Clinical trial NCT01947556: Insulin by Jet-injection for Hyperglycemia in Diabetes
Official title: The Effect of Rapid-acting Insulin Injected by Needle-free Jet-injection in the Management of Hyperglycemia in Patients With Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Keywords: diabetes
insulin administration
hyperglycaemia
insulin aspart
Lead sponsor: University Medical Center Nijmegen
Sponsor class: OTHER
First posted: 2013-09-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the pharmacokinetic and pharmacodynamic profile of the rapid-acting insulin analogue aspart (Novorapid®) injected subcutaneously by jet-injection to that of the same insulin injected with a conventional pen in the management of hyperglycemia in subjects with diabetes

Detailed description: Recently, we showed in both healthy, non-diabetic volunteers and in patients with type 1 (T1DM) and insulin-treated type 2 diabetes (T2DM) a 40-50% faster absorption of rapid-acting insulin analogues when administered by jet injection technology rather than by conventional insulin pen. The faster insulin action of insulin administration by jet injection may be especially advantageous for correction of hyperglycemia.

To investigate this, a open-label randomised controlled cross-over study will be performed in 20 adult patients (18-75 years) with T1DM or T2DM on basal-bolus insulin treatment.

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 (in a dose of 1.5 times the amount of insulin needed to reduce blood glucose to 6 mmol/l calculated by the insulin-sensitivity factor) after reaching hyperglycemia (18-23 mmol/l). All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject insulin, and on the other occasion insulin will be injected with a conventional insulin pen. The order of these occasions will be randomised. Both devices will be operated by the patient after sufficient training. Ease of use will be evaluated.

Eligibility criteria: Inclusion Criteria:

* diabetes mellitus type 1 or 2
* Age 18-75 years
* Body-Mass Index ≥25 kg/m2 and ≤40 kg/m2
* Stable glycaemic control with HbA1c ≥48 (6.5%) and ≤86 mmol/mol (10%)
* Insulin treatment according to basal-bolus regimen, i.e. by multiple daily injections at least four times daily, or by subcutaneous insulin pump, for at least 12 months, use of metformin allowed

Exclusion Criteria:

* Inability to provide informed consent
* Insulin requirement of \<34 or \>200 units per day
* Treatment with systemic corticosteroids, immunosuppressive or cytostatic drugs
* Known allergy to aspart insulin
* Use of oral antidiabetic drugs other than metformin
* 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 previous 6 months
* Pregnancy or the intention to become pregnant
* Renal disease (creatinine \>150 μmol/l or MDRD-GFR \<30 ml/min/1.73m2)
* Liver disease (aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range)
* Presence of any other medical condition that might interfere with the study protocol
* anemia

Primary outcomes:
measure: T-BG≥10
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
Secondary outcomes:
measure: T-BG5 and 8 (min)
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: Rfall
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: BG-AUC 0-2h
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: BG-AUC 0-6h
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: C-INSmax (pmol/l)
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: T-INSmax
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: T-INSBL
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: INSAUC
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: T-INSAUC50%
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
Other outcomes:
measure: NRS pain
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: hypoglycaemia
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: exogenous glucose
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
measure: time exogenous glucose requirement
timeFrame: participants will be followed for the duration of the study, an expected average of 4 weeks
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Bastiaan de Galan, MD PhD
role: STUDY_CHAIR
References: