Clinical trial NCT00456300: Role of Exenatide in Type 1 Diabetes
Official title: The Role of Exenatide in Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Hypoglycemia
Hyperglycemia
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2007-04-04
Enrollment: 11
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if giving exenatide and insulin before a meal would lower blood sugars after the meal. This study may help in developing new treatments to help control high blood sugars after meals. This may help improve overall blood sugar control and prevent the long-term effects of diabetes.

Detailed description: A large study in people with type 1 diabetes (T1DM) showed that lowering blood sugars stopped or delayed the occurrence of health problems. As a result of the study, treatment should try to control blood sugars as near to normal as safely possible.

In people without diabetes, the "after meal" blood sugar level is very carefully controlled. Insulin (the hormone that lowers blood sugar) and glucagon (hormone that raises blood sugar) play a key role in keeping this careful balance. It is now known that a substance made by the body called GLP-1 also helps with this careful balance. Glucagon like peptide-1 works in four ways. First, it helps to stimulate the cells in the pancreas to produce more insulin. Secondly, it helps to "dampen" the glucagon response (glucagon is released after a meal and causes the blood sugar to rise). Thirdly, Glucagon like peptide-1 delays the digestion of food in the stomach. Lastly, it seems to "dampen" the appetite, which causes a person to eat less.

Exenatide is a medication that works very similar to Glucagon like peptide-1. Exenatide is FDA approved for use in adults.

Study Design: Followed by a baseline study with insulin alone, subjects were randomized to two different doses of exenatide (1.25 and 2.5 µ,g), administered in a double-blinded randomized controlled manner, along with insulin as a single subcutaneous injection. Studies were at least 3 weeks apart.

Baseline: At 0800 h, the pre-breakfast insulin bolus was administered based on patient's usual insulin-to-carbohydrate ratio. Post-bolus, subjects drank 12 ounces of a standard liquid meal (Boost High Protein Drink, 360 calories, 50 g carbohydrates, and 12 g fat), enriched with 1 g of \[13C\] glucose within 10 min. Breath samples for 13CO2 analysis were collected in duplicates at 17 time points until 1300 h. Usual insulin basal rates or glargine were maintained during study.

On the days subjects received the study drug of 1.25 µ,g (\~0.02 µ,g/kg) or 2.5 µ,g (\~0.04 µ,g/kg) exenatide along with insulin, the prandial insulin was reduced by 20%.

Measurements: Plasma glucose was measured using a bedside YSI glucose analyzer (2300 Stat Plus; Yellow Springs Instruments, Yellow Springs, OH) throughout the study at regularly timed intervals. Delta plasma glucose area under the curve (AUC0 -120) was measured for the exenatide treated groups vs. insulin monotherapy.

Eligibility criteria: Inclusion Criteria:

\*\*\*Subjects must be patients of the Texas Children's Hospital Diabetes Care Center\*\*\*.

All of the following criteria must be met:

1. Between 12-21 years of age at the time of enrollment.
2. Have been diagnosed with Type 1 diabetes for at least 1 year and in good control (HbA1C less than 8.5%).
3. Subjects must be otherwise healthy except for the Type 1 Diabetes and treated hypothyroidism.
4. Menstruating women must have a negative pregnancy test.
5. Hemoglobin equal to or greater than 12 g/dL before each study.
6. Weight greater than 44 kg.
7. Tanner stage greater than 3

Exclusion Criteria:

1. Any chronic disease: leukemia, asthma, inflammatory bowel disease, cystic fibrosis, juvenile rheumatoid arthritis etc or on treatment that might directly or indirectly affect glucose homeostasis, except for diabetes and hypothyroidism; stable on medications.
2. Lack of a supportive family environment as detected by the clinicians and/or social workers.
3. Positive pregnancy test in menstruating young women.
4. BMI greater than 90th percentile for age or less than 10th percentile for age.
5. Lactating and nursing mothers.

Primary outcomes:
measure: Mean Plasma Glucose Area Under the Curve (AUC) for Blood Glucose Concentration in the Exenatide 1.25 mcg or Exenatide 2.5 mcg Treated Groups Along With Insulin, Compared to Insulin Alone
timeFrame: 0-120 minutes post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children's Hospital/ Baylor College of Medicine
state: Texas
Study officials:
affiliation: Montefiore Medical Center
name: Rubina Heptulla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raman VS, Mason KJ, Rodriguez LM, Hassan K, Yu X, Bomgaars L, Heptulla RA. The role of adjunctive exenatide therapy in pediatric type 1 diabetes. Diabetes Care. 2010 Jun;33(6):1294-6. doi: 10.2337/dc09-1959. Epub 2010 Mar 23.