Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intradermal injection
Subcutaneous injection
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring intradermal, pharmacokinetics, microneedle, insulin, glucagon
Eligibility 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
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Intradermal first
Subcutaneous first
Arm Description
Intradermal injection experiment first, followed by subcutaneous injection experiment
Subcutaneous injection experiment first, followed by intradermal injection experiment
Outcomes
Primary Outcome Measures
Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)
Secondary Outcome Measures
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
Full Information
NCT ID
NCT01684956
First Posted
August 23, 2012
Last Updated
September 6, 2016
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01684956
Brief Title
Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Type 1 Diabetes
Official Title
Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Volunteers With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
December 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
intradermal, pharmacokinetics, microneedle, insulin, glucagon
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intradermal first
Arm Type
Experimental
Arm Description
Intradermal injection experiment first, followed by subcutaneous injection experiment
Arm Title
Subcutaneous first
Arm Type
Experimental
Arm Description
Subcutaneous injection experiment first, followed by intradermal injection experiment
Intervention Type
Procedure
Intervention Name(s)
Intradermal injection
Intervention Type
Procedure
Intervention Name(s)
Subcutaneous injection
Primary Outcome Measure Information:
Title
Aggregate mean difference in tmax between the delivery methods (the insulin and glucagon data will be evaluated separately)
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Aggregate mean difference in t1/2max between the methods
Time Frame
1 day visit
Title
Aggregate mean difference in Cmax between the methods
Time Frame
1 day
Title
Aggregate mean difference in area under the curve (AUC) between methods
Time Frame
1 day
Title
AUC of 0-1 hour (and by subtraction hours 1-5)
Time Frame
1 day
Title
AUC of 0-2 hours (and by subtraction hours 2-5)
Time Frame
1 day
Title
Time to 50% of Total AUC (or said another way, time to 50% exposure)
Time Frame
1 day
Title
Fraction of subjects with difference in tmax between the methods of > 25%
Time Frame
1 day
Title
Fraction of "dry" injections with no reflux of fluid from the injection site
Time Frame
1 day
Title
Difference in mean visual analog pain score between the two methods
Time Frame
1 day
Title
Difference in mean visual analog pain score between insulin and glucagon with subcutaneous injection
Time Frame
1 day
Title
Difference in mean visual analog pain score between insulin and glucagon with intradermal injection
Time Frame
1 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Russell, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetic Comparison of Intradermal Versus Sub-cutaneous Insulin and Glucagon Delivery in Type 1 Diabetes
We'll reach out to this number within 24 hrs