Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus

Montefiore Medicine Academic Health System

Status and phase: Completed; Phase 4

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Pramlintide + Insulin; Drug: Insulin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00442767

H-18629

GCRC protocol #:0954

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 12 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Rapid acting Insulin therapy - before meal

Active Comparator group

Description:

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

Treatment:

Drug: Insulin

Pre-meal Pramlintide and Post-meal Insulin therapy

Experimental group

Description:

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%.

Treatment:

Drug: Pramlintide + Insulin