The Role of Amylin and Glucagon in T1DM
Information source: Baylor College of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 1 Diabetes
Intervention: Pramlintide and glucagon (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Baylor College of Medicine Official(s) and/or principal investigator(s): Rubina Heptulla, MD, Principal Investigator, Affiliation: Baylor College of Medicine
Summary
The purpose of this study is to see if giving pramlintide and insulin before a meal would
lower high blood sugar and if a glucagon (a naturally made hormone in the body but reduced
in diabetes and its role is in prevention of low blood sugar) shot given in the late "after
meal" time would prevent low blood sugar. The studies outlined in this proposal might help
in developing new treatment options to target "after meal" high blood sugar and before meal
low blood sugar in children. This would possibly help improve overall blood sugar control
and prevent the long-term complications of diabetes.
Clinical Details
Official title: The Role of Amylin and Glucagon in the Management of Normalizing Glucose Excursions in Children With Type 1 Diabetes
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Area under the curve for glucose
Secondary outcome: Glucagon and gastric emptying
Detailed description:
Objective: To develop a new treatment approach in the prevention of hypo and hyperglycemia
in children with type 1diabetes.
Background/Rationale: The diabetes control and complications trial (DCCT) showed that
improving blood sugar control for individuals with type 1 diabetes (T1DM) stopped or delayed
the onset of long-term complications. As a result of the study, intensive management to
control blood sugar and glycosylated hemoglobin as near to normal as safely as possible is
advocated. However, hypoglycemia was increased 3 fold in the DCCT study and is the major
limiting factor in gaining “tight” control of blood sugar in T1DM.
Description of Project: In health individuals, “after meal” blood sugar level is very
carefully controlled. Insulin (the hormone that lowers blood sugar) and glucagon (the
hormone that raises blood sugar) play a key role in maintaining this careful balance.
Recently we understand that a hormone called amylin also contributes to this careful after
meal blood glucose balance. Amylin in the immediate after meal period works by reducing
glucagon, which in turn reduces the liver releasing stored sugar into the blood stream.
In T1DM, there is the lack of insulin and failure of glucagon suppression leading to
hyperglycemia immediately following when food is eaten. Also, glucagon is not regulated
correctly after a meal. The glucagon normally produced by the body does not increase in
response to hypoglycemia thus interfering with the delicate balance between glucose
production and glucose used. Therefore, it is difficult to get normal blood sugar when
someone has type1 diabetes.
Currently, the treatment for mild to moderate hypoglycemia causing a sudden feeling of
racing heart, feeling sweaty, weak or hungry is to eat or drink carbohydrate in the awake
person. Severe hypoglycemia (unconsciousness due to low blood sugar) is treated with a
glucagon shot. Unfortunately, there are no treatments to prevent mild or severe
hypoglycemia.
The purpose of this study is to see if giving pramlintide (manmade amylin) and insulin
before a meal would lower hyperglycemia and if a glucagon shot given in the late “after
meal” time would prevent hypoglycemia and allow the blood sugar levels to improve in people
with T1DM. The studies outlined in this proposal might help in developing new treatment
options to target “after meal” hyperglycemia high blood glucose and before meal hypoglycemia
in children. This study for the first time will investigate the role of glucagon in the
causation of hyperglycemia and its role in the prevention of hypoglycemia.
Relevance to Type 1 diabetes: Using naturally occurring hormones that are dysregulated or
deficient in T1DM we wish to restore normal glucose concentration in T1DM. Such treatment if
successful would be a major breakthrough in the prevention of hyper and hypoglycemia and in
decreasing both short and long-term complications associated with T1DM.
Eligibility
Minimum age: 12 Years.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Age >12 years < 19 years
2. Have diabetes for at least 2 years and in good control (HbA1C < 8%).
3. Be on continuous subcutaneous insulin infusion using an insulin pump.
4. Subjects must be otherwise healthy except for their T1DM and treated for
hypothyroidism.
5. Menstruating women must have negative pregnancy test.
6. Hemoglobin equal to or > than 12 g/dL before each study.
7. Weight more than 44 kg.
Exclusion Criteria:
1. Age >18 or < 12 y at the time of study
2. Any chronic disease (leukemia, asthma, inflammatory bowel disease, cystic fibrosis,
juvenile rheumatoid arthritis, etc that directly, or as a result of treatment,
directly or indirectly affect glucose homeostasis
3. Hemoglobin less than 12 g/dl (If before any of the studies the hemoglobin is lower
than 12 g/dl, subjects will be excluded from further studies)
4. Lack of a supportive family environment
5. Positive pregnancy test in menstruating young women
6. Evidence or history of chemical abuse
7. Hgb A1c >8. 0 % in a diabetic subject
8. BMI > 90 % tile for age or < 10 % tile for age
9. Allergy to local anesthetics (ELAMAX Cream)
10. Weight less than 44 kg
11. Children of staff members
Locations and Contacts
Baylor College of Medicine, Houston, Texas 77030, United States
Additional Information
Learn about the physiology of amylin
Starting date: July 2002
Last updated: June 19, 2006
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