DiabetesNCT00469833

Insulin Secretion in Diabetes Before and After Glycemic Control

A study testing insulin glargine in people with Diabetes and Hyperglycemia, run by US Department of Veterans Affairs at 1 site in United States.

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

Who is it for?: Ages 30 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Diabetes, Hyperglycemia
What is being tested?: insulin glargine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteUnited States
Study dates: Apr 2008to Sep 2012
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 30 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Aim 1:
(non-diabetics)
male/female 30-65 yrs old,
free of active medical disease,
no history of diabetes.
(diabetics)

Show all 11Show fewer

HbA1c=6.5-8.5,
treated with metformin, a sulfonylurea, or combination,
Stable body wt with BMI 28-40.
Aim 2: Same as above
Aim 3: Diabetic with HgA1c 8.0-9.5

Who cannot join

Aim 1: For both groups: no history of: pancreatitis, cardiac, gastrointestinal, renal or liver disease.
Aim 2: Same as above
Aim 3: Same as above, plus a diagnosis of incipient diabetic nephropathy severe nonproliferative, or proliferative retinopathy.

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Medical Center, Cincinnati
Cincinnati, Ohio, 45220

Other trials in United States

About this study

Official title: Pathogenesis of the Impaired Incretin Effect in Type 2 Diabetes

The objective of this project is to understand defects in insulin secretion that contribute to abnormal glucose metabolism in patients with diabetes. In particular the effects of signals released from the intestine to stimulate insulin secretion will be tested. Patients with type 2 diabetes will have insulin secretion in response to glucose and intestinal factors before and after insulin treatment to lower their blood glucose. It is expected that the results of this work will provide valuable information for treating diabetic people.

Read the detailed description

The objective of this project is to understand defects in insulin secretion that contribute to abnormal glucose metabolism in patients with diabetes. Diabetes is a major problem for patients receiving care at VA medical centers among whom 20% are affected. Specifically, this project will seek to determine the mechanism(s) by which the incretin effect is impaired in diabetic patients. The incretin effect refers to the action of GI hormones and neural stimuli to increase insulin secretion after food intake, and accounts for approximately 50% of postprandial insulin secretion in nondiabetic humans. There are several studies indicating that this response is severely impaired in patients with type 2 diabetes. The mechanism(s) by which this occurs has not been explained. There is some evidence to suggest that secretion of the important incretins, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), may be impaired in diabetic individuals. There is also some data to suggest that the beta-cells in persons with diabetes are insensitive to the incretins. The problem with the current state of knowledge in this area is that previous work has involved small numbers of diabetic subjects, and did not directly test mechanisms by which the incretin effect is altered in diabetes.

In this project we will determine the role of hyperglycemia to impair the incretin effect. Type 2 diabetic subjects will have the incretin effect measured before and after intensified diabetes treatment. This study will test the effect of chronic hyperglycemia on incretin mediated insulin secretion. In all studies, the incretin effect will be measured before and after these interventions using studies with a within subjects design. A combined glucose clamp/meal tolerance test protocol will be used to quantify the incretin effect.

These studies will allow the role of incretin secretion, incretin action, and overall metabolic milieu, on postprandial insulin secretion to be defined. The results of these studies will add important new information for understanding abnormal beta-cell function in diabetes. By identifying the sites where the incretin effect is impaired this project will provide the basis for new approaches to treat diabetic patients. This is especially relevant with the recent availability of new medications that target the incretin pathways to lower blood glucose.

The blood samples will be drawn and processed in the GCRC. The samples will be frozen and stored in Building 15, Room 401. Samples will be shipped to the Genome Research Institute by staff trained in IATA shipping procedures.

Conditions: Diabetes, Hyperglycemia
Being tested: insulin glargine
Keywords: Diabetes, Glucose Tolerance, Incretin, Insulin
Medical subject headings: Diabetes Mellitus, Hyperglycemia, Insulin Resistance

What participants receive

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

insulin glargineDrug
Also called Basal insulin, Long-acting insulin, Lantus
Diabetic subjects will be treated with insulin glargine once daily for 2 months. Subjects will monitor their blood glucose and have their insulin dose adjusted in steps of 4-6 units to achieve a goal of less than or equal to 120 mg/dl for fasting blood glucose.

Study groups in NCT00469833
Study group	Role	What they receive
Arm 1	Experimental	Intervention: Insulin glargine treatment. The study is designed as a within subjects comparison of insulin secretion in type 2 diabetic patients before and after 2 months of insulin treatment to reduce blood glucose. Insulin secretion will be determined with a hyperglycemic clamp using 20% dextrose, and ingestion of an oral glucose solution (75 g). Receives: Drug: insulin glargine

What is being measured

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

ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.
Measured: 180 minutes
C-peptide Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.
Measured: 180 minutes
Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.
Measured: 180 minutes

Secondary outcomes (1)

HbA1c Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Type 2 diabetic subjects had HbA1c measured before and after 2 months of basal insulin glargine treatment.
Measured: 2 months

Timeline

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

Apr 2008Sep 2012

First posted7 May 2007 (estimated)
Study startApr 2008
Primary completionDec 2011
Study completionSep 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
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 N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00469833
Sponsor's protocol ID: ENDA-010-06S
Status last verified: Jan 2015
First submitted: 4 May 2007
Last updated: 15 Jan 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

An Z, Prigeon RL, D'Alessio DA. Improved glycemic control enhances the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2013 Dec;98(12):4702-8. doi: 10.1210/jc.2013-1199. Epub 2013 Oct 3.
PubMed 24092826

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?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pathogenesis of the Impaired Incretin Effect in Type 2 Diabetes
ClinicalTrials.gov ID: NCT00469833
Acronym / sponsor ID: ENDA-010-06S
Conditions: Diabetes, Hyperglycemia
Keywords: Diabetes, Glucose Tolerance, Incretin, Insulin
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: US Department of Veterans AffairsUS federal agency
Study start: Apr 2008
Primary completion: Dec 2011 (actual)
Study completion: Sep 2012 (actual)
First posted: 7 May 2007 (estimated)
Results: Posted 15 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Arm 1	Experimental	Drug: insulin glargineIntervention: Insulin glargine treatment. The study is designed as a within subjects comparison of insulin secretion in type 2 diabetic patients before and after 2 months of insulin treatment to reduce blood glucose. Insulin secretion will be determined with a hyperglycemic clamp using 20% dextrose, and ingestion of an oral glucose solution (75 g).

Who may qualify

Ages: 30 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Aim 1:
Aim 2: Same as above
Aim 3: Diabetic with HgA1c 8.0-9.5

Key exclusion criteria (3 listed)

Aim 1: For both groups: no history of: pancreatitis, cardiac, gastrointestinal, renal or liver disease.
Aim 2: Same as above
Aim 3: Same as above, plus a diagnosis of incipient diabetic nephropathy severe nonproliferative, or proliferative retinopathy.

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 glargineAlso: Basal insulin, Long-acting insulin, LantusDiabetic subjects will be treated with insulin glargine once daily for 2 months. Subjects will monitor their blood glucose and have their insulin dose adjusted in steps of 4-6 units to achieve a goal of less than or equal to 120 mg/dl for fasting blood glucose.	Drug	Arm 1

Primary outcome

ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Time frame: 180 minutes
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.
C-peptide Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Time frame: 180 minutes
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.
Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Time frame: 180 minutes
Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.

1 secondary outcome

HbA1c Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.
Time frame: 2 months

Results and safety

Results posted to the registry on 15 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Uncontrolled Type 2 Diabetic Subjects	17	15

Primary outcome: ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

Time frame: 180 minutes. Mean (Standard Error). Unit: pmol/min

Measure	Oral Glucose n = 15	IV Glucose n = 15
Insulin secretion at baseline	0.67 (0.07)	0.75 (0.10)
Insulin secretion at 8 weeks	1.11 (0.22)	0.76 (0.11)

Primary outcome: C-peptide Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

Time frame: 180 minutes. Mean (Standard Error). Unit: nmol/L

Measure	Oral Glucose n = 15	IV Glucose n = 15
C-peptide at baseline	7.10 (0.92)	5.63 (0.97)
C-peptide at 8 weeks	10.89 (2.20)	6.02 (0.88)

Primary outcome: Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

Time frame: 180 minutes. Mean (Standard Error). Unit: pmol/L

Measure	Oral Glucose n = 15	IV Glucose n = 15
Insulin at baseline	546.9 (162.6)	316.4 (59.0)
Insulin at 8 weeks	934.6 (282.2)	395.6 (106.3)

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1	0 of 15 (0%)	0 of 15 (0%)	Not reported

Limitations and caveats (from the sponsor): Two subjects could not complete the initial assessment due to poor IV access. All 15 subjects who completed the initial assessment and were started on insulin completed the study. There were no significant adverse events.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24092826An Z, Prigeon RL, D'Alessio DA. Improved glycemic control enhances the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2013 Dec;98(12):4702-8. doi: 10.1210/jc.2013-1199. Epub 2013 Oct 3.

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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.

David D'Alessio, MD principal investigator

Cincinnati VA Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing insulin glargine in people with Diabetes and Hyperglycemia, run by US Department of Veterans Affairs at 1 site in United States.

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 11 inclusion and 3 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 15 Jan 2015. 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 United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. (time frame: 180 minutes). The study lists 3 primary outcomes in all. 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 NCT00469833, which also lists 1 linked publication.

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 15 Jan 2015.