2008projectindex075Ogunnaike

Medical Student Research Fellowship for Summer 2008

Mentor: Babatunde Ogunnaike, MD
Department: Anesthesiology & Pain Management
Room number: PMH 2nd Floor
Mail Code: 9068
Phone number: 214-590-8536
E-mail: babatunde.ogunnaike@utsouthwestern.edu

Project # 1

Project title: A MULTICENTER, DOUBLE-BLIND RANDOMIZED, PLACEBO CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF PREGABALIN IN THE TREATMENT OF SUBJECTS WITH POST-OPERATIVE PAIN FOLLOWING TOTAL KNEE ARTHROPLASTY (TKA)

Human subjects IRB approved project number (where applicable): 032007-019

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Patient-based Research

Brief Description of Project: This study will compare the effects of oral pregabalin with placebo on postoperative pain after Total Knee Arthroplasty.

Pregabalin is an anticonvulsant agent approved by the United States Food and Drug Administration (FDA) for the treatment of neuropathic pain associated with post-herpetic neuralgia and diabetic neuropathy.
Fifty patients between 18 and 80 years of age will be recruited to participate in the study. Those with known allergy to pregabalin and those with a history of alcohol abuse, chronic pain, history of daily intake of analgesics or steroids, and patients with a history of malignancy, inflammatory arthritides, Lyme disease, fibromyalgia, neurological disorder will be excluded from the study. Blood tests will be performed before surgery to determine if a patient qualifies for enrollment in the study. A pregnancy test will also be performed to exclude pregnant women from the study. About 20 to 30 ml of blood will be collected for the tests.

This is a multicenter Phase III, randomized, double-blind, placebo controlled, parallel study, which will compare the efficacy, safety and tolerability of pregabalin in treating pain in subjects undergoing elective total knee arthroplasty (TKA). The study will be conducted in the US and the study population will include approximately 300 subjects undergoing elective TKA under regional anesthesia (i.e. epidural/spinal/peripheral nerve block). Approximately 100 subjects will be assigned to each of the three treatment groups and will receive a fixed dose of Pregabalin 150 mg/day (75 mg bid), Pregabalin 300 mg/day (150 mg bid) or matching placebo. All treatments will be initiated pre-operatively with 2 single doses at approximately 12 and 2 hours pre-surgery (75 mg, 150 mg and placebo, respectively) and continue twice a day for up to 6 weeks post-surgery. Rescue medication during all study phases (washout, hospital stay, post hospital discharge)
and up to visit 6 will consist of Vicodin® (hydrocodone bitartrate 5 mg/acetaminophen 500 mg), Percocet® (oxycodone hydrochloride/acetaminophen), or acetaminophen given prn up to the maximal recommended dose. Subjects will be assigned to receive their allocated treatment according to a computer generated randomization prepared prior to the start of the study. The study duration will be approximately 6 months: 1-2 week screening, a baseline visit 1-2 weeks prior to surgery, 2 to 6 weeks of post-operative dosing period including 3-5 days post
operative hospitalization and a 1-week taper. Post discharge, site visits will occur on post-op weeks 2, 4, 6 and 7 (post taper) and phone call follow-up will be done at 3 and 6 months. The trial will start with a 1-2 week screening phase during which baseline pain, sleep and anxiety assessments will be made and subjects trained on the use of the daily diary. Subjects will also be washed out of any prohibited medication, including NSAIDs and COX-2 selective inhibitors. Subjects will then be randomized to either pregabalin or placebo (baseline visit) and sent home with the pre-operative study medication. Oral treatment with pregabalin (75 mg or 150 mg) or placebo will be taken at bedtime the night before surgery and the day of surgery (2 hours prior to surgery). Each subject will be called the day prior to the day of surgery to be reminded to take his/her evening dose of pre-operative study medication and to complete the anxiety visual analogue scale (VAS-Anxiety). A second preoperative dose will be administered at the hospital approximately 2 hours prior to surgery. Subjects randomized to pregabalin will then receive 150 or 300 mg/day (i.e. 75 mg bid or 150 mg bid) for 2 to 6 weeks post-surgery, those randomized to placebo will receive placebo bid for the same duration. The duration of the post-operative dosing after hospital discharge will be determined by the subject's level of pain assessed at visits 4 (week 2) and 5 (week 4). Dosing of study medication will continue until visit 6 (week 6) unless mean worst pain is rated as ? 3 on the 11-point NRS at visit 4 or 5. Study medication will then be tapered over one week.

The study duration will be approximately 6 months:
· 1-2 week screening,
· a baseline visit 1-2 weeks prior to surgery,
· 2 to 6 weeks of post-operative dosing period including 3-5 days post operative hospitalization
· 1-week taper.
· Post discharge, site visits will occur on post-op weeks 2, 4, 6 and 7 (post taper) and phone call follow-up will be done at 3 and 6 months.
Medical students' role:
1. Assist physicians and study coordinator with patient recruitment - including history and physical examination, medical history review and patient consent
2. Operating room attendance for patient monitoring and data collection
3. Patient follow up both in-hospital and telephone follow up
4. Data collation and analysis

Project # 2

Project title: A Randomized, Double-Blind Multi-Center Dose-Ranging Study of the Efficacy and Safety of Pregabalin Compared To Placebo in the Adjunctive Treatment of Post-Surgical Pain after Primary Inguinal Hernia Repair

Human subjects IRB approved project number (where applicable): 112007-012

Animal subjects IRB approved project number (where applicable):

Brief Description of Project: This is a multi-center, multiple-dose, randomized, double blind, 4 arm, placebo controlled, parallel group study involving approximately 400 subjects eligible for the efficacy analysis with pain following unilateral open mesh, Lichtenstein inguinal herniorraphy, with general anesthesia.
The study is designed to assess the effect of pregabalin, two preoperative doses of 25 mg and 25 mg BID postoperatively, two preoperative doses of 75 mg and 75 mg BID postoperatively, and one preoperative dose of 75 mg and one preoperative dose of 150 mg and 150 mg bid postoperatively, compared to matched placebo on pain experienced and rescue medication use by subjects following open mesh procedure unilateral elective inguinal herniorraphy.
There is a second optional part of the study; the subject can still participate in the main study even if he/she is not willing to participate in this one. This second optional part of the study is being done to collect, store, and use subject's blood sample(s) to study genes, RNA, and proteins. The sample(s) and data obtained from the testing of these sample(s) will be examined only in relation to:
" response to the study drugs in the main drug study
" post-operative pain after inguinal hernia repair and related conditions
The study will be conducted with approximately 15-20 sites in approximately 5 countries. It is anticipated that approximately 600 subjects will be screened for the study to enroll approximately 400 subjects who meet all the selection criteria.
Subjects who are scheduled for inguinal herniorraphy under general anesthesia and who meet all the inclusion and no exclusion criteria are eligible to enter this study.

Medical students' role:
1. Assist physicians and study coordinator with patient recruitment - including history and physical examination, medical history review and patient consent
2. Operating room attendance for patient monitoring and data collection
3. Patient follow up both in-hospital and telephone follow up
4. Data collation and analysis

Project # 3

Project title: A Study Evaluating the Ability of the T-Line Tensymeter Blood Pressure Monitoring System to Predict Hemodynamic Instability Compared with Intermittent Sphygmomanometry (cuff method) in Geriatric Patients

Human subjects IRB approved project number (where applicable): 092006-028

Animal subjects IRB approved project number (where applicable):

Brief Description of Project: The T-line tensymeter is a new device to measure blood pressure. Data will be collected and compared to determine the accuracy of the device. Data collected during surgery will be the only accountability of activation in this study. There will be no deviation from standard of care; the T-line is an additional monitor.

The device will only be used according to label, and a synopsis of its details and approved usage follows:

" Trial Device: The trial device (T-line Tensymeter) is a FDA-cleared, Class II non-invasive continuous blood pressure measurement system that provides signals from which systolic, diastolic, and mean blood pressure is derived through the use of a transducer system placed on the wrist. The trial device consists of five (5) separable sub-systems, identified as follows:

1. A proprietary pressure transducer assembly
2. A multiple-use wrist-restraint and/or actuator attachment device
3. A sensor alignment and positioning device (the actuator)
4. An interface electronics module which provides the controls to the actuator and connects to the existing, user (hospital or provider) supplied patient monitor via the invasive blood pressure port
5. An isolated power supply

" Trial objectives:

1. To assess the direct statistical comparison of the T-line blood pressures to the cuff control
2. To monitor adverse device effects and the resultant effects of continuous pressure application to the dermis