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

Condition(s) targeted: Type 1 Diabetes

Intervention: Intradermal injection (Procedure); Subcutaneous injection (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
Steven J Russell, MD, PhD, Principal Investigator, Affiliation: Massachusetts General Hospital

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)

Secondary outcome:

Aggregate mean difference in t1/2max between the methods

Aggregate mean difference in Cmax between the methods

Aggregate mean difference in area under the curve (AUC) between methods

AUC of 0-1 hour (and by subtraction hours 1-5)

AUC of 0-2 hours (and by subtraction hours 2-5)

Time to 50% of Total AUC (or said another way, time to 50% exposure)

Fraction of subjects with difference in tmax between the methods of > 25%

Fraction of "dry" injections with no reflux of fluid from the injection site

Difference in mean visual analog pain score between the two methods

Difference in mean visual analog pain score between insulin and glucagon with subcutaneous injection

Difference in mean visual analog pain score between insulin and glucagon with intradermal injection

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Massachusetts General Hospital, Boston, Massachusetts 02114, United States

Starting date: August 2012
Last updated: June 10, 2014