Pharmacology of Insulin Injected With Jet-injection in Diabetes

Radboud University Medical Center

Status and phase

Completed

Phase 4

Conditions

Diabetes Mellitus

Treatments

Device: jet injection device

Study type

Interventional

Funder types

Other

Identifiers

NCT01438632

PKPD_INSJ_2

Details and patient eligibility

About

Full description

A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes (type 1 and type 2) shows the same difference in the pharmacokinetic and pharmacodynamic profile.The pharmacokinetic and pharmacodynamic profile of insulin aspart will be derived from the time-action profiles of insulin and glucose, respectively, in response to insulin injected directly prior to a standardised meal. All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject an individualised dose of insulin and a conventional insulin pen to inject a placebo solution, and on the other occasion insulin will be injected with the conventional pen and placebo with the jet-injector. The order of these occasions will be randomised and blinded to both the investigator and the participating patient. The primary endpoint is the hyperglycaemic burden as reflected by area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion (BG-AUC0-2h). Secondary study endpoints are the area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h (BG-AUC0-6h), maximal glucose excursion (BGmax), time to maximal glucose excursion (T-BGmax), time until plasma glucose has returned to baseline (T-BGBL), maximal insulin concentration (C-INSmax), time to maximal insulin concentration (T-INSmax), area under the insulin concentration curve (INSAUC) and time until 50% of insulin absorption (T-INSAUC50%) after insulin injection and meal ingestion.

Enrollment

24 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Body-mass index 18-32 kg/m2
Stable glycaemic control with HbA1c 6.0-9.0%
Duration of diabetes >1 year
Insulin use at least once daily or with subcutaneous pump
Blood pressure <160/90 mmHg

Exclusion criteria

Inability to provide informed consent
Requirement of <8 units of rapid-acting insulin (analogue) before meals
Chronic use of sulphonylurea derivatives, GLP-1 based treatments, acarbose or thiazolidinediones
Treatment with prednisolone, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents, cytostatic drugs, hormone therapy except insulin, thyroid supplementation and oral anticonceptives
Known allergy to aspart insulin
Symptomatic diabetic neuropathy
History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) in the past 6 months
Pregnancy or the intention to become pregnant