Diabetes Mellitus, Type 1BPK003NCT00943787
Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus
A study testing Hyperinsulinemic, euglycemic and hypoglycemic clamp in people with Diabetes Mellitus, Type 1, run by University of Virginia at 1 site in United States.
Trial summary
The researchers plan to test the following hypothesis: A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Hyperinsulinemic, euglycemic and hypoglycemic clamp
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to May 2009
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participated in and satisfied all of the inclusion criteria of NCT00315939
- 18 years of age or older
- Have Type 1 Diabetes Mellitus defined by American Diabetes Association criteria or judgment of physician
- Since our major goal is the investigation of hypoglycemia, we will preferentially recruit patients with a history of severe hypoglycemia/moderate hypoglycemia anticipating that approximately (~) half of the recruited subjects will have had two or more severe or moderate hypoglycemia episodes in the past 12 months
Who cannot join
- Age < 18
- Pregnancy
- Use of oral steroids
- Hematocrit < 36% (females); < 38% (males)
- Symptomatic heart disease (e.g., history of myocardial infarction, history of coronary bypass or stenting procedure, angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages > 50%)
- History of an ischemic cerebrovascular event
Show all 10Show fewer
- Active substance abuse
- Psychosis
- Mental retardation
- Severe depression
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System - Behavioral Medicine Center
Charlottesville, Virginia, 22908
About this study
Official title: Counter-regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus
The researchers plan to test the following hypothesis:
A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body:
- the transport of insulin through small blood vessels: suggesting that hypoglycemia leads to increased insulin sensitivity which then causes recurrent hypoglycemia;
- the endocrine level, defined as insulin-glucose interaction and hormonal counter-regulation.
The researchers plan to investigate the relationships between hypoglycemia, insulin transport, and counter-regulation. This study will ultimately lead to a better understanding of risk for recurrent hypoglycemia.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Hyperinsulinemic, euglycemic and hypoglycemic clamp
- 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.
Hyperinsulinemic, euglycemic and hypoglycemic clampProcedure or surgery
At 21:30h, an overnight insulin infusion was titrated to control the subjects' BG overnight between 100 and 150mg/dL by blood sampling for plasma glucose via a YSI analyzer every 30min and adjusting the rate of insulin infusion as needed. At the beginning of the clamp, the overnight insulin was replaced by an insulin infusion via a Harvard pump given as a 20mU/kg priming over a 10-min period, followed by a constant rate delivery of 1mU/kg/min until the end of the clamp. Blood was sampled for plasma glucose, and glucose was clamped at basal levels for the euglycemic control period of 150min via a variable-rate infusion of 20% dextrose. Then the glucose concentration was lowered at a rate of 1mg/dL/min to a minimum of 50mg/dL, where it was held constant for 30min. Finally, the glucose concentration was increased at a rate of 1mg/dL/min to 90mg/dL, where it was held for an additional 30min. Blood was sampled for epinephrine during euglycemia, hypoglycemia, and recovery.
| Study group | Role | What they receive |
|---|---|---|
| SMBG followed by clamp | Other | One month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia. Receives: Procedure: Hyperinsulinemic, euglycemic and hypoglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Epinephrine Response (LBGI Groups)
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.
Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI < 2.5; Moderate Risk, 2.5 < LBGI < 5; and High Risk, LBGI > 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.
Measured: 285 min (time of clamp)
Secondary outcomes (1)
Maximum Epinephrine Response (ADRR Groups)
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.
Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia.
Low Risk, ADRR < 20; Moderate Risk, 20 < ADRR < 40; and High Risk,ADRR > 40.
Measured: 285 min (time of clamp)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2009 (estimated)
- Study startJan 2006
- Primary completionMay 2009
- Study completionMay 2009
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 (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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 N/A
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Boris Kovatchev, PhD, University of Virginia
- Investigators
- Boris Kovatchev, Ph.D., Principal investigator, University of Virginia Health Systems - Behavioral Medicine Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00943787
- Sponsor's protocol ID
- 12252
- Acronym
- BPK003
- Status last verified
- Aug 2014
- First submitted
- 24 Jun 2009
- Last updated
- 8 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Pitsillides AN, Anderson SM, Kovatchev B. Hypoglycemia risk and glucose variability indices derived from routine self-monitoring of blood glucose are related to laboratory measures of insulin sensitivity and epinephrine counterregulation. Diabetes Technol Ther. 2011 Jan;13(1):11-7. doi: 10.1089/dia.2010.0103.
PubMed 21175266Chan A, Barrett EJ, Anderson SM, Kovatchev BP, Breton MD. Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus. Diabetologia. 2012 Mar;55(3):729-36. doi: 10.1007/s00125-011-2402-3. Epub 2011 Dec 14.
PubMed 22167126
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Counter-regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00943787
- Acronym / sponsor ID
- BPK003 / 12252
- Conditions
- Diabetes Mellitus, Type 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 22 Jul 2009 (estimated)
- Results
- Posted 8 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The researchers plan to test the following hypothesis:
A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body:
- the transport of insulin through small blood vessels: suggesting that hypoglycemia leads to increased insulin sensitivity which then causes recurrent hypoglycemia;
- the endocrine level, defined as insulin-glucose interaction and hormonal counter-regulation.
The researchers plan to investigate the relationships between hypoglycemia, insulin transport, and counter-regulation. This study will ultimately lead to a better understanding of risk for recurrent hypoglycemia.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SMBG followed by clamp | Other | Procedure: Hyperinsulinemic, euglycemic and hypoglycemic clampOne month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participated in and satisfied all of the inclusion criteria of NCT00315939
- 18 years of age or older
- Have Type 1 Diabetes Mellitus defined by American Diabetes Association criteria or judgment of physician
- Since our major goal is the investigation of hypoglycemia, we will preferentially recruit patients with a history of severe hypoglycemia/moderate hypoglycemia anticipating that approximately (~) half of the recruited subjects will have had two or more severe or moderate hypoglycemia episodes in the past 12 months
Key exclusion criteria (10 listed)
- Age < 18
- Pregnancy
- Use of oral steroids
- Hematocrit < 36% (females); < 38% (males)
- Symptomatic heart disease (e.g., history of myocardial infarction, history of coronary bypass or stenting procedure, angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages > 50%)
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 |
|---|---|---|
| Hyperinsulinemic, euglycemic and hypoglycemic clampAt 21:30h, an overnight insulin infusion was titrated to control the subjects' BG overnight between 100 and 150mg/dL by blood sampling for plasma glucose via a YSI analyzer every 30min and adjusting the rate of insulin infusion as needed. At the beginning of the clamp, the overnight insulin was replaced by an insulin infusion via a Harvard pump given as a 20mU/kg priming over a 10-min period, followed by a constant rate delivery of 1mU/kg/min until the end of the clamp. Blood was sampled for plasma glucose, and glucose was clamped at basal levels for the euglycemic control period of 150min via a variable-rate infusion of 20% dextrose. Then the glucose concentration was lowered at a rate of 1mg/dL/min to a minimum of 50mg/dL, where it was held constant for 30min. Finally, the glucose concentration was increased at a rate of 1mg/dL/min to 90mg/dL, where it was held for an additional 30min. Blood was sampled for epinephrine during euglycemia, hypoglycemia, and recovery. | Procedure or surgery | SMBG followed by clamp |
Primary outcome
Maximum Epinephrine Response (LBGI Groups)
Time frame: 285 min (time of clamp)
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI < 2.5; Moderate Risk, 2.5 < LBGI < 5; and High Risk, LBGI > 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.
1 secondary outcome
Maximum Epinephrine Response (ADRR Groups)
Time frame: 285 min (time of clamp)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21175266Pitsillides AN, Anderson SM, Kovatchev B. Hypoglycemia risk and glucose variability indices derived from routine self-monitoring of blood glucose are related to laboratory measures of insulin sensitivity and epinephrine counterregulation. Diabetes Technol Ther. 2011 Jan;13(1):11-7. doi: 10.1089/dia.2010.0103.
- Derived from this study: PubMed 22167126Chan A, Barrett EJ, Anderson SM, Kovatchev BP, Breton MD. Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus. Diabetologia. 2012 Mar;55(3):729-36. doi: 10.1007/s00125-011-2402-3. Epub 2011 Dec 14.
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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.
Boris Kovatchev, Ph.D. principal investigator
University of Virginia Health Systems - Behavioral Medicine 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 Hyperinsulinemic, euglycemic and hypoglycemic clamp in people with Diabetes Mellitus, Type 1, run by University of Virginia 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 4 inclusion and 10 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 8 Sep 2014. 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 8 Sep 2014). 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?
Maximum Epinephrine Response (LBGI Groups) (time frame: 285 min (time of clamp)). 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 NCT00943787, which also lists 2 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 8 Sep 2014; AzTrials last refreshed its copy on 8 Nov 2026.