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

• ClinicalTrials.gov Identifier: NCT00442767
• Recruitment Status: Completed
• First Posted: March 2, 2007
• Results First Posted: July 10, 2018
• Last Update Posted: July 10, 2018
• Sponsor: Montefiore Medical Center
• Collaborator: Amylin Pharmaceuticals, LLC.
• Information provided by (Responsible Party): Rubina Heptulla, Montefiore Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: Insulin; Drug: Pramlintide + Insulin	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reducing Postprandial Hyperglycemia With Adjuvant Premeal Pramlintide and Postmeal Insulin in Children With Type 1 Diabetes Mellitus.
• Study Start Date: February 2007
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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	Drug: Insulin; 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.; Other Name: aspart or lispro
Experimental: 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%.	Drug: Pramlintide + 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%.; Other Name: Pramlintide Acetate

Outcome Measures

Primary Outcome Measures :

1. Assess the Mean Area Under the Curve (AUC) for Blood Glucose Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone [ Time Frame: 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 Outcome Measures :

1. Measure of Glucagon Concentration in Subjects Treated With Pramlintide + Insulin, Compared to Insulin Alone. [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Sponsors and Collaborators

Montefiore Medical Center

Amylin Pharmaceuticals, LLC.

Investigators

• Principal Investigator: Rubina A Heptulla, MD; Montefiore Medical Center

More Information

Publications:

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.

• Responsible Party: Rubina Heptulla, Principal Investigator, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT00442767
• Other Study ID Numbers: H-18629; GCRC protocol #:0954
• First Posted: March 2, 2007
• Results First Posted: July 10, 2018
• Last Update Posted: July 10, 2018
• Last Verified: June 2018

Keywords provided by Rubina Heptulla, Montefiore Medical Center:

pediatric; juvenile; diabetes mellitus; Pediatric type 1 diabetes mellitus

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Pramlintide; Islet Amyloid Polypeptide; Hypoglycemic Agents; Physiological Effects of Drugs; Appetite Depressants; Anti-Obesity Agents; Amylin Receptor Agonists; Molecular Mechanisms of Pharmacological Action