Type 2 DiabetesNCT01660009
Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans
A study testing Glycemic clamping in people with Type 2 Diabetes, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Glycemic clamping
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Jun 2017
- Phase
- Interventional
- 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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Type 2 Diabetes Inclusion Criteria
- Adult age 21 or older
- If on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reductase therapy, must be on a stable dose for at least 6 weeks prior to enrollment
- Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- Score of < 4 using the Gold method for assessing hypoglycemia awareness
- Adult age 21 or older
- No evidence of metabolic syndrome or diabetes, hypertension (BP≥140/90), or high cholesterol (LDL≥160) at the time of screen.
Who cannot join
- History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 40% on angiography or by confirmed history of myocardial infarction by standard criteria)
- Evidence of other evident major illness including chronic renal insufficiency(plasma creatinine > 1.4 for women or 1.5 for men), liver disease (aspartate aminotransferase or alanine aminotransferase greater than 2.5 x normal), and cancer currently undergoing therapy or had therapy for cancer within 1 year of enrollment.
- Pregnancy as determine by urinary pregnancy test
- Subjects on warfarin, oral anti-thrombin inhibitors, or thienopyridines
- Subjects who have had changes to dosing of thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, or metformin therapy within 6 weeks of enrollment.
- Failed Allen's test in both arms - unable to safely place an arterial line
Show all 17Show fewer
- Glucose reading of < 50 mg/dL and/or episodes of symptomatic hypoglycemia requiring the assistance of another person for recovery in the 2 years prior to enrollment.
- History of hypoglycemic convulsions
- Current fluoxetine therapy (known to interfere with neuroendocrine response to hypoglycemia)
- Glycosylated hemoglobin over 8.5%
- On aldosterone antagonist therapy at the time of enrollment
- On insulin therapy at the time of screening.
- History of allergy to local anesthetic injection like lidocaine.
- Age below 21.
- Meet any of the exclusion criteria for diabetic or metabolic syndrome group Meet criteria for type 2 diabetes or metabolic syndrome
- On medication for cholesterol or blood pressure.
- History of allergy to local anesthetic injection like lidocaine.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. In this study, we plan to study whether acute exposure of patients to clinically relevant (50-60 milligrams/deciliter) levels of hypoglycemia induces or worsens blood vessel endothelial dysfunction- a key 1st step in the development of heart attacks and strokes. This will be determined in humans both with and with type 2 diabetes.
- Conditions
- Type 2 Diabetes
- Being tested
- Glycemic clamping
- Keywords
- Endothelial Function, Hypoglycemia, Mitochondria
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glycemic clampingOther
During hypoglycemic clamping, individuals will have a blood glucose level of 50-60 mg/dL for approximately 1 hour prior to outcome measurements. During euglycemic clamping, individuals will have a blood glucose level of 85-99 mg/dL for approximately 1 hour prior to outcome measurements.
| Study group | Role | What they receive |
|---|---|---|
| Hypoglycemia First | Experimental | Individuals will undergo a hyperinsulinemic hypoglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit. Receives: Other: Glycemic clamping |
| Euglycemia First | Experimental | Individuals will undergo a hyperinsulinemic euglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit. Receives: Other: Glycemic clamping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow induced Dilation of the Brachial Artery (FMD%)
Measured: 1 hour
Secondary outcomes (3)
Measurement of total and phosphorylated endothelium-derived NO synthase expression in radial artery endothelial cells.
Measured: 1 hour
Measurement of mitochondrial membrane potential
Performed on captured radial artery endothelial cells.
Measured: 1 hour
Mitochondrial superoxide production
From capture radial artery endothelial cells.
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2017
- Study completionJun 2017
Why it stopped: Insufficient Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael E Widlansky, MD, MPH, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660009
- Sponsor's protocol ID
- MCW-MEW3
- Status last verified
- Apr 2015
- First submitted
- 6 Aug 2012
- Last updated
- 14 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans
- ClinicalTrials.gov ID
- NCT01660009
- Acronym / sponsor ID
- MCW-MEW3
- Conditions
- Type 2 Diabetes
- Keywords
- Endothelial Function, Hypoglycemia, Mitochondria
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient Funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 8 Aug 2012 (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.
Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. In this study, we plan to study whether acute exposure of patients to clinically relevant (50-60 milligrams/deciliter) levels of hypoglycemia induces or worsens blood vessel endothelial dysfunction- a key 1st step in the development of heart attacks and strokes. This will be determined in humans both with and with type 2 diabetes.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoglycemia First | Experimental | Other: Glycemic clampingIndividuals will undergo a hyperinsulinemic hypoglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit. |
| Euglycemia First | Experimental | Other: Glycemic clampingIndividuals will undergo a hyperinsulinemic euglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type 2 Diabetes Inclusion Criteria
- Adult age 21 or older
- If on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reductase therapy, must be on a stable dose for at least 6 weeks prior to enrollment
- Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- Score of < 4 using the Gold method for assessing hypoglycemia awareness
Key exclusion criteria (17 listed)
- History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 40% on angiography or by confirmed history of myocardial infarction by standard criteria)
- Evidence of other evident major illness including chronic renal insufficiency(plasma creatinine > 1.4 for women or 1.5 for men), liver disease (aspartate aminotransferase or alanine aminotransferase greater than 2.5 x normal), and cancer currently undergoing therapy or had therapy for cancer within 1 year of enrollment.
- Pregnancy as determine by urinary pregnancy test
- Subjects on warfarin, oral anti-thrombin inhibitors, or thienopyridines
- Subjects who have had changes to dosing of thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, or metformin therapy within 6 weeks of enrollment.
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 |
|---|---|---|
| Glycemic clampingDuring hypoglycemic clamping, individuals will have a blood glucose level of 50-60 mg/dL for approximately 1 hour prior to outcome measurements. During euglycemic clamping, individuals will have a blood glucose level of 85-99 mg/dL for approximately 1 hour prior to outcome measurements. | Other | Euglycemia First, Hypoglycemia First |
Primary outcome
Flow induced Dilation of the Brachial Artery (FMD%)
Time frame: 1 hour
3 secondary outcomes
Measurement of total and phosphorylated endothelium-derived NO synthase expression in radial artery endothelial cells.
Time frame: 1 hour
Measurement of mitochondrial membrane potential
Time frame: 1 hour
Mitochondrial superoxide production
Time frame: 1 hour
Results and safety
The study was stopped early (reason given: Insufficient Funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2017.
Related trials for Type 2 Diabetes
Not yet recruiting
SWitching to Appropriate Prescription in Cardiovascular-Kidney-Metabolic Syndrome
Cardiovascular-kidney-metabolic Syndrome, Diabete Type 2
Active, not recruiting
Pilot of Continuous Glucose Monitor-Augmented Food Is Medicine
Nutrition, Type 2 Diabetes
Recruiting
Whole Food for Families: A Pilot RCT of a Dietary Guidelines-Based Intervention to Prevent Type 2 Diabetes
PreDiabetes, Diet, Healthy
Not yet recruiting
Safety and Efficacy of the Fully Closed Loop iLet Bionic Pancreas in Adults With Type 1 and Type 2 Diabetes
Diabetes (Insulin-requiring, Type 1 or Type 2)
Recruiting
6-Weeks of Blood Flow Restriction Training on Immune Cell Function and Bioenergetics
Type 2 Diabetes
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.
Michael E Widlansky, MD, MPH principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glycemic clamping in people with Type 2 Diabetes, run by Medical College of Wisconsin 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 7 inclusion and 17 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: stopped early, as of the sponsor's last update on 14 Aug 2017. 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?
The study was stopped early (reason given: Insufficient Funding). Results are not available in the source record.
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?
Flow induced Dilation of the Brachial Artery (FMD%) (time frame: 1 hour). 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 14 Aug 2017.