Office Use Only MGFY13 Okere Exceptional Merit Grants Program for Faculty and Staff Grant Application Cover Sheet Contact Information for the Primary Person submitting the Proposal: Name and Title: Arinze Nkemdirim Okere, PharmD, MS. Department: College of Pharmacy Address: 25 Michigan Street NE City/State/ZIP: Grand Rapids Phone Number: 616-391-0863 Email: [email protected] Project Name: Pilot Study: The Role of Alpha Lipoic Acid for the Treatment of Diabetic Retinopathy Purpose of the Grant Request for a supporting fund to study the role of alpha lipoic acid for the treatment of diabetic retinopathy Amount Requested: $5000 Total Project Cost: $19000 Dates of the Project: September 2013 Project Completion Date: December 2014 Approval and signatures: The Foundation Office will forward your application to the names you enter below. It will be your responsibility to follow up to ensure the proper signatures are obtained and the completed cover sheet is returned to the Foundation Office. Faculty -- Dean and Department Head Support. The project proposal in the attached document is consistent with the needs and direction of the department and college. Enter the name of your Dean and Department Head/Chair below. Dean: Dr. Stephen Durst Signature, Dean Department Head/Chair: Dr. Cambria Dehoag Signature, Department Head/Chair STAFF - Vice President and Supervisor support: The project proposal in the attached document is consistent with the needs and direction of the department and unit. Enter the name of your Vice President and Supervisor below. Vice President: Dr. Fritz J. Erickson Signature, Vice President Supervisor: Dr. Cambria Dehoag Signature, Supervisor Narrative: When completing the narrative portion, please contain discussion to the allowable space on the page. A statement of how the project demonstrates exceptional merit in advancing the mission of Ferris State University. Include how the project compliments and enhances other efforts on campus and how the project compliments and enhances other efforts on campus and how the project will continue in the future. One of the primary objectives of Ferris State University is to be involved in collaborative research activities across its campuses and beyond. This pilot study will be a collaboration between faculties in Ferris State University, College of Pharmacy (COP) and Michigan College of Optometry (MCO). It will enhance the research collaborative effort in this community. The study will provide a direction for a larger study. Upon successful completion of this pilot clinical study, the investigators will apply for NIH (National Institute of Health) funding to conduct a randomized study with a larger population sample. This will further enhance the collaboration effort between the two colleges (MCO and COP). Secondly, during the reaccreditation process for the College of Pharmacy there was a strong emphasis from the accreditation body that FSU College of Pharmacy should direct their effort toward research. The success of this study will be one way of meeting the college needs. Third, the execution of this study has the potential to expose Doctors of Pharmacy students and Optometry to areas of research. Interested students will actively be involved in research and students will be mentored by different investigators. This will provide the avenue to teach the students basic principles of research design and methodology. There is no better way to accomplish this than by mentoring students one on one in an ongoing research. This is an opportunity that has been rarely offered to FSU PharmD students. Clinical research is an area that students least think about. Again, through one on one mentoring, students will be able to take advantage of this opportunity. A brief description of the project being proposed and the desired outcomes (maximum 1 page). Objective: The proposed study will be a 12-month pilot study demonstrating the role of alpha lipoic acid in patients who have moderate nonproliferative diabetic retinopathy. The primary aim of this study is to test the hypothesis that the addition of alpha lipoic acid in a diabetic patient’s therapeutic regimen can decrease the progression of diabetic retinopathy and preserve visual acuity. Methods: This study is designed to be a 12-month double blinded randomized trial. Eligible patients will be randomized to control or intervention group. Study participants in the “treatment” assignment group will receive 600 mg oral administration of lipoic acid while control group will follow routine care alone (without lipoic acid). Rationale: Increased production of free radicals and depletion of antioxidants are commonly observed in diabetic patients. Based on animal studies, increased production of free radicals tends to persist even after blood glucose is tightly controlled. The rationale of using a potent antioxidant is based on the observation that increased oxidative stress associated with hyperglycemia can contribute to cellular injury leading to apoptosis; consequently, leading to diabetic retinopathy. Evidence from animal model showed that alpha lipoic acid (a potent antioxidant) was effective for decreasing the progression of diabetic retinopathy and in reducing free radicals. However, there is no randomized study that has investigated the use of alpha lipoic acid in the management of diabetic retinopathy. Human studies showing the beneficial effect of alpha lipoic acid has only been shown on diabetic patient with neuropathy. It is important to note that exaggerated production of reactive oxygen species (ROS) is related to progression of nerve dysfunction and is one of the primary causes of diabetic neuropathy. Therefore, we hypothesize that therapy that can exert a powerful antioxidant activity can provide a therapeutic modality needed to target the pathogenesis of diabetic retinopathy. Significance of the Research: In the United States alone, approximately 60% of those patients diagnosed with type 2 diabetes for 20 years have diabetic retinopathy. Health care expenditures associated with diabetic retinopathy increases as the severity of the disease progresses. The main stay of treatment of proliferative diabetic retinopathy is photocoagulation, the use of VEGF inhibitors, and tight glucose control. Photocoagulation and VEGF inhibitors are expensive and invasive treatment modalities. This study will explore a less expensive alternative to target free radicals, with the specific aim of exploring its efficacy in reducing the rate of progression of nonproliferative diabetic retinopathy to the potentially blinding proliferative type. Primary Hypothesis: 1. Patients who receive oral administration of alpha lipoic acid 600 mg daily will experience decreased progression of retinopathy compared to patient who did not. Decrease in progression of retinopathy has been demonstrated by measuring the levels of inflammatory cytokines. - The hypothesis stems from scientific evidence that certain cytokines such as M-CSF, interleukin 6 and 8 levels are elevated in patients with diabetic retinopathy. Evidence of suppressed inflammatory cytokines will be an indication for decreased progression of retinopathy. 2. Preservation of visual acuity and retinal thickness of patients, with moderate diabetic retinopathy, who received oral administration of alpha lipoic acid 600 mg. Secondary hypothesis: 1. Patients who receive oral administration of alpha lipoic acid 600 mg daily will have higher blood level of glutathione than those who did not. - The hypothesis stems from the evidence that elevated levels of glutathione is maintained in the presence of alpha lipoic acid. Maintained elevated levels of glutathione will suggest the activity and efficacy of alpha lipoic acid. Outcome Variables: Primary Outcome Variables: 1. Decreased progression of diabetic retinopathy as measured and graded by using Standard ETDRS 7 –field color stereoscopic funds photograph, and also by measuring the levels of interleukin 6, 8 and M-CSF using flow cytometer 2. Changes in retinal thickness and visual acuity as measured by Optical coherence tomography (OCT) and Electronic Visual Testing algorithm respectively Secondary Outcome Variable: 1. Changes in the plasma level of glutathione as measured by Tandem-Mass Spectrometer Timeline for project implementation: Activities Date Protocol Design - Finished IRB Approval - January 2013 (IRB application will be submitted in Ferris State University IRB) Study participant Enrollment - September-2013 Study Ends - 31 December 2014 Data analysis - January-March 2015 Dissemination of Results /Publication April 2015 The names and qualifications of all individuals who are substantially responsible for pursuing the proposal's objectives: 1. ARINZE NKEMDIRIM OKERE, PHARMD, MS (Primary investigator) Assistant Professor of Pharmacy-Ferris State University 2. Avesh Raghunandan, OD, PhD (Co-investigator) Associate Professor of Optometry Michigan College of Optometry, Ferris State University 3.Dean Luplow, OD Associate Professor of Optometry Michigan College of Optometry, Ferris State University Dissemination Discuss how you will disseminate the results/findings of your project to the University, community, and/or your greater academic/ professional community. Dissemination plans should also be included in your project timeline on page 4. Additionally, identify your specific plans to report to the Foundation Board of Directors your project results and conclusions (per the RFP requirements). To avoid bias, data will not be released to investigators until the end of the study period. Data analysis will start in January 2015. At the end of April 2015, a manuscript describing the findings of this study will be prepared and submitted for publication in the Journal of American Medical Association. The finished manuscript and summary of the data will be presented to Foundation Board of Directors in April 2015. Budget - Detail how grant funds will be used. The budget should also describe the extent to which any additional resources beyond the Foundation's grant are needed and have been committed to the project. If requesting equipment, assess distribution/disposal upon completion of project. Please list items under the expense categories. **Food and beverage expenses will not be funded by the Foundation. It is not the intent of the grant to fund/provide direct compensation for faculty/staff. Student salaries are considered on a case by case basis** Project Income: Ferris Foundation: 5,000 Department/College: In-Kind (please specify): FSU Faculty Research Grant 14,000 Other Sources (please specify): Total Project Expenses: Ferris Foundation Department/College Other Sources In-Kind Subtotal Salaries/Personnel Costs Supplies and Materials 200 200 6,800 11,800 Travel & Transportation 1,000 1,000 Other 6,000 6,000 14,000 19,000 Equipment 5,000 TOTAL Budget Narrative Explain estimated income and expenses listed on the previous page. For ongoing projects, please include a discussion financial sustainability of the project or initiative. Analysis Cost: Budget: Materials & Supplies (Papers, printing flyers, envelops, etc) Subtotal = $200 Travel Costs (List destination(s), costs & subtotal) Subtotal = $1000 Contractual/Technical Services (Flow cytometer and Tandem Mass Spectrometry evaluation of blood samples for inflammatory cytokines) Subtotal = $6000 Equipment (Dry ice maker: $1500 Alpha Lipoic acid: $10,300) Subtotal = $11,800 Total $19,000 Submit by Email Print Form