4-aminopyridine Treatment for Nerve Injury

Study Overview
=================
Brief Summary
-----------------
To evaluate the role of 4-aminopyridine (4-AP) on the course of recovery after peripheral nerve traction and/or crush injury. This study aims to test the hypothesis that 4-aminopyridine speeds the often slow and unpredictable recovery after peripheral nerve traction and/or crush injuries.

Detailed Description
-----------------
To evaluate the role of 4-AP on the recovery of nerve function we will be giving patients with prostate cancer who are undergoing robot assisted radical prostatectomy (RP) either 4-AP or placebo in the perioperative period. This population of patients was selected as nerve crush injury during RP is thought to contribute to erectile dysfunction and urinary continence post operatively.

Official Title
-----------------
4-aminopyridine Treatment for Nerve Injury Resulting From Radical Retro-Pubic Prostatectomy

Conditions
-----------------
Nerve Injury, Prostate Cancer

Intervention / Treatment
-----------------
* Drug: 4-Aminopyridine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Male patients with organ-confined, non-metastatic prostate cancer (stages cT1c-T2c), planning to undergo Robotic-Assisted Laparoscopic Bilateral Nerve Sparing Radical Prostatectomy (NSRP) Prostate-Specific Antigen (PSA) levels less than 15 ng/ml (within the last 12 months), with biopsy-proven prostate cancer, for whom postoperative adjuvant therapy (e.g. radiation or androgen deprivation therapy) is not expected to be needed Ages 45-75 An Abridged International Index of Erectile Function-Erectile Function (IIEF-5) score of greater than or equal to 17 at time of screening Has experienced at least 6 months of regular sexual activity and sexual activity during the 12 weeks prior to prostate biopsy or surgery Willingness to abstain from treatments for Erectile Dysfunction until 3 months after surgery Willingness to participate and able to provide informed consent Exclusion Criteria Planned adjuvant therapy after NSRP based on specimen pathology and stage of prostate cancer (stage T3 or greater), positive lymph nodes or positive surgical margins Neo-adjuvant therapy prior to NSRP History of recurrent prostate cancer History of seizures, multiple sclerosis, stroke or any other diagnosed neurological disorder History of non-organ confined or metastatic prostate cancer (clinical Stages T3 or greater) History of known hypersensitivity to 4AP Patients with history of penile surgery other than circumcision or endoscopic urethral stricture surgery Renal impairment based on calculated GFR (GFR<60 mL/min) Use of any other aminopyridine medications for any other indication

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled trial of 4AP vs placebo for nerve injury
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Investigational Treatment<br>4-Aminopyridine (FDA-approved drug) Subjects will not take more than 2 tablets in a 24-hour period Subjects will take the tablets whole. They will not break, crush, chew, or dissolve tablets before swallowing. The subjects will be told that the medication is released slowly over time and if the tablet is broken, the medicine may be released too fast which can raise the chance of having a seizure. Study drug can be taken with or without food. If a dose is missed they should not make up the missed dose. They will be told not to take two doses at the same time but to take the next dose at the regular scheduled time. Subjects will be reminded not to take study drug together with other aminopyridine medications, including compounded 4-AP (sometimes called 4-aminopyridine or fampridine). | Drug: 4-Aminopyridine<br>* FDA-approved tablets.<br>* Other names: Fampridine;|
| Placebo Comparator: Group B: Placebo<br>Subjects will receive an oral dose of placebo treatment the day after surgery, continuing daily for 3 months (90 days) following the same administration instructions as the investigational treatment. The placebo tablets will be manufactured by The University of Iowa Pharmaceuticals, 115 South Grand Avenue G-20, Iowa City, IA 52242. The Investigational Drug Service at the University of Rochester will manage the placebos. Placebo composition will include: 97% Microcrystalline Cellulose, NF (Avicel Ph 102) 2% Sodium Starch Glycolate, NF 1% Magnesium Stearate, NF The placebo will be covered in White Opadry, formulation OY-S-9603 and tooled to look similar to the investigational treatment. | Other: Placebo<br>* Placebo will be tooled to look similar to the study drug.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Michigan Incontinence Sympton Index (M-ISI) (change over time) | Incontinence measurement (change over time) | Pre-operative visit, and every seven days (starting after surgery, i.e., 7 days post-op) for 6 months (up to 25 times). | 
| International Index of Erectile Function (IIEF) (change over time) | Erectile function measurement tool. (change over time) | Pre-operative visit, and every seven days (starting after surgery, i.e., 7 days post-op) for 6 months (up to 25 times). | 
| University of Rochester Placebo vs. Active Drug Questionnaire | Specific questions regarding patient blinding | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Diary | Subjects will record the time each day that they take the study drug/ placebo. | Daily for 90 days. | 
| University of Rochester Attempted Sexual Activity Questionnaire | Sexual activity assessment | Pre-operative visit, and every seven days (starting after surgery, i.e., 7 days post-op) for 6 months (up to 25 times). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prostatectomy, erectile dysfunction, prostate cancer, nerve injury, incontinence