliliters Per Second) as Measured by Pressure Flowmetry [2 weeks]: Pressure Flowmetry was used to measure maximum urine flow rate (Qmax)before and after 2 weeks of therapy with one of 6 randomly assigned medications. A 300 cc bladder fill was performed through the catheter, the catheter was removed, and transurethral and transrectal pressure transducers were placed for the pressure flow study. Voiding was performed in the seated position. Information obtained for the database included Qmax, average flow rate, time to Qmax, detrusor pressure at maximum flow rate, voided volume, and a calculated post-void residual.

Sex: Female, ages: 19 Years to 51 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy Females only
* Ages 19-51 and up including pre-menopausal older women who have had a normal menstrual cycle for the prior 3 months
* Able to take oral medication for 2 weeks
* For women of child bearing potential,willing to use an approved method of birth control during the study

Exclusion Criteria:

* Urinary Incontinence or other bladder symptoms
* Known neurologic disease that may impair urethral tone or sensation
* Currently taking a class of medication that is being tested (alpha-antagonists, anticholinergics, sympathomimetics, tricyclic antidepressants, or skeletal muscle relaxants)
* History of QTc prolongation or cardiac arrhythmia
* Pregnant, breastfeeding, or are less than 6 months postpartum
* Known hypersensitivity to or other contraindications to taking any of the study medications

Participant flow

Outcome results

• Difference (Pre - Post) in Amplitude (Microvolts) of Urethral Sphincter Activity as Measured by Quantitative Concentric Needle EMG (Primary), Median, microvolts: Pseudoephedrine 120mg ER Daily -18 (-108 to 89); Solifenacin 5mg Daily 10 (-56 to 60); Tamsulosin 0.4mg Daily 11 (-102 to 52); Imipramine 25mg Daily -15 (-157 to 75); Cyclobenzaprine 10mg Daily 12 (-71 to 104); Lactose Capsules, One Daily 36 (23 to 45) (p >0.05)
• Difference (Pre - Post) in Urethral Sensation (Milliamps) as Measured by Current Perception Threshold Testing. (Other pre specified), Median, Milliamps: Pseudoephedrine 120mg ER Daily 0.06 (0.0 to 0.68); Solifenacin 5mg Daily 0.06 (-0.01 to 0.34); Tamsulosin 0.4mg Daily -0.8 (-0.8 to 0.04); Imipramine 25mg Daily -0.12 (-0.4 to 0.12); Cyclobenzaprine 10mg Daily 0.0 (-0.16 to 0.28); Lactose Capsules, One Daily 0.03 (-0.03 to 0.05) (p >0.05)
• Difference (Pre - Post) in Maximum Urine Flow Rate (Qmax) (Milliliters Per Second) as Measured by Pressure Flowmetry (Other pre specified), Median, milliliters per second: Pseudoephedrine 120mg ER Daily -7.3 (-23.8 to 7.2); Solifenacin 5mg Daily 5.0 (-24.5 to 21.4); Tamsulosin 0.4mg Daily -5.6 (-45.3 to 16.5); Imipramine 25mg Daily -6.6 (-55.1 to 8.7); Cyclobenzaprine 10mg Daily 10.3 (-30.1 to 31.9); Lactose Capsules, One Daily 10.4 (-27.6 to 22.8)

Adverse events

Time frame: Adverse Event data were collected from 5/27/10, the date of first participant enrolled, until 9/20/10 when the last participant completed the study.

Other adverse events by term

• Results publication: Greer WJ; Gleason J; Szychowski JM; Goode P; Kenton K; Richter HE. Medication Effects on Urethral Current Perception Thresholds and Pressure Flow Parameters. Fem Pelv Med Recons Surg 2011;17:S33.

• Holly E Richter, PhD, MD, Principal investigator, University of Alabama at Birmingham