Ignite Creation Date:
2024-05-05 @ 4:42 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00297401
Status:
COMPLETED
Last Update Posted:
2016-08-29
First Post:
2006-02-24
Brief Title:
Renal and Peripheral Hemodynamic Function in Patients With Type 1 Diabetes Mellitus
Sponsor:
Chromaderm Inc
Organization:
Chromaderm Inc
Study Overview
Official Title:
The Effect of Protein Kinase C Inhibition on Renal and Peripheral Hemodynamic Function in Patients With Type 1 Diabetes Mellitus
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Protein kinase C PKC an enzyme in the body has been implicated in the process of diabetic microvascular complications The purpose of this study will be to evaluate the renal hemodynamic and peripheral vascular effects of PKC inhibition with ruboxistaurin mesylate an inhibitor of PKC in patients with Type 1 diabetes mellitus and evidence of early nephropathy In this pilot study 21 patients with type 1 diabetes were planned to be randomized to LY333531 or placebo in a 21 fashion after an initial period of testing After 8 weeks of study drug patients were retested
Detailed Description:
This is a pilot study with 3 parts Twenty-one patients with type 1 diabetes will be randomized to LY333531 or placebo in a 21 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 mmolL 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 mmoll 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 mmolL 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 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 mmolL 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 mmoll 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 mmolL 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| B7A-CA-S003 | None | None | None |