Ignite Creation Date:
2024-05-05 @ 6:33 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00505882
Status:
WITHDRAWN
Last Update Posted:
2019-01-08
First Post:
2007-07-24
Brief Title:
Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
The Pilot StudyEfficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
Status:
WITHDRAWN
Status Verified Date:
2019-01
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:
In this pilot study we are evaluating the efficacy of pramlintide on preventing weight gain among early onset type 1 diabetes We are also evaluating the safety and the effects of treatment with pramlintide on early diagnosed type 1 diabetic subjects especially among pediatric subjects
Detailed Description:
The autoimmune process along with a strong genetic-mediated destruction and dysfunction of pancreatic β-cells are the main pathogeneses of type 1 diabetes These processes cause absolute and relative insulin and amylin deficiencies For the last decades insulin therapy has been the primary therapy for type 1 diabetes
Amylin is a 37 amino acid peptide hormone co-secreted with insulin mostly by the pancreatic β cells in response to meals Amylin has several known effects including suppression of postprandial glucagon secretion regulation of gastric emptying and reduction of food intake Pramlintide is an amylin analog recently approved by the Food and Drug Administration FDA to be given at meal time as an adjunct to insulin therapy in patients with type 1 or type 2 diabetes who have failed to achieve desired glucose control despite optimal insulin therapy or insulin therapy with or without a sulfonylurea agent andor metformin Several clinical trials showed that meal time amylin replacement with pramlintide along with insulin therapy improved post-prandial hyperglucagonemia and reduced post-prandial glucose excursion A recent randomized control trial showed that pramlintaide reduced weight by up to 2kg in both type 1 and type 2 diabetes
The Diabetes Control and Complications Trial DCCT demonstrated that intensive diabetes therapy delays the onset and progression of microvascular disease such as retinopathy nephropathy and neuropathy The DCCT also showed that the prevalence of obesity defined as a body mass index BMI 278 kgm2 for men and 273 kgm2 for women was 331 in the intensive treatment group compared with 191 in the conventional treatment group Intensively treated patients gained an average of 475 kg more than conventionally treated patients P 00001 Weight gain was most rapid during the first year of therapy Several mechanisms have been proposed to explain the weight gain associated with insulin therapy These include decreased glycosuria due to improved glycemic control the direct lipogenic effects of insulin on adipose tissue and increased food intake due to recurrent mild hypoglycemia
Obesity especially in type 2 diabetes is associated with the accumulation of triglyceride in muscle as well as in the liver These are thought to cause insulin resistance and diabetic metabolic complications Sub-analysis of the DCCT showed that in the intensive treatment group higher weight gain correlated with a higher waist to hip ratio as well as higher LDL and lower HDL levels similar to what is seen in the metabolic syndrome An association between weight gain due to intensive insulin therapy in type 1 diabetes and the risk of coronary artery disease has yet to be determined However the DCCT showed some reduction in cardiovascular risk factors among the intensive treatment group as well as reduction in cardiovascular events The DCCT did not evaluate cardiovascular risk based on degree of obesity within the intensive insulin treatment group
The DCCT has shown that the intensive insulin therapy group maintained a higher stimulated C-peptide level than the conventional group Preserving β cell function even modest levels of activity can be advantage in preventing hypoglycemic episodes and also reducing the incidence of retinopathy and nephropathy No study to date has been designed to analyze the effect of pramlintide treatment on the preservation of β cell function in newly diagnosed type 1 diabetic subjects
This pilot study will evaluate the effect of pramlintide on the prevention of weight gain and its effects on beta cell function among early onset type 1 diabetes patients Early onset is defined as those who are diagnosed with type 1 diabetes six to twelve months prior to entry in this study
Amylin is a 37 amino acid peptide hormone co-secreted with insulin mostly by the pancreatic β cells in response to meals Amylin has several known effects including suppression of postprandial glucagon secretion regulation of gastric emptying and reduction of food intake Pramlintide is an amylin analog recently approved by the Food and Drug Administration FDA to be given at meal time as an adjunct to insulin therapy in patients with type 1 or type 2 diabetes who have failed to achieve desired glucose control despite optimal insulin therapy or insulin therapy with or without a sulfonylurea agent andor metformin Several clinical trials showed that meal time amylin replacement with pramlintide along with insulin therapy improved post-prandial hyperglucagonemia and reduced post-prandial glucose excursion A recent randomized control trial showed that pramlintaide reduced weight by up to 2kg in both type 1 and type 2 diabetes
The Diabetes Control and Complications Trial DCCT demonstrated that intensive diabetes therapy delays the onset and progression of microvascular disease such as retinopathy nephropathy and neuropathy The DCCT also showed that the prevalence of obesity defined as a body mass index BMI 278 kgm2 for men and 273 kgm2 for women was 331 in the intensive treatment group compared with 191 in the conventional treatment group Intensively treated patients gained an average of 475 kg more than conventionally treated patients P 00001 Weight gain was most rapid during the first year of therapy Several mechanisms have been proposed to explain the weight gain associated with insulin therapy These include decreased glycosuria due to improved glycemic control the direct lipogenic effects of insulin on adipose tissue and increased food intake due to recurrent mild hypoglycemia
Obesity especially in type 2 diabetes is associated with the accumulation of triglyceride in muscle as well as in the liver These are thought to cause insulin resistance and diabetic metabolic complications Sub-analysis of the DCCT showed that in the intensive treatment group higher weight gain correlated with a higher waist to hip ratio as well as higher LDL and lower HDL levels similar to what is seen in the metabolic syndrome An association between weight gain due to intensive insulin therapy in type 1 diabetes and the risk of coronary artery disease has yet to be determined However the DCCT showed some reduction in cardiovascular risk factors among the intensive treatment group as well as reduction in cardiovascular events The DCCT did not evaluate cardiovascular risk based on degree of obesity within the intensive insulin treatment group
The DCCT has shown that the intensive insulin therapy group maintained a higher stimulated C-peptide level than the conventional group Preserving β cell function even modest levels of activity can be advantage in preventing hypoglycemic episodes and also reducing the incidence of retinopathy and nephropathy No study to date has been designed to analyze the effect of pramlintide treatment on the preservation of β cell function in newly diagnosed type 1 diabetic subjects
This pilot study will evaluate the effect of pramlintide on the prevention of weight gain and its effects on beta cell function among early onset type 1 diabetes patients Early onset is defined as those who are diagnosed with type 1 diabetes six to twelve months prior to entry in this study
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