HypoglycemiaEarly Phase 1NCT02445781
Differing Levels of Hypoglycemia
A Early Phase 1 study testing Glucose clamp in people with Hypoglycemia, run by University of Maryland, Baltimore at 2 sites in United States.
Trial summary
Hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. To date no studies appear to have investigated the effects of differing levels of hypoglycemia on the vasculature and pro-atherothrombotic balance during hypoglycemia in healthy man. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia
- What is being tested?
- Glucose clamp
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2015to Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Body mass index >21kg · m-2
Who cannot join
- Pregnant women
- Subjects unwilling or unable to comply with approved contraception measures
- Subjects unable to give voluntary informed consent
- Subjects on anticoagulant drugs, anemic or with known bleeding diatheses
- Subjects with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents
- Current tobacco use
Show all 24Show fewer
- Subjects with any known allergies to any of the study medications being used
- Physical Exam Exclusion Criteria
- Uncontrolled severe hypertension (i.e., blood pressure greater than 160/100)
- Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmia)
- Pneumonia treatment or hospitalization within 2 weeks prior to enrollment (study visit)
- Hepatic failure / jaundice
- Renal failure
- Cerebrovascular accident occurrence or hospitalization within 4 weeks prior to enrollment
- Fever greater than 38.0 degrees C
- Screening Laboratory Tests Exclusion Criteria
- Hematocrit lower than 32 %
- White blood cell (WBC) count lower than 3 thou/ul or greater than 14 thou/ul
- Liver function tests: serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) greater than twice upper limit of normal range
- Alkaline phosphatase greater than 150U/L
- Total bilirubin (TBil) greater than 2 mg/dl
- Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2
- Positive human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
- Any abnormal cardiac response during multi-stage exercise test (if over 40 years of age)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Maryland, Baltimore
Baltimore, Maryland, 21201
Maka Siamashvili, MD, 410-706-5623
Stephen N Davis, MBBS
- Recruiting
University of Maryland, Baltimore
Baltimore, Maryland, 21201
Maka Siamashvili, MD, 410-706-5623
Maka Hedrington, MD, 410-706-5623, msiamashvili@som.umaryland.edu
About this study
Official title: Mechanisms of Hypoglycemia Associated Autonomic Dysfunction, Differing Levels of Hypoglycemia
Hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. To date no studies appear to have investigated the effects of differing levels of hypoglycemia on the vasculature and pro-atherothrombotic balance during hypoglycemia in healthy man. The specific aim of our study will be to determine the effects of differing levels of hypoglycemia on in-vivo vascular biologic mechanisms in a healthy population.
Read the detailed description
Recent large randomized multicenter trials have investigated the effects of lowering blood glucose levels towards normal in both inpatient and ambulatory care/community settings. All studies have reported increasing prevalence and incidence of hypoglycemia as glucose levels approach normal. In fact, the occurrence of hypoglycemia was so problematic that some hospital based studies were halted and the target recommendations for glucose levels in critically unwell patients have been increased. Similarly three recent large glucose control and complications trials in type 2 diabetes mellitus (DM) have reported significantly high rates of hypoglycemia in intensively treated type 2 DM individuals. In two of these studies (VADT, ADVANCE) there was a highly significant association between severe hypoglycemia (glucose low enough to cause neurologic impairment) and serious cardiac events and increased death. Furthermore, in two studies performed in the USA (VADT, ACCORD), severe hypoglycemia occurring in the standard/conventionally treated group produced even more serious adverse cardiac effects as compared to the intensively treated group. The in-vivo mechanism(s) responsible for the above findings could not be identified from the above studies. Surprisingly there is very limited data available regarding the effects of hypoglycemia on in-vivo vascular biology. Previously, in vitro work has determined that epinephrine, norepinephrine, growth hormone, glucagon, and corticosteroids (all counterregulatory hormones) can have vascular biologic effects (platelet aggregation, fibrinolytic balance, increases in pro-inflammatory markers and changes in endothelial function). Three recent studies from my own and other laboratories performed in healthy volunteers and type 1 DM have demonstrated that hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. Novel preliminary data from my lab has also demonstrated that hypoglycemia can impair endothelial function, reduce fibrinolytic balance (increase plasminogen activator inhibitor-1) and produce pro-atherothrombotic (increase platelet aggregation, thrombin anti-thrombin complexes, vascular adhesion molecules) changes in type 2 DM. Additionally, preliminary data presented below will demonstrate that a 90 minute episode of hypoglycemia (50 mg/dl) produces similar pro-atherothrombotic changes as compared to 4 hours of hyperglycemia (200 mg/dl). However, as investigators are just beginning to realize the effects of hypoglycemia on vascular biology, there remain many unanswered questions. For example, in the vulnerable type 2 DM population what is the dose response of different levels of hypoglycemia with attendant ANS activation on endothelial function and atherothrombotic balance? How does level of glycemic control affect ANS and vascular biologic responses to hypoglycemia in type 2 DM? Proposed studies in this protocol will provide novel information answering the clinically important question regarding the effects of mild to moderate hypoglycemia on vascular biologic mechanisms in a healthy population.
- Conditions
- Hypoglycemia
- Being tested
- Glucose clamp
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucose clampDevice
Different levels of hypoglycemia
| Study group | Role | What they receive |
|---|---|---|
| 90 mg/dl glucose clamp | Experimental | Glucose clamp intervention of 90 mg/dl maintained for 90 minutes. Receives: Device: Glucose clamp |
| 70 mg/dl glucose clamp | Experimental | Glucose clamp intervention of 70 mg/dl maintained for 90 minutes. Receives: Device: Glucose clamp |
| 60 mg/dl glucose clamp | Experimental | Glucose clamp intervention of 60 mg/dl maintained for 90 minutes. Receives: Device: Glucose clamp |
| 50 mg/dl glucose clamp | Experimental | Glucose clamp intervention of 50 mg/dl maintained for 90 minutes. Receives: Device: Glucose clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow mediated vasodilation of brachial artery measurements (mean maximum % change)
baseline (pre) measurements compared to end of clamp (post) measurements
Measured: 120 minutes (pre) clamp and 240 minutes (post) clamp
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study startJul 2015
- Primary completionSep 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoglycemiaStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University
- Responsible party
- Principal investigator, Stephen N. Davis, MBBS, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445781
- Sponsor's protocol ID
- 00064405
- Status last verified
- Nov 2025
- First submitted
- 8 May 2015
- Last updated
- 10 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Hypoglycemia Associated Autonomic Dysfunction, Differing Levels of Hypoglycemia
- ClinicalTrials.gov ID
- NCT02445781
- Acronym / sponsor ID
- 00064405
- Conditions
- Hypoglycemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Vanderbilt University
- Study start
- Jul 2015
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 15 May 2015 (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.
Hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. To date no studies appear to have investigated the effects of differing levels of hypoglycemia on the vasculature and pro-atherothrombotic balance during hypoglycemia in healthy man. The specific aim of our study will be to determine the effects of differing levels of hypoglycemia on in-vivo vascular biologic mechanisms in a healthy population.
Detailed description
Recent large randomized multicenter trials have investigated the effects of lowering blood glucose levels towards normal in both inpatient and ambulatory care/community settings. All studies have reported increasing prevalence and incidence of hypoglycemia as glucose levels approach normal. In fact, the occurrence of hypoglycemia was so problematic that some hospital based studies were halted and the target recommendations for glucose levels in critically unwell patients have been increased. Similarly three recent large glucose control and complications trials in type 2 diabetes mellitus (DM) have reported significantly high rates of hypoglycemia in intensively treated type 2 DM individuals. In two of these studies (VADT, ADVANCE) there was a highly significant association between severe hypoglycemia (glucose low enough to cause neurologic impairment) and serious cardiac events and increased death. Furthermore, in two studies performed in the USA (VADT, ACCORD), severe hypoglycemia occurring in the standard/conventionally treated group produced even more serious adverse cardiac effects as compared to the intensively treated group. The in-vivo mechanism(s) responsible for the above findings could not be identified from the above studies. Surprisingly there is very limited data available regarding the effects of hypoglycemia on in-vivo vascular biology. Previously, in vitro work has determined that epinephrine, norepinephrine, growth hormone, glucagon, and corticosteroids (all counterregulatory hormones) can have vascular biologic effects (platelet aggregation, fibrinolytic balance, increases in pro-inflammatory markers and changes in endothelial function). Three recent studies from my own and other laboratories performed in healthy volunteers and type 1 DM have demonstrated that hypoglycemia can produce a spectrum of pro-inflammatory and pro-atherothrombotic changes. Novel preliminary data from my lab has also demonstrated that hypoglycemia can impair endothelial function, reduce fibrinolytic balance (increase plasminogen activator inhibitor-1) and produce pro-atherothrombotic (increase platelet aggregation, thrombin anti-thrombin complexes, vascular adhesion molecules) changes in type 2 DM. Additionally, preliminary data presented below will demonstrate that a 90 minute episode of hypoglycemia (50 mg/dl) produces similar pro-atherothrombotic changes as compared to 4 hours of hyperglycemia (200 mg/dl). However, as investigators are just beginning to realize the effects of hypoglycemia on vascular biology, there remain many unanswered questions. For example, in the vulnerable type 2 DM population what is the dose response of different levels of hypoglycemia with attendant ANS activation on endothelial function and atherothrombotic balance? How does level of glycemic control affect ANS and vascular biologic responses to hypoglycemia in type 2 DM? Proposed studies in this protocol will provide novel information answering the clinically important question regarding the effects of mild to moderate hypoglycemia on vascular biologic mechanisms in a healthy population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 90 mg/dl glucose clamp | Experimental | Device: Glucose clampGlucose clamp intervention of 90 mg/dl maintained for 90 minutes. |
| 70 mg/dl glucose clamp | Experimental | Device: Glucose clampGlucose clamp intervention of 70 mg/dl maintained for 90 minutes. |
| 60 mg/dl glucose clamp | Experimental | Device: Glucose clampGlucose clamp intervention of 60 mg/dl maintained for 90 minutes. |
| 50 mg/dl glucose clamp | Experimental | Device: Glucose clampGlucose clamp intervention of 50 mg/dl maintained for 90 minutes. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Body mass index >21kg · m-2
Key exclusion criteria (24 listed)
- Pregnant women
- Subjects unwilling or unable to comply with approved contraception measures
- Subjects unable to give voluntary informed consent
- Subjects on anticoagulant drugs, anemic or with known bleeding diatheses
- Subjects with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents
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 clampDifferent levels of hypoglycemia | Device | 50 mg/dl glucose clamp, 60 mg/dl glucose clamp, 70 mg/dl glucose clamp, 90 mg/dl glucose clamp |
Primary outcome
Flow mediated vasodilation of brachial artery measurements (mean maximum % change)
Time frame: 120 minutes (pre) clamp and 240 minutes (post) clamp
baseline (pre) measurements compared to end of clamp (post) measurements
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Glucose clamp in people with Hypoglycemia, run by University of Maryland, Baltimore at 2 sites 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 1 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maka Siamashvili, MD (410-706-5623, msiamashvili@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow mediated vasodilation of brachial artery measurements (mean maximum % change) (time frame: 120 minutes (pre) clamp and 240 minutes (post) clamp). 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 10 Nov 2025.