Phase I: We demonstrate here our capabilities to recruit insulin dependent (IDD) patients and our expertise and experience in treating such patients in a research setting (clinical trial) similar to that envisioned by the RFA. A controlled and randomized clinical trial with IDD kidney recipients to test the hypothesis of a casual relationship between the dysmetabolism of IDD and renal vascular disease has been underway and conducted by us for the last three years. During this period we have acquired experience about problems of trial design, patient adherence (major problem), methods of monitoring hyperglycemia, and of treatment (11 patient-years experience of insulin pumps), etc. We demonstrate our commitment to diabetic research, our ideal clinical research environment and our willingness to collaborate with the NIAMDD. The long interest of our ophthalmologists in diabetes research is also pointed out. Phase II: We present our version of the Manual of Operations for the randomized feasibility study, based on our extensive experience obtained from the ongoing clinical trial. We illustrate this experience with examples at all levels of the trial, i.e., problems in recruiting, adherence, monitoring, standard and strict treatments, etc. We propose to ascertain for the feasibility study 10 IDD patients without retinopathy, match them for age, sex, duration of disease, beta cell function, and HLA and randomize them to standard and maximized control groups. We shall study the major endpoints of retinopathy, neuropathy and possible exercise induced proteinuria and renal histology during the 2 years of the feasibility study. If we succeed in achieving and maintaining a clear difference of control between the 2 groups we would have by then 2 years of the fullscale trial completed in these 10 patients.
