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

Study Overview
=================
Brief Summary
-----------------
Lower urinary tract symptoms such as urinary leakage and overactive bladder affect millions of American women. Women may develop these problems because the innervation of the muscles of the bladder and urethra are injured. Most research on treating these problems has focused on the abnormalities of the bladder muscle, but newer studies have shown abnormalities in the innervation and muscle function of the urethra. Women with these symptoms may benefit from treatment with medications to improve their urethral function. However, to truly understand what types of medications will help women with these symptoms, the investigators wish to study how these medications affect innervation and muscle function in healthy women who do not have lower urinary tract symptoms.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Urethral Sphincter Activity

Intervention / Treatment
-----------------
* Drug: Pseudoephedrine
* Drug: Tamsulosin
* Drug: Imipramine
* Drug: Cyclobenzaprine
* Drug: Lactose capsule
* Drug: Solifenacin


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 51 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pseudoephedrine<br>Pseudoephedrine 120mg extended release tablets | Drug: Pseudoephedrine<br>* Pseudoephedrine ER 120 mg by mouth once daily for 2 weeks<br>|
| Active Comparator: Solifenacin<br>Solifenacin 5mg capsule | Drug: Solifenacin<br>* Solifenacin 5mg by mouth daily for 2 weeks<br>* Other names: VESIcare;|
| Active Comparator: Tamsulosin<br>Tamsulosin 0.4mg capsule | Drug: Tamsulosin<br>* Tamsulosin 0.4mg by mouth daily for 2 weeks<br>* Other names: Flomax;|
| Active Comparator: Imipramine<br>Imipramine 25mg tablet | Drug: Imipramine<br>* Imipramine 25mg daily by mouth for 2 weeks<br>* Other names: Tofranil;|
| Active Comparator: Cyclobenzaprine<br>Cyclobenzaprine 10mg tablet | Drug: Cyclobenzaprine<br>* Cyclobenzaprine 10mg daily by mouth for 2 weeks<br>* Other names: Flexeril;|
| Placebo Comparator: Lactose capsules<br>Sham | Drug: Lactose capsule<br>* Lactose capsule 1 by mouth daily for 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference (Pre - Post) in Amplitude (Microvolts) of Urethral Sphincter Activity as Measured by Quantitative Concentric Needle EMG | 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. | 2 weeks |