Diabetes Mellitus, Type IPhase 1PK/PDNCT00652288

Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs

A Phase 1 study testing Insulin analogs (Lispro and Aspart), Insulin analogs (Aspart and Detemir) and Insulin analogs (Lispro and Glargine) in people with Diabetes Mellitus, Type I, run by Yale University.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim of this study is to evaluate the variations in pharmacokinetic and pharmacodynamic properties of rapid-acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes. Read more about this study

Who is it for?: Ages 8 to 17 years
Conditions the study is for: Diabetes Mellitus, Type I
What is being tested?: Insulin analogs (Lispro and Aspart), Insulin analogs (Aspart and Detemir) and Insulin analogs (Lispro and Glargine)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: No sites listed yet
Study dates: Apr 2007to Sep 2011
Phase: Phase 1
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 8 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
Diagnosis of T1D for at least one year's duration;
On CSII therapy for at least three months;
HbA1c 6.5-8.0%, inclusive;
Body mass index < 95% for age and gender;
Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects)
Ability to comprehend written and spoken English

Who cannot join

Any other medical disease aside from T1D or treated hypothyroidism
Receiving any other medication besides insulin or levothyroxine
Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
Inability to comprehend written and spoken English
Any other condition, which in the judgement of the investigators, would interfere with the subject's or parents' ability to provide informed consent or the investigator's ability to perform the study

About this study

Official title: Evaluation of Pharmacokinetic and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs Given as a Bolus by Continuous Subcutaneous Insulin Infusion (CSII) and in MDI Basal-Bolus Therapy in Pediatric Subjects With Type 1 Diabetes (TID)

The specific factors under investigation are:

the effects of puberty
type of insulin analog
site of catheter insertion
and age of catheter

Read the detailed description

The aim of this study is to evaluate the variations in pharmacokinetic (as determined by serum free insulin concentrations) and pharmacodynamic (as determined by the glucose infusion rate required to maintain euglycemia during a euglycemic clamp) properties of the rapid acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes. The specific factors we will investigate are the effects of puberty (pre- vs. pubertal), type of insulin analog (lispro or aspart insulin), site of catheter insertion (gluteal vs. abdominal), and age of catheter (fresh insertion vs. three-day duration) Our hypotheses are that the peak (Imax) and area under the curve (IAUC) serum free insulin concentration, and the peak glucose infusion rate required to maintain euglycemia (GIRmax) and area under the curve (GIRAUC) will vary based on these conditions, in children given the same weight-based dose.

We will also evaluate the pharmacokinetic and pharmacodynamic properties of Aspart and Lispro insulin when used in a basal-bolus regimen with insulin Detemir or Glargine, new basal insulin analogs, given as separate injections and when combined in a single injection in adolescent patients with Type 1 DM. We hypothesize that the peak (IMAX) and area under the curve (IAUC) serum insulin concentrations, and the peak glucose infusion rate required to maintain euglycemia (GIRMAX) and area under the curve (GIRAUC) of the Aspart/Lispro bolus, will be similar when the Aspart/Lispro is combined in the same syringe with the insulin Detemir/Glargine, compared to when the Aspart/Lispro and Detemir/Glargine are given as two separate injections.

Conditions: Diabetes Mellitus, Type I
Being tested: Insulin analogs (Lispro and Aspart), Insulin analogs (Aspart and Detemir), Insulin analogs (Lispro and Glargine)
Keywords: Type I Diabetes Mellitus
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Insulin analogs (Lispro and Aspart)Drug
Also called Humalog, Novolog
Insulin bolus given through insulin pump
Insulin analogs (Aspart and Detemir)Drug
Drugs given separately
Insulin analogs (Aspart and Detemir)Drug
Drugs given in the same injection
Insulin analogs (Lispro and Glargine)Drug
Drugs given separately
Insulin analogs (Lispro and Glargine)Drug
Drugs given in single injection

Study groups in NCT00652288
Study group	Role	What they receive
Catheter day 4	Active comparator	Adolescents with type 1 diabetes with catheters day #4 Receives: Drug: Insulin analogs (Lispro and Aspart)
Catheter day 1	Active comparator	Adolescents with type 1 diabetes with catheter day #1 Receives: Drug: Insulin analogs (Lispro and Aspart)
Aspart and Detemir	Active comparator	Adolescents with type 1 diabetes Receives: Drug: Insulin analogs (Aspart and Detemir)
Lispro and Glargine	Active comparator	Adolescents with type 1 diabetes Receives: Drug: Insulin analogs (Lispro and Glargine)

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
Measured: Six hour observation period

Secondary outcomes (1)

Time to Maximum Glucose Infusion Rate
Measured: Six Hour Observation period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2007Sep 2011

First posted3 Apr 2008 (estimated)
Study startApr 2007
Primary completionSep 2011
Study completionSep 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type IStudies of the same condition, open and under way.
More trials run by Yale UniversityThe 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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00652288
Sponsor's protocol ID: 403026582
Other IDs: JDRF Hypoglycemia Grant
Acronym: PK/PD
Status last verified: Aug 2016
First submitted: 27 Mar 2008
Last updated: 1 Sep 2016
Results posted: No
Data monitoring committee: No

Publications

Cengiz E, Swan KL, Tamborlane WV, Sherr JL, Martin M, Weinzimer SA. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin. Diabetes Care. 2012 Apr;35(4):690-2. doi: 10.2337/dc11-0732. Epub 2012 Feb 28.
PubMed 22374642
Cengiz E, Tamborlane WV, Martin-Fredericksen M, Dziura J, Weinzimer SA. Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine insulin: results of glucose clamp studies in youth with type 1 diabetes. Diabetes Care. 2010 May;33(5):1009-12. doi: 10.2337/dc09-2118. Epub 2010 Feb 11.
PubMed 20150302
Swan KL, Dziura JD, Steil GM, Voskanyan GR, Sikes KA, Steffen AT, Martin ML, Tamborlane WV, Weinzimer SA. Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy. Diabetes Care. 2009 Feb;32(2):240-4. doi: 10.2337/dc08-0595. Epub 2008 Nov 18.
PubMed 19017777
Swan KL, Weinzimer SA, Dziura JD, Steil GM, Voskanyan GR, Steffen AT, Martin ML, Tamborlane WV. Effect of puberty on the pharmacodynamic and pharmacokinetic properties of insulin pump therapy in youth with type 1 diabetes. Diabetes Care. 2008 Jan;31(1):44-6. doi: 10.2337/dc07-0737. Epub 2007 Oct 1. No abstract available.
PubMed 17909083

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Diabetes Mellitus, Type I trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of Pharmacokinetic and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs Given as a Bolus by Continuous Subcutaneous Insulin Infusion (CSII) and in MDI Basal-Bolus Therapy in Pediatric Subjects With Type 1 Diabetes (TID)
ClinicalTrials.gov ID: NCT00652288
Acronym / sponsor ID: PK/PD / 403026582
Conditions: Diabetes Mellitus, Type I
Keywords: Type I Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Study start: Apr 2007
Primary completion: Sep 2011 (actual)
Study completion: Sep 2011 (actual)
First posted: 3 Apr 2008 (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.

The specific factors under investigation are:

the effects of puberty
type of insulin analog
site of catheter insertion
and age of catheter

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Catheter day 4	Active comparator	Drug: Insulin analogs (Lispro and Aspart)Adolescents with type 1 diabetes with catheters day #4
Catheter day 1	Active comparator	Drug: Insulin analogs (Lispro and Aspart)Adolescents with type 1 diabetes with catheter day #1
Aspart and Detemir	Active comparator	Drug: Insulin analogs (Aspart and Detemir)Adolescents with type 1 diabetes
Lispro and Glargine	Active comparator	Drug: Insulin analogs (Lispro and Glargine)Adolescents with type 1 diabetes

Who may qualify

Ages: 8 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
Diagnosis of T1D for at least one year's duration;
On CSII therapy for at least three months;
HbA1c 6.5-8.0%, inclusive;

Key exclusion criteria (5 listed)

Any other medical disease aside from T1D or treated hypothyroidism
Receiving any other medication besides insulin or levothyroxine
Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
Inability to comprehend written and spoken English
Any other condition, which in the judgement of the investigators, would interfere with the subject's or parents' ability to provide informed consent or the investigator's ability to perform the study

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
Insulin analogs (Lispro and Aspart)Also: Humalog, NovologInsulin bolus given through insulin pump	Drug	Catheter day 1, Catheter day 4
Insulin analogs (Aspart and Detemir)Drugs given separately	Drug	Aspart and Detemir
Insulin analogs (Aspart and Detemir)Drugs given in the same injection	Drug	Aspart and Detemir
Insulin analogs (Lispro and Glargine)Drugs given separately	Drug	Lispro and Glargine
Insulin analogs (Lispro and Glargine)Drugs given in single injection	Drug	Lispro and Glargine

Primary outcome

Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
Time frame: Six hour observation period

1 secondary outcome

Time to Maximum Glucose Infusion Rate
Time frame: Six Hour Observation period

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 1 Sep 2016.
Results publication: PubMed 22374642Cengiz E, Swan KL, Tamborlane WV, Sherr JL, Martin M, Weinzimer SA. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin. Diabetes Care. 2012 Apr;35(4):690-2. doi: 10.2337/dc11-0732. Epub 2012 Feb 28.
Results publication: PubMed 20150302Cengiz E, Tamborlane WV, Martin-Fredericksen M, Dziura J, Weinzimer SA. Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine insulin: results of glucose clamp studies in youth with type 1 diabetes. Diabetes Care. 2010 May;33(5):1009-12. doi: 10.2337/dc09-2118. Epub 2010 Feb 11.
Results publication: PubMed 19017777Swan KL, Dziura JD, Steil GM, Voskanyan GR, Sikes KA, Steffen AT, Martin ML, Tamborlane WV, Weinzimer SA. Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy. Diabetes Care. 2009 Feb;32(2):240-4. doi: 10.2337/dc08-0595. Epub 2008 Nov 18.
Results publication: PubMed 17909083Swan KL, Weinzimer SA, Dziura JD, Steil GM, Voskanyan GR, Steffen AT, Martin ML, Tamborlane WV. Effect of puberty on the pharmacodynamic and pharmacokinetic properties of insulin pump therapy in youth with type 1 diabetes. Diabetes Care. 2008 Jan;31(1):44-6. doi: 10.2337/dc07-0737. Epub 2007 Oct 1. No abstract available.

Related trials for Diabetes Mellitus, Type I

RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
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Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
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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.

Stuart A Weinzimer, MD principal investigator

Yale University

Eda Cengiz, MD principal investigator

Yale University

Questions about this trial

What is this clinical trial studying?

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 8 inclusion and 5 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 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Maximum Glucose Infusion Rate (GIR) to maintain euglycemia (time frame: Six hour observation period). 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 NCT00652288, which also lists 4 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 1 Sep 2016.