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

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

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.

Study Overview

• Status: Completed
• Conditions: Urethral Sphincter Activity
• Intervention / Treatment: Drug: Pseudoephedrine; Drug: Solifenacin; Drug: Tamsulosin; Drug: Imipramine; Drug: Cyclobenzaprine; Drug: Lactose capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham, The Kirklin Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 51 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pseudoephedrine; Pseudoephedrine 120mg extended release tablets	Drug: Pseudoephedrine; Pseudoephedrine ER 120 mg by mouth once daily for 2 weeks
ACTIVE_COMPARATOR: Solifenacin; Solifenacin 5mg capsule	Drug: Solifenacin; Solifenacin 5mg by mouth daily for 2 weeks; Other Names: VESIcare
ACTIVE_COMPARATOR: Tamsulosin; Tamsulosin 0.4mg capsule	Drug: Tamsulosin; Tamsulosin 0.4mg by mouth daily for 2 weeks; Other Names: Flomax
ACTIVE_COMPARATOR: Imipramine; Imipramine 25mg tablet	Drug: Imipramine; Imipramine 25mg daily by mouth for 2 weeks; Other Names: Tofranil
ACTIVE_COMPARATOR: Cyclobenzaprine; Cyclobenzaprine 10mg tablet	Drug: Cyclobenzaprine; Cyclobenzaprine 10mg daily by mouth for 2 weeks; Other Names: Flexeril
PLACEBO_COMPARATOR: Lactose capsules; Sham	Drug: Lactose capsule; Lactose capsule 1 by mouth daily for 2 weeks

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference (Pre - Post) in Urethral Sensation (Milliamps) as Measured by Current Perception Threshold Testing.	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.	2 weeks
Difference (Pre - Post) in Maximum Urine Flow Rate (Qmax) (Milliliters Per Second) as Measured by Pressure Flowmetry	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.	2 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Astellas Pharma Inc

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: December 7, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (ESTIMATE): December 9, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 8, 2012
• Last Update Submitted That Met QC Criteria: June 1, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Neuromuscular Agents; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Vasoconstrictor Agents; Muscle Relaxants, Central; Nasal Decongestants; Tamsulosin; Ephedrine; Pseudoephedrine; Solifenacin Succinate; Cyclobenzaprine; Imipramine
• Other Study ID Numbers: VESI-9E03-UAB