Renal and Peripheral Hemodynamic Function in Patients With Type 1 Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT00297401|
Recruitment Status : Completed
First Posted : February 28, 2006
Last Update Posted : August 29, 2016
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 1||Drug: ruboxistaurin Drug: placebo||Phase 3|
This is a pilot study with 3 parts. Twenty-one patients with type 1 diabetes will be randomized to LY333531 or placebo in a 2:1 fashion. Each patient will be studied on four occasions, while euglycemic and while hyperglycemic without PKC inhibition and while euglycemic and hyperglycemic after an eight-week period of PKC inhibition.
Study Part 1: The impact of PKC inhibition on the renal and peripheral hemodynamic response to hyperglycemia On the evening prior to the first study day, the study participants will be admitted to an in-patient research facility with overnight plasma glucose levels maintained at 4-6 mmol/L using a modified glucose clamp technique. The next day, baseline measures of endothelial function and vascular compliance, mean arterial pressure (MAP), and renal function, including glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal blood flow (RBF), filtration fraction (FF) and renal vascular resistance (RVR) will be obtained using inulin and para-aminohippurate. In all diabetic subjects, euglycemia or hyperglycemia will be maintained by modified overnight glucose clamping techniques. During the second day of the study, capillary blood glucose will be maintained at 9-11 mmol/l overnight, and the renal and peripheral vascular hemodynamic measurements will be repeated the following day. The subjects will then be given the PKC-inhibitor LY333531 (or placebo) for 6 weeks, after which the study will be repeated. The first dose of LY333531 will be taken at 0800 hrs the day after the completion of Study 1 The dose will consist of 32 mg PO OD. Study participants will monitor their capillary blood glucose levels on a four times daily schedule.
Study Part 2: The impact of PKC inhibition on the response to Ang II On the evening prior to the first study day, the study participants will be admitted to an in-patient research facility with overnight plasma glucose levels maintained at 4-6 mmol/L using a modified glucose clamp technique. The next day, baseline measures of renal function, including GFR, ERPF, RBF, FF and RVR will be obtained. Graded Ang II infusion will be administered, and the response of MAP, GFR, RPF, RBF, FF and RVR will be measured. The subjects will then be given the PKC-inhibitor LY333531 (or placebo) for 8 weeks, as previously described, after which the study will be repeated.
Study Part 3: The impact of PKC inhibition on proteinuria . Subjects will collect a 24 hour urine sample for protein / albumin excretion. They will subsequently be randomized to receive either the PKC inhibitor LY333531 or placebo, using a table of random numbers. After 8 weeks treatment, the 24 hour urine sample will again be collected.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||The Effect of Protein Kinase C Inhibition on Renal and Peripheral Hemodynamic Function in Patients With Type 1 Diabetes Mellitus|
|Study Start Date :||March 2006|
|Actual Primary Completion Date :||November 2007|
|Actual Study Completion Date :||November 2007|
32 mg, QD, PO, up to 8 weeks
|Placebo Comparator: 2||
QD, PO, up to 8 weeks
- Primary outcomes will be the change in proteinuria, pre- and post-treatment with ruboxistaurin. [ Time Frame: Baseline and 8 weeks ]
- Change in the renal and peripheral pressor response to hyperglycemia pre and post treatment with ruboxistaurin [ Time Frame: Baseline and 8 weeks ]
- Change in the renal and peripheral pressor response to Angiotensin II pre and post-treatment with ruboxistaurin. [ Time Frame: Baseline and 8 weeks ]
- Secondary analyses will consist of the change in endothelial function and vascular compliance pre- and post-treatment with ruboxistaurin. [ Time Frame: Baseline and 8 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00297401
|For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physcian.|
|Toronto, Ontario, Canada|
|Study Director:||Karl Beutner||Chromaderm, Inc.|