Diabetes Mellitus, Type 1NCT01835964
Biobehavioral Mechanisms of Glucose Variability
A study testing Glucose Variability Observation in people with Diabetes Mellitus, Type 1, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to investigate how blood sugar changes in response to insulin and what the body does to counter-act low blood sugar in people with Type 1 Diabetes Mellitus. Insulin sensitivity is the term used to describe blood sugar changes within the body in response to insulin. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Glucose Variability Observation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Feb 2014
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of type 1 diabetes mellitus for ≥2 years. For an individual to be enrolled at least one criterion from each list must be met.
- Criteria for documented hyperglycemia (at least 1 must be met):
- Fasting Blood Glucose (BG) ≥126 mg/dL
- 2h Oral Glucose Tolerance Test (OGTT) ≥200 mg/dL
- Hemoglobin (HbA1c) ≥6.5%
- BG ≥200 mg/dL with symptoms
Show all 20Show fewer
- History of hyperglycemia consistent with diabetes
- Criteria for requiring insulin at diagnosis (1 must be met):
- required insulin at diagnosis and continually thereafter
- no insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and insulin eventually required and used continually
- no insulin at diagnosis but continued hyperglycemia, positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and insulin eventually required and used continually
- Use of an insulin pump for at least six months prior to the study.
- Using a bolus calculator with pre-defined parameters for carbohydrate ratio(s), and insulin sensitivity factor(s).
- Signed informed consent.
- Age ≥21 and <65 years old.
- HbA1c ≤10% as measured with DCA 2000 or equivalent device.
- Willingness to use lispro (Humalog) insulin for metabolic challenge admission.
- Willingness to perform self-monitoring blood glucose (SMBG) >4 times/day.
- Willingness to avoid consumption of acetaminophen-containing products during the study.
- Willingness to perform 4 days of outpatient assessment with timed, prepackaged meals and snacks, and >7 SMBGs.
Who cannot join
- Uncontrolled arterial hypertension (resting blood pressure >160/100 mm Hg).
- Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥3 times the upper reference limit.
- Impaired renal function: glomerular filtration rate (calc GFR) of <60 ml/min/1.73 m2.
- Diabetic ketoacidosis in the past 6 months
- Conditions which may increase the risk of induced hypoglycemia such as:
- uncontrolled coronary artery disease
Show all 40Show fewer
- stable or unstable angina
- episode of chest pain of cardiac etiology with documented Electrocardiography changes or positive troponin levels
- positive stress test
- catheterization with coronary blockages >50%
- congestive heart failure
- significant cardiac arrhythmia
- history of a cerebrovascular event
- seizure disorder
- syncope
- adrenal insufficiency
- hypoglycemia-induced migraine within the past year
- neurological disease
- Diabetic complications altering insulin kinetics or food absorption
- Pregnancy, breast-feeding or intention of becoming pregnant.
- Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
- Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment).
- skin condition that prevents sensor placement on the abdomen or arm.
- Difficulties to operate Continuous Glucose Monitor.
- Uncontrolled thyroid disease: thyroid-stimulating hormone (TSH)>10.
- Bleeding diathesis or dyscrasia.
- Alcohol or drug abuse within 1 year of enrollment by patient history.
- Allergy to components of the CGM sensor.
- Blood donation >473 ml in last 56 days
- Prior noncompliance with study procedures.
- Hematocrit outside of the normal range.
- Magnesium <1.6 mg/dl.
- Potassium <3.4 mmol/L.
- Active enrollment in another clinical trial
- Allergy to or intolerance of insulin lispro (Humalog)
- Anticoagulant therapy other than aspirin.
- Oral steroids.
- Use of acetaminophen-containing medication that cannot be.
- Use of Type 2 Diabetes Mellitus medications: including metformin, sulfonylureas, meglitinides, thiazolidinediones, Dipeptidyl peptidase-4 (DPP-IV) inhibitors, glucagonlike Peptide (GLP-1) agonists and alpha-glucosidase inhibitors.
- Unwillingness to withhold Pramlintide for the duration of the study intervention.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22904
About this study
The purpose of this study is to investigate how blood sugar changes in response to insulin and what the body does to counter-act low blood sugar in people with Type 1 Diabetes Mellitus. Insulin sensitivity is the term used to describe blood sugar changes within the body in response to insulin. Greater understanding of insulin sensitivity, particularly how the body responds to low blood sugar, will help us to better predict how blood sugar levels will change.
All subjects will receive a liquid mixed-meal and will have their blood sugar response monitored in order to study insulin sensitivity. All subjects will receive additional insulin injections that are given to cause a low blood sugar in order to understand how the body responds to a low blood sugar. All subjects will be closely monitored during the time the insulin is given, by frequent checks of blood sugar and constant medical and nursing supervision. Details of the visits, tests and procedures are described below. During this study, the study team will ask that subjects to use their own insulin pump and own glucometer. Subjects will need to use the same glucometer for the entire study. Subjects will be provided 1 box of strips. Subjects will be required to use lispro (Humalog) insulin 2-3 days before your inpatient admission which will be provided free of charge.
Read the detailed description
Glucose variability (GV) in type 1 diabetes (T1DM) is increasingly viewed as a primary marker of glycemic control, responsible, along with chronic hyperglycemia reflected by HbA1c, for diabetes complications. In this study, we propose to investigate: (i) the time course of deterioration of physiological glucoregulatory mechanisms leading to increased GV, and (ii) the association of GV with metabolic and behavioral factors such as insulin sensitivity and treatment adequacy. Our primary hypothesis is:
Glucose variability in T1DM is triggered by behavioral events (e.g. meals, insulin injection, exercise) that challenge the metabolic system. The timing and the magnitude of the behavioral challenges, and the ability of the metabolic mechanisms to absorb these challenges, determine the magnitude of GV. This process develops in a certain time frame, and can be accelerated by inadequate treatment, or attenuated by precise timing and dosing of bio-behavioral control. This study will use a combination of treatment records, continuous glucose monitoring (CGM), and an inpatient admission to clarify the relationships between behavioral challenges to the metabolic system, physiological glucoregulatory mechanisms, and GV. This study will test the following hypotheses:
- Suboptimal treatment behavior, e.g. insulin mistiming (early/late meal insulin) or unbalanced insulin (higher basal/bolus ratio), is correlated with higher GV and repeated hypo- and hyperglycemia; this relationship is mediated by a patients' insulin sensitivity;
- A metabolic challenge (e.g. consecutive sequence of hypo- and hyperglycemia), will push the metabolic system into a transient super-critical state characterized by increased GV as defined by the Variability Grid Analysis (VGA) and the Average Daily Risk Range (ADRR), which will persist for several days beyond the discontinuation of the challenge.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Glucose Variability Observation
- Keywords
- Glucose Variability (GV), Continuous Glucose Monitor (CGM), Average Daily Risk Range (ADRR), Self Monitoring Blood Glucose (SMBG)
- 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.
Glucose Variability ObservationProcedure or surgery
On the morning of ~Day 17 for a metabolic challenge involving a standardized liquid mixed meal intended to raise the blood glucose approximately 150 mg/dl, followed four hours later by the induction of hypoglycemia with intravenous insulin administration with goal glucose of 55 mg/dl. After carbohydrate rescue, the subject will receive a meal and will be monitored until glucose is stable above 80 mg/dl.
| Study group | Role | What they receive |
|---|---|---|
| Glucose Variability Observation | Experimental | The study procedures will start after CGM device training \& practice using the blinded CGM for 2 days and will continue over the course of ~33 days. The study team will collect data about diabetes management including blood glucose data from fingerstick and CGM values along with insulin pump records throughout the 4 week observation period. Insulin sensitivity will be evaluated at home with predetermined meals' carbohydrate count. At the mid-study point glucose variability will be simulated in clinic with a metabolic challenge (liquid mixed meal) followed 4 hours later by the induction of hypoglycemia with an intravenous insulin injection. Insulin sensitivity, as well as glucagon and epinephrine counterregulatory responses will be evaluated to be related to overall Glucose Variability. Receives: Procedure: Glucose Variability Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change Between Pre and Post Challenge Glucose Variability
Glucose variability in the days leading to and following the challenge was assessed by computing Low Blood Glucose Index (LBGI) on daily self-monitoring of BG (SMBG) readings. Low LBGI values correspond to lower glucose variability associated with hypoglycemic risk. LBGI values lie between 0 and 100
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionJan 2014
- Study completionFeb 2014
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.
- 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
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- DexCom, Inc.
- Responsible party
- Principal investigator, Marc Breton, University of Virginia
- Investigators
- Marc Breton, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01835964
- Sponsor's protocol ID
- 16723
- Status last verified
- Aug 2022
- First submitted
- 11 Apr 2013
- Last updated
- 7 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biobehavioral Mechanisms of Glucose Variability
- ClinicalTrials.gov ID
- NCT01835964
- Acronym / sponsor ID
- 16723
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Glucose Variability (GV), Continuous Glucose Monitor (CGM), Average Daily Risk Range (ADRR), Self Monitoring Blood Glucose (SMBG)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- DexCom, Inc.
- Study start
- Apr 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 19 Apr 2013 (estimated)
- Results
- Posted 7 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate how blood sugar changes in response to insulin and what the body does to counter-act low blood sugar in people with Type 1 Diabetes Mellitus. Insulin sensitivity is the term used to describe blood sugar changes within the body in response to insulin. Greater understanding of insulin sensitivity, particularly how the body responds to low blood sugar, will help us to better predict how blood sugar levels will change.
All subjects will receive a liquid mixed-meal and will have their blood sugar response monitored in order to study insulin sensitivity. All subjects will receive additional insulin injections that are given to cause a low blood sugar in order to understand how the body responds to a low blood sugar. All subjects will be closely monitored during the time the insulin is given, by frequent checks of blood sugar and constant medical and nursing supervision. Details of the visits, tests and procedures are described below. During this study, the study team will ask that subjects to use their own insulin pump and own glucometer. Subjects will need to use the same glucometer for the entire study. Subjects will be provided 1 box of strips. Subjects will be required to use lispro (Humalog) insulin 2-3 days before your inpatient admission which will be provided free of charge.
Detailed description
Glucose variability (GV) in type 1 diabetes (T1DM) is increasingly viewed as a primary marker of glycemic control, responsible, along with chronic hyperglycemia reflected by HbA1c, for diabetes complications. In this study, we propose to investigate: (i) the time course of deterioration of physiological glucoregulatory mechanisms leading to increased GV, and (ii) the association of GV with metabolic and behavioral factors such as insulin sensitivity and treatment adequacy. Our primary hypothesis is:
Glucose variability in T1DM is triggered by behavioral events (e.g. meals, insulin injection, exercise) that challenge the metabolic system. The timing and the magnitude of the behavioral challenges, and the ability of the metabolic mechanisms to absorb these challenges, determine the magnitude of GV. This process develops in a certain time frame, and can be accelerated by inadequate treatment, or attenuated by precise timing and dosing of bio-behavioral control. This study will use a combination of treatment records, continuous glucose monitoring (CGM), and an inpatient admission to clarify the relationships between behavioral challenges to the metabolic system, physiological glucoregulatory mechanisms, and GV. This study will test the following hypotheses:
- Suboptimal treatment behavior, e.g. insulin mistiming (early/late meal insulin) or unbalanced insulin (higher basal/bolus ratio), is correlated with higher GV and repeated hypo- and hyperglycemia; this relationship is mediated by a patients' insulin sensitivity;
- A metabolic challenge (e.g. consecutive sequence of hypo- and hyperglycemia), will push the metabolic system into a transient super-critical state characterized by increased GV as defined by the Variability Grid Analysis (VGA) and the Average Daily Risk Range (ADRR), which will persist for several days beyond the discontinuation of the challenge.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glucose Variability Observation | Experimental | Procedure: Glucose Variability ObservationThe study procedures will start after CGM device training \& practice using the blinded CGM for 2 days and will continue over the course of ~33 days. The study team will collect data about diabetes management including blood glucose data from fingerstick and CGM values along with insulin pump records throughout the 4 week observation period. Insulin sensitivity will be evaluated at home with predetermined meals' carbohydrate count. At the mid-study point glucose variability will be simulated in clinic with a metabolic challenge (liquid mixed meal) followed 4 hours later by the induction of hypoglycemia with an intravenous insulin injection. Insulin sensitivity, as well as glucagon and epinephrine counterregulatory responses will be evaluated to be related to overall Glucose Variability. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Clinical diagnosis of type 1 diabetes mellitus for ≥2 years. For an individual to be enrolled at least one criterion from each list must be met.
- Use of an insulin pump for at least six months prior to the study.
- Using a bolus calculator with pre-defined parameters for carbohydrate ratio(s), and insulin sensitivity factor(s).
- Signed informed consent.
- Age ≥21 and <65 years old.
Key exclusion criteria (40 listed)
- Uncontrolled arterial hypertension (resting blood pressure >160/100 mm Hg).
- Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥3 times the upper reference limit.
- Impaired renal function: glomerular filtration rate (calc GFR) of <60 ml/min/1.73 m2.
- Diabetic ketoacidosis in the past 6 months
- Conditions which may increase the risk of induced hypoglycemia such as:
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 |
|---|---|---|
| Glucose Variability ObservationOn the morning of ~Day 17 for a metabolic challenge involving a standardized liquid mixed meal intended to raise the blood glucose approximately 150 mg/dl, followed four hours later by the induction of hypoglycemia with intravenous insulin administration with goal glucose of 55 mg/dl. After carbohydrate rescue, the subject will receive a meal and will be monitored until glucose is stable above 80 mg/dl. | Procedure or surgery | Glucose Variability Observation |
Primary outcome
Change Between Pre and Post Challenge Glucose Variability
Time frame: 3 days
Glucose variability in the days leading to and following the challenge was assessed by computing Low Blood Glucose Index (LBGI) on daily self-monitoring of BG (SMBG) readings. Low LBGI values correspond to lower glucose variability associated with hypoglycemic risk. LBGI values lie between 0 and 100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Marc Breton, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucose Variability Observation 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 20 inclusion and 40 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 7 Jul 2023. 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 7 Jul 2023). 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?
Change Between Pre and Post Challenge Glucose Variability (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2023.