Clinical trial NCT00442767: Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
Official title: Reducing Postprandial Hyperglycemia With Adjuvant Premeal Pramlintide and Postmeal Insulin in Children With Type 1 Diabetes Mellitus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: pediatric
juvenile
diabetes mellitus
Pediatric type 1 diabetes mellitus
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Amylin Pharmaceuticals, LLC.
First posted: 2007-03-02
Enrollment: 8
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to examine the effect of pramlintide given pre-meal and insulin given just after a meal vs. standard therapy of pre-meal insulin on post-prandial glucose excursions.

The secondary objective is to examine the effect of pramlintide and insulin on glucagon suppression in type 1 diabetes.

Detailed description: Following approval by the Institutional Review Board at Baylor College of Medicine 8 adolescents (6 males, 2 females) with type 1 diabetes were recruited to the open-labeled, non-randomized, crossover study. Two male subjects were African American; the remaining subjects were all Caucasian. Six subjects were on insulin pump therapy, and the two on insulin glargine, self-administered at -90minutes. Subjects had their last meal before 12 midnight, and stayed at our research center from 7AM until completion of the study at 2PM. Study A was done before study B.

Basal insulin doses of the subjects were kept constant through studies A and B. No subject was prescribed pramlintide any time in the past prior to participation in this study.

Study A:Insulin therapy was continued as per prescribed home regimen without pramlintide. Subjects self-administered a rapid-acting insulin analog (aspart or lispro) bolus based on their individual insulin: carbohydrate ratio, following which they received 12oz (591ml) of Boost High Protein drink (360 calories, 50gms carbohydrate, 12 gms fat) at 9AM (0 minutes). The Boost was consumed in 5 - 7 minutes. Blood samples were collected for the analysis of blood glucose (BG) levels at -60, -30, -10, and 0 minutes, and every 10 minutes thereafter for the first hour, every 20 minutes for the second hour, and every 30 minutes until the study ended. Blood samples were also collected throughout the study at multiple time points for the analysis of insulin and glucagon levels. Subjects were provided with lunch at 2PM, and discharged.

Study B:The study protocol was identical to study A except 30mcg of pramlintide was administered subcutaneously immediately prior to drinking the Boost at 9AM, and no insulin was given before the meal but was given 15 minutes after the meal (9:15AM) and the dose was reduced by 20%. Study B was conducted within 3 to 4 weeks of study A.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes only
* Diagnosed with T1DM for at least 1 year
* HbA1C less than or equal to 8.5%
* Currently treated using insulin glargine with or without Humalog/ Novolog or on the insulin pump
* Hemoglobin equal to or greater than 12mg/dL
* Otherwise healthy, EXCEPT for T1DM and treated hypothyroidism
* Negative pregnancy test, in the case of females

Exclusion Criteria:

* Lack of supportive family
* Evidence or history of chemical abuse
* BMI (body mass index) greater than the 90th percentile OR less than the 10th percentile for age
* Patient who is poorly compliant with current insulin management and/or Prescribed self blood glucose monitoring
* Patient who experiences recurrent severe hypoglycemia episodes (requiring assistance/ hospitalizations) in the past 6 months
* Have hypoglycemia unawareness
* Have a confirmed diagnosis of gastroparesis, and/ or require medications that stimulate gastrointestinal motility
* Pregnant or lactating patients, or patients planning on becoming pregnant

Primary outcomes:
measure: Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone
timeFrame: 0 to 240 minutes post-dose
Secondary outcomes:
measure: Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone.
timeFrame: 0 to 120 minutes post-dose
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Rubina A Heptulla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hassan K, Heptulla RA. Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus. Pediatr Diabetes. 2009 Jun;10(4):264-8. doi: 10.1111/j.1399-5448.2008.00490.x. Epub 2008 Dec 18.