Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00228865
Status:
TERMINATED
Last Update Posted:
2016-08-10
First Post:
2005-09-27
Brief Title:
Clinical Effects of Pulsatile Insulin Delivery on Cognitive Function- Phase 1
Sponsor:
Florida Atlantic University
Organization:
Florida Atlantic University
Study Overview
Official Title:
Effects of Pulsatile IV Insulin on Cognitive Deficits in Diabetic Patients
Status:
TERMINATED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Administrative
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine if restoring normal metabolic function in patients with either Type I or Type II Diabetes can improve overall cognitive function Patients are treated once a week with pulsatile intravenous insulin therapy mimicking normal insulin secretion and high amounts of oral glucose consumption
Detailed Description:
It is known that the glucose metabolic pathway glycolysis is the primary fuel generator in the brain and nerve tissue the heart and vascular tissue the eye the kidney and the liver Deficient metabolic states such as seen in the glucose metabolism of diabetics can lead to sequelae These damaging effects are exacerbated by altered cellular metabolites specifically the increase in catabolic and decrease in anabolic factors It has been shown over the past twenty years that normalization of metabolism in diabetic patients can be accomplished by mimicking the normal endogenous insulin pattern ie in pulses Pulsatile insulin infusion has been demonstrated to reverse the diabetic metabolic state from primary fat utilization to carbohydrate utilization This has been correlated with a stabilization of kidney function in patients with overt diabetic nephropathy stabilization of blood glucoses stabilization of blood pressure patterns and reversal of hypoglycemic unawareness
In patients with cognitive disorders Alzheimers type infusion of intravenous insulin over a short interval hours improves cognitive function Patients with this type of disorder have fewer insulin receptors in the affected areas of brain and insulin resistance by measurement of insulin and glucose levels in spinal fluid This study is designed to study the effects of Pulsatile insulin on patients with diabetes mellitus and impaired cognitive function
Diabetic individuals without other primary causes of cognitive impairment brain tumor previous neurosurgery medications impairing memory and able to swallow without difficulty will undergo pulsatile insulin treatments weekly over a period of 6-12 months with renewals for successive six month periods Serial cognitive studies using Mindstream testing Wechsler Memory Scale II and other localizing cognitive function tests will be done before the start of of treatment and every 3 months thereafterThis study began in 2002 and is continuing
The respiratory quotient RQ is a measurement of CO2 exhaled and O2 inhaled and is proportionate to the fuel sources being used by the body primarily the liver over short periods of time The higher the RQ the more glucose and less alternative fuel sources are being utilized Following the RQ change helps determine the effectiveness of physiological insulin administration in increasing anabolic functions in diabetic individuals By improving the bodys glucose metabolism and thereby causing beneficial effects of anabolic factors the possibility of serious complications can be decreased In addition the use of oral carbohydrate at the same time along with the physiologic insulin administration stimulates the appropriate gut hormones which augment this effect a response which cannot be duplicated with intravenous glucose The purpose of our studies is to induce the physiologic administration of insulin along with the augmenting effect of oral carbohydrates and by returning the normal fuel and organ metabolism as noted by RQ changes evaluate its effectiveness in altering the deleterious effects on bodily functions in diabetic individuals
The RQ is determined by the use of a metabolic cart Individuals breathe into a mask for 3-5 minutes after a rest period of 30 or more minutes The ratio of exhaled volume of CO2 to the inhaled volume of O2 is determined as the RQ The physiologic range is 07 to13 Individuals using fat as a primary fuel have a ratio of 07 protein or mixed fuels is 08-09 and carbohydrate is 09-10 Those taking excessive calories will have RQs higher than 105 The RQ can be followed serially and this is before and after each treatment Three treatments are given during each visit to the center The amount of intravenous insulin and oral glucose given is determined by the RQ changes during the previous treatment
The treatment encourages the glucose metabolism in diabetics to normalize in multiple organs especially muscle retina liver kidney and nerve endings The process fundamentally requires the administration of high dose insulin pulses similar to those found in non diabetic humans by their pancreas into the surrounding portal circulation Oral carbohydrates are given simultaneously to augment the process and prevent hypoglycemia The process is monitored by frequent glucose levels and respiratory quotients RQ RQ is measured by a metabolic cart which determines the ratio VCO2 VO2 This ratio is specific for the fuel used at any one time by the body The glucose levels are monitored to keep glucose levels appropriate and the RQ determines the need to readjust the infusion protocol in each patient for subsequent insulin infusion sessions
In patients with cognitive disorders Alzheimers type infusion of intravenous insulin over a short interval hours improves cognitive function Patients with this type of disorder have fewer insulin receptors in the affected areas of brain and insulin resistance by measurement of insulin and glucose levels in spinal fluid This study is designed to study the effects of Pulsatile insulin on patients with diabetes mellitus and impaired cognitive function
Diabetic individuals without other primary causes of cognitive impairment brain tumor previous neurosurgery medications impairing memory and able to swallow without difficulty will undergo pulsatile insulin treatments weekly over a period of 6-12 months with renewals for successive six month periods Serial cognitive studies using Mindstream testing Wechsler Memory Scale II and other localizing cognitive function tests will be done before the start of of treatment and every 3 months thereafterThis study began in 2002 and is continuing
The respiratory quotient RQ is a measurement of CO2 exhaled and O2 inhaled and is proportionate to the fuel sources being used by the body primarily the liver over short periods of time The higher the RQ the more glucose and less alternative fuel sources are being utilized Following the RQ change helps determine the effectiveness of physiological insulin administration in increasing anabolic functions in diabetic individuals By improving the bodys glucose metabolism and thereby causing beneficial effects of anabolic factors the possibility of serious complications can be decreased In addition the use of oral carbohydrate at the same time along with the physiologic insulin administration stimulates the appropriate gut hormones which augment this effect a response which cannot be duplicated with intravenous glucose The purpose of our studies is to induce the physiologic administration of insulin along with the augmenting effect of oral carbohydrates and by returning the normal fuel and organ metabolism as noted by RQ changes evaluate its effectiveness in altering the deleterious effects on bodily functions in diabetic individuals
The RQ is determined by the use of a metabolic cart Individuals breathe into a mask for 3-5 minutes after a rest period of 30 or more minutes The ratio of exhaled volume of CO2 to the inhaled volume of O2 is determined as the RQ The physiologic range is 07 to13 Individuals using fat as a primary fuel have a ratio of 07 protein or mixed fuels is 08-09 and carbohydrate is 09-10 Those taking excessive calories will have RQs higher than 105 The RQ can be followed serially and this is before and after each treatment Three treatments are given during each visit to the center The amount of intravenous insulin and oral glucose given is determined by the RQ changes during the previous treatment
The treatment encourages the glucose metabolism in diabetics to normalize in multiple organs especially muscle retina liver kidney and nerve endings The process fundamentally requires the administration of high dose insulin pulses similar to those found in non diabetic humans by their pancreas into the surrounding portal circulation Oral carbohydrates are given simultaneously to augment the process and prevent hypoglycemia The process is monitored by frequent glucose levels and respiratory quotients RQ RQ is measured by a metabolic cart which determines the ratio VCO2 VO2 This ratio is specific for the fuel used at any one time by the body The glucose levels are monitored to keep glucose levels appropriate and the RQ determines the need to readjust the infusion protocol in each patient for subsequent insulin infusion sessions
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