Diabetes MellitusPhase 4NCT01438632
Pharmacology of Insulin Injected With Jet-injection in Diabetes
A Phase 4 study testing jet injection device in people with Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- jet injection device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2011to Jul 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500 HB
About this study
Official title: Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes
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 shows the same difference in the pharmacokinetic and pharmacodynamic profile.
Read the detailed 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.
- Conditions
- Diabetes Mellitus
- Being tested
- jet injection device
- Keywords
- Insulin action, Jet injector, Diabetes Mellitus, Pharmacodynamics, Pharmacokinetics, Insulin analogs, Insulin aspart
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
jet injection deviceDevice
Also called Jet injector: InsuJet™ from the European Pharma Group, Insulin device: NovoPen® 3 from Novo Nordisk
Rapid-acting insulin analogue aspart (Novorapid®) administration by means of a jet injector or a conventional insulin pen in the subcutaneous tissue. Dosage of insulin will be determined by the normal dosage of insulin used by the patient before breakfast.
| Study group | Role | What they receive |
|---|---|---|
| jet injector | Experimental | Jet injectors deliver insulin at a high velocity (typically >100m/s) across the skin in the subcutaneous tissue, without the use of a needle Receives: Device: jet injection device |
| conventional insulin pen | Active comparator | Not described Receives: Device: jet injection device |
What is being measured
The primary outcome is the main question the study is designed to answer.
BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion.
based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration
Measured: 2 days (2 hours per day)
Secondary outcomes (11)
BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion
Maximal plasma glucose value after the standardised meal
Measured: 2 days (6 hours each day)
T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion
Time until maximal glucose value after the standardised meal and insulin injection
Measured: 2 days (6 hours per day)
BG-AUC0-6h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h after insulin injection and meal ingestion
Based on glucose concentration measurements for the total 6 hours of the study
Measured: 2 days (6 hours each day)
T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion
based on glucose level measurements during the total 6 hours of the study
Measured: 2 days (6 hours per day)
T-INSmax (min): time to maximal insulin concentration (C-INSmax)
Maximal insulin concentration after insulin injection
Measured: 2 days (6 hours per day)
INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0)
Based on insulin concentration measurements during the total 6 hours of the study
Measured: 2 days (6 hours per day)
T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT)
Based on insulin concentration measurements during the total 6 hours of the study
Measured: 2 days (6 hours each day)
Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
This will be assessed for the individual patient after every test. After completion of the experiments all cases of hypoglycemia will be assessed
Measured: 2 days
Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
This will be assessed for the individual patient after every test. After completion of the experiments the total amount of glucose infused will be calculate for each device
Measured: 2 days
Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
This will be assessed for the individual patient after every test. After completion of the experiments the total amount of time will be calculate for each device
Measured: 2 days
BG-AUC0-1h
the area under the baseline-subtracted plasma glucose concentration time-curve during the first hour
Measured: 2 days (6 hours per day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionMay 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Pharma Group (EPG)
- Responsible party
- Sponsor
- Investigators
- Bastiaan E de Galan, MD, PhD, Study director, Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section DiabetesElsemiek EC Engwerda, BSc, Principal investigator, Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01438632
- Sponsor's protocol ID
- PKPD_INSJ_2
- Status last verified
- Aug 2011
- First submitted
- 19 Sep 2011
- Last updated
- 12 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006 Jul;5(7):543-8. doi: 10.1038/nrd2076.
PubMed 16816837Rave K, Klein O, Frick AD, Becker RH. Advantage of premeal-injected insulin glulisine compared with regular human insulin in subjects with type 1 diabetes. Diabetes Care. 2006 Aug;29(8):1812-7. doi: 10.2337/dc06-0383.
PubMed 16873785Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care. 2011 Aug;34(8):1804-8. doi: 10.2337/dc11-0182. Epub 2011 Jun 29.
PubMed 21715522
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes
- ClinicalTrials.gov ID
- NCT01438632
- Acronym / sponsor ID
- PKPD_INSJ_2
- Conditions
- Diabetes Mellitus
- Keywords
- Insulin action, Jet injector, Diabetes Mellitus, Pharmacodynamics, Pharmacokinetics, Insulin analogs, Insulin aspart
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- European Pharma Group (EPG)
- Study start
- Sep 2011
- Primary completion
- May 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 22 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 shows the same difference in the pharmacokinetic and pharmacodynamic profile.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| jet injector | Experimental | Device: jet injection deviceJet injectors deliver insulin at a high velocity (typically >100m/s) across the skin in the subcutaneous tissue, without the use of a needle |
| conventional insulin pen | Active comparator | Device: jet injection device |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| jet injection deviceAlso: Jet injector: InsuJet™ from the European Pharma Group, Insulin device: NovoPen® 3 from Novo NordiskRapid-acting insulin analogue aspart (Novorapid®) administration by means of a jet injector or a conventional insulin pen in the subcutaneous tissue. Dosage of insulin will be determined by the normal dosage of insulin used by the patient before breakfast. | Device | conventional insulin pen, jet injector |
Primary outcome
BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion.
Time frame: 2 days (2 hours per day)
based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration
11 secondary outcomes
BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion
Time frame: 2 days (6 hours each day)
T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion
Time frame: 2 days (6 hours per day)
BG-AUC0-6h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h after insulin injection and meal ingestion
Time frame: 2 days (6 hours each day)
T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion
Time frame: 2 days (6 hours per day)
T-INSmax (min): time to maximal insulin concentration (C-INSmax)
Time frame: 2 days (6 hours per day)
INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0)
Time frame: 2 days (6 hours per day)
T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT)
Time frame: 2 days (6 hours each day)
Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
Time frame: 2 days
Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
Time frame: 2 days
Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
Time frame: 2 days
BG-AUC0-1h
Time frame: 2 days (6 hours per day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2013.
- Background: PubMed 16816837Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006 Jul;5(7):543-8. doi: 10.1038/nrd2076.
- Background: PubMed 16873785Rave K, Klein O, Frick AD, Becker RH. Advantage of premeal-injected insulin glulisine compared with regular human insulin in subjects with type 1 diabetes. Diabetes Care. 2006 Aug;29(8):1812-7. doi: 10.2337/dc06-0383.
- Background: PubMed 21715522Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care. 2011 Aug;34(8):1804-8. doi: 10.2337/dc11-0182. Epub 2011 Jun 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bastiaan E de Galan, MD, PhD study director
Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section Diabetes
Elsemiek EC Engwerda, BSc principal investigator
Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing jet injection device in people with Diabetes Mellitus, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion. (time frame: 2 days (2 hours per day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01438632, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2013.