4-aminopyridine Treatment for Nerve Injury

Sponsor

University of Rochester (Other)

Overall Status

Recruiting

CT.gov ID

NCT03701581

Collaborator

Milton S. Hershey Medical Center (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nerve Injury Prostate Cancer	Drug: 4-Aminopyridine Other: Placebo	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized placebo-controlled trial of 4AP vs placebo for nerve injuryRandomized placebo-controlled trial of 4AP vs placebo for nerve injury

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 5, 2021

Anticipated Primary Completion Date :

Aug 5, 2023

Anticipated Study Completion Date :

Aug 5, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Investigational Treatment 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 FDA-approved tablets. Other Names: 4-AP Fampridine
Placebo Comparator: Group B: Placebo 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 Placebo will be tooled to look similar to the study drug.

Arm

Intervention/Treatment

Experimental: Group A: Investigational Treatment

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

FDA-approved tablets.

Other Names:

4-AP

Fampridine

Placebo Comparator: Group B: Placebo

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

Placebo will be tooled to look similar to the study drug.

Outcome Measures

Primary Outcome Measures

Michigan Incontinence Sympton Index (M-ISI) (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).]
Incontinence measurement (change over time)
International Index of Erectile Function (IIEF) (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).]
Erectile function measurement tool. (change over time)
University of Rochester Placebo vs. Active Drug Questionnaire [through study completion, an average of 1 year]
Specific questions regarding patient blinding

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 75 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Rochester Department of Urology	Rochester	New York	United States	14642
2	University of Rochester Medical Center	Rochester	New York	United States	14642

Sponsors and Collaborators

University of Rochester
Milton S. Hershey Medical Center

Investigators

Principal Investigator: Ahmed Ghazi, MD, University of Rochester, Department of Urology
Study Director: John Elfar, MD, University of Rochester, and The Pennsylvania State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

John Elfar, Adjunct Associate Professor, Department of Orthopaedics (URMC) and Vice Chairman, Department of Orthopaedics and Rehabilitation (Penn State), University of Rochester

ClinicalTrials.gov Identifier:

NCT03701581

Other Study ID Numbers:

57379

First Posted:

Oct 10, 2018

Last Update Posted:

May 16, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by John Elfar, Adjunct Associate Professor, Department of Orthopaedics (URMC) and Vice Chairman, Department of Orthopaedics and Rehabilitation (Penn State), University of Rochester

Additional relevant MeSH terms:

Prostatic Neoplasms

Wounds and Injuries

4-Aminopyridine

Study Results

No Results Posted as of May 16, 2022