Clinical trial NCT00460304: The Effect of Pramlintide on Meal Time Insulin Bolus
Official title: The Effect of Pramlintide on Meal Time Insulin Bolus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Type I diabetes
Insulin pump
Continuous glucose monitoring
Insulin to carbohydrate ratio
Correction factor
Pramlintide
Lead sponsor: Diabetes Care Center
Sponsor class: INDUSTRY
Collaborators: name: Amylin Pharmaceuticals, LLC.
First posted: 2007-04-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to establish the mean percentage of change in the insulin-to-carbohydrate ratio due to pramlintide treatment once a maximum tolerated dose or 6 mcg before each meal is reached. The secondary objective is to establish which insulin bolus wave form is associated with the lowest post-bolus without hypoglycemia in subjects treated with maximum pramlintide dosage.

Detailed description: Pramlintide. an amylinomimetic, is effective in reducing post-meal glucose by non-insulin means. As such, when patients requiring insulin treatment are treated with pramlintide, the bolus insulin does must be reduced. Current recommendations suggest a 50% reduction but in our experience and that of a recent study this appears excessive. By using continuous glucose monitoring(CGM) to guide pre-meal insulin treatment, we will determine the percentage reduction in meal time insulin bolus comparing pre-pramlintide to maximum pramlintide treatment. We anticipate that the reduction in bolus dosage will be about 25%. In addition, the secondary aim of this study is to determine which bolus pattern, standard, square or dual wave, provides the best post-meal glucose control with pramlintide therapy.

Eligibility criteria: Inclusion Criteria:

* Age: \>17
* Type I diabetes
* Onset of diabetes \>3 months
* Use of insulin pump \>3 months
* Hb A1C \<8.9%
* Demonstrated compliance to clinic visits
* Demonstrated knowledge and use of bolus dosing calculations, carbohydrate counting, use of insulin pump and blood glucose meter
* Monitor blood glucose \>4/day

Exclusion Criteria:

* Pregnancy or nursing
* Recent (within last 3 months) factor that may cause change in insulin sensitivity, e.g. severe emotional or physical stress, recent significant infection or surgery. etc.
* Renal failure (creatinine \>1.5 mg/dl
* Symptomatic gastroparesis
* Using a medication that would interfere with insulin sensitivity
* Treatment with extenatide or DPP IV inhibitor within the last 4 weeks
* HbA1C change \>0.9 % within the last 3 months
* Significant change in eating or activity pattern
* Weight change of \>1.9 kg within the last 3 months
* ALT \>3 times upper limits of normal

Primary outcomes:
measure: The mean ICR from Vist 3a-e and 4a-e will be compared. Percentage reduction of ICR will be calculated. From these the mean ICR will be calculated.
timeFrame: 12-10-07
Secondary outcomes:
measure: The mean post-meal glucose from the four hour period after beginning a meal will be averaged for each bolus wave form. Then the three wave form mean glucose results will be compared.
timeFrame: 12-10-07
Other outcomes:
Locations:
Study officials:
affiliation: Diabetes Care Center
name: Allen B King, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes Care Center
name: Gary S Wolfe, RN, CCM
role: STUDY_DIRECTOR
References:
citation: Edelman S, Garg S, Frias J, Maggs D, Wang Y, Zhang B, Strobel S, Lutz K, Kolterman O. A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Diabetes Care. 2006 Oct;29(10):2189-95. doi: 10.2337/dc06-0042.
citation: Symlin (package insert) San Diego, CA Amylin Pharmacetucials. 2005
citation: King AB, Armstrong DU. Basal bolus dosing: a clinical experience. Curr Diabetes Rev. 2005 May;1(2):215-20. doi: 10.2174/1573399054022794.
citation: King AB, Armstrong DU. A prospective evaluation of insulin dosing recommendations in patients with type 1 diabetes at near normal glucose control: Basal dosing. J Diabetes Sci Technol. 2007 Jan;1(1):36-41. doi: 10.1177/193229680700100106.
citation: King AB, Armstrong DU. A prospective evaluation of insulin dosing recommendations in patients with type 1 diabetes at near normal glucose control: bolus dosing. J Diabetes Sci Technol. 2007 Jan;1(1):42-6. doi: 10.1177/193229680700100107.
citation: Young AA, Gedulin B, Vine W, Percy A, Rink TJ. Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia. 1995 Jun;38(6):642-8. doi: 10.1007/BF00401833.
citation: Gedulin BR, Rink TJ, Young AA. Dose-response for glucagonostatic effect of amylin in rats. Metabolism. 1997 Jan;46(1):67-70. doi: 10.1016/s0026-0495(97)90170-0.
citation: Rushing PA, Lutz TA, Seeley RJ, Woods SC. Amylin and insulin interact to reduce food intake in rats. Horm Metab Res. 2000 Feb;32(2):62-5. doi: 10.1055/s-2007-978590.
citation: Gross TM, Mastrototaro JJ. Efficacy and reliability of the continuous glucose monitoring system. Diabetes Technol Ther. 2000;2 Suppl 1:S19-26. doi: 10.1089/15209150050214087. No abstract available.