Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Type 1 Diabetes

Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Volunteers With Type 1 Diabetes

The investigators are doing this research study to find out if the type of needle used to administer them affects the speed with which insulin and glucagon get into the blood. The investigators will compare a traditional insulin needle to an injection device, called the MicronJet, that uses microneedles to deliver medication into the top layer of your skin.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Procedure: Intradermal injection; Procedure: Subcutaneous injection

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older with clinical type 1 diabetes for at least one year
• Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins including insulin aspart (Novolog), insulin lispro (Humalog), and insulin glulisine (Apidra).
• Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 5 units of rapid acting insulin
• Stimulated C-peptide <0.1 nmol/L at 90 minutes after liquid mixed meal tolerance test.

Exclusion Criteria:

• Unable to provide informed consent
• Unable to comply with study procedures
• Current participation in another diabetes-related clinical trial other than one that is primarily observational in nature. Potential subjects enrolled in trails of passive monitoring equipment, such as continuous glucose monitors (CGMs), are not excluded
• Inadequate venous access as determined by study nurse or physician at time of screening
• Pregnancy
• Hemoglobin less than 13.5 for men and less than 12 for women
• History of pheochromocytoma (fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor to include episodic or treatment refractory hypertension defined as requiring 4 or more medications to achieve normotension, paroxysms of tachycardia, pallor, or headache, or personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease)
• History of adverse reaction to glucagon (including allergy) besides nausea and vomiting
• History of adrenal disease or tumor
• Hypertension (blood pressure > 160/100 mm/Hg at screening or day of study visit
• History of allergy to aspirin or any history of aspirin intolerance, including Reye's syndrome, or gastric ulcer or bleeding associated with salicylates.
• Blood dyscrasia or bleeding diathesis, such as hemophilia, Von Willebrand's disorder, and idiopathic thrombocytopenic purpura (ITP)
• Peptic Ulcer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intradermal first; Intradermal injection experiment first, followed by subcutaneous injection experiment	Procedure: Intradermal injection; Procedure: Subcutaneous injection
Experimental: Subcutaneous first; Subcutaneous injection experiment first, followed by intradermal injection experiment	Procedure: Intradermal injection; Procedure: Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)	1 day

Secondary Outcome Measures

Outcome Measure	Time Frame
Aggregate mean difference in t1/2max between the methods	1 day visit
Aggregate mean difference in Cmax between the methods	1 day
Aggregate mean difference in area under the curve (AUC) between methods	1 day
AUC of 0-1 hour (and by subtraction hours 1-5)	1 day
AUC of 0-2 hours (and by subtraction hours 2-5)	1 day
Time to 50% of Total AUC (or said another way, time to 50% exposure)	1 day
Fraction of subjects with difference in tmax between the methods of > 25%	1 day
Fraction of "dry" injections with no reflux of fluid from the injection site	1 day
Difference in mean visual analog pain score between the two methods	1 day
Difference in mean visual analog pain score between insulin and glucagon with subcutaneous injection	1 day
Difference in mean visual analog pain score between insulin and glucagon with intradermal injection	1 day

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 23, 2012
• First Submitted That Met QC Criteria: September 12, 2012
• First Posted (Estimate): September 13, 2012

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: September 6, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; glucagon; insulin; microneedle; intradermal
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2012P001098