Type 1 Diabetes Mellitus
Conditions
Keywords
pediatric, juvenile, diabetes mellitus, Pediatric type 1 diabetes mellitus
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.
Interventions
DRUGInsulin
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, before meal.
DRUGPramlintide + Insulin
30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%.
Sponsors
Amylin Pharmaceuticals, LLC.
Montefiore Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone | 0 to 240 minutes post-dose | Blood glucose concentration in terms of mean AUC (0 to 240 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone. | 0 to 120 minutes post-dose | Glucagon concentration in terms of mean AUC (0 to 120 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone |
Countries
United States
Participant flow
Recruitment details
Eight study subjects were screened and all subjects completed both study visits.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Therpy / Pramlintide + Insulin Therapy Rapid acting Insulin therapy - before meal: 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, before meal.
Pre-meal Pramlintide and Post-meal Insulin therapy: 30mcg of pramlintide was administered subcutaneously immediately prior to the meal and insulin was given 15 minutes after the meal. The dose of insulin was reduced by 20%. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Insulin Therpy / Pramlintide + Insulin Therapy |
|---|---|
| Age, Categorical <=18 years | 8 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 16.2 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone
Blood glucose concentration in terms of mean AUC (0 to 240 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone
Time frame: 0 to 240 minutes post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rapid Acting Insulin Therapy - Before Meal | Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone | 205 mmol*L/min | Standard Error 116 |
| Pre-meal Pramlintide and Post-meal Insulin Therapy | Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone | 993 mmol*L/min | Standard Error 141 |
Secondary
Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone.
Glucagon concentration in terms of mean AUC (0 to 120 minutes) was determined in subjects treated with Pramlintide + Insulin vs. Insulin alone
Time frame: 0 to 120 minutes post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rapid Acting Insulin Therapy - Before Meal | Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone. | 6060 ng*L/min | Standard Error 459 |
| Pre-meal Pramlintide and Post-meal Insulin Therapy | Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone. | 7575 ng*L/min | Standard Error 479 |