Insulin by Jet-injection for Hyperglycemia in Diabetes

Diabetes Mellitus Clinical Trial

Official title:

The Effect of Rapid-acting Insulin Injected by Needle-free Jet-injection in the Management of Hyperglycemia in Patients With Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01947556
• Other study ID #: PKPD_INSJ_3
• Status: Completed
• Phase: N/A
• First received: September 2, 2013
• Last updated: November 25, 2014
• Start date: March 2014
• Est. completion date: November 2014

Study information

• Verified date: November 2014
• Source: University Medical Center Nijmegen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Hyperglycemia

Intervention

Drug:
• insulin aspart
After hyperglycaemia (18-23 mmol/l) has been reached (by decreasing or interrupting exogenous insulin administration 12-24 hours before the experiment), aspart 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) will be administered subcutaneously by Insujet pen or conventional insulin pen, on two separate occasions, or vice versa. The injection will be given by the subject under supervision of the research staff.

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Nijmegen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	NRS pain	The amount of discomfort or pain and the ease of use experienced with the two administration methods using a numeric rating scale from 0 to 10 (will be administered 30 minutes after insulin administration)	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Other	hypoglycaemia	Number of patients requiring exogenous glucose infusion to prevent hypoglycaemia (blood glucose =3.9 mmol/l) after insulin injection;	participants will be followed for the duration of the study, an expected average of 4 weeks	Yes
Other	exogenous glucose	Amount of exogenous glucose required to prevent hypoglycaemia after insulin injection	participants will be followed for the duration of the study, an expected average of 4 weeks	Yes
Other	time exogenous glucose requirement	Duration of time that exogenous glucose is required to prevent hypoglycaemia after insulin injection.	participants will be followed for the duration of the study, an expected average of 4 weeks	Yes
Primary	T-BG=10	the time in minutes until plasma glucose concentration has dropped with = 10mmol/l (T-BG=10).	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	T-BG5 and 8 (min)	the time in minutes until plasma glucose values drop below 8 an 5 mmol/l, respectively	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	Rfall	the slope of the glucose fall (mmol • l-1 • min-1), calculated from the time- glucose curve	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	BG-AUC 0-2h	the area under the time-glucose curve, reflecting post-injection hyperglycaemic burden, from 0 to 2h after insulin injection.	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	BG-AUC 0-6h	the area under the time-glucose curve (mmol • min-1 • l-1), from 0 to 6h after insulin injection.	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	C-INSmax (pmol/l)	maximal insulin concentration	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	T-INSmax	time to maximal insulin concentration in minutes(C-INSmax)	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	T-INSBL	the time until plasma insulin values drop below baseline values (minutes)	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	INSAUC	area under the insulin concentration curve (pmol • min-1 • l-1)(from timepoint 0), reflects total insulin absorption	participants will be followed for the duration of the study, an expected average of 4 weeks	No
Secondary	T-INSAUC50%	time until 50% of insulin absorption in minutes(mean residence time, MRT)	participants will be followed for the duration of the study, an expected average of 4 weeks	No