Glucose Clamp Study for Low Blood Sugar

Overseen By Maka Siamashvili, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Hypertension, Heart disease, Tobacco, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1 day per intervention

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how varying levels of low blood sugar affect blood vessels and clotting in healthy individuals. Participants will undergo a glucose clamp procedure, which maintains a constant blood sugar level, with blood sugar controlled at one of four levels: 50, 60, 70, or 90 mg/dl for 90 minutes. The trial is designed for individuals with a body mass index over 21 who do not have health issues such as heart disease or high blood pressure. Understanding these effects could improve the management of conditions related to low blood sugar. As an Early Phase 1 trial, this research focuses on how these procedures impact the body, allowing participants to contribute to foundational scientific knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulant drugs.

What prior data suggests that the glucose clamp technique is safe for humans?

Research has shown that the glucose clamp method is often used to study the effects of low blood sugar. This method is safe and precise, controlling blood sugar by adjusting the amount of sugar administered in real-time. This allows for accurate measurements and management. Participants in previous studies have tolerated it well. Additionally, the glucose clamp is a standard tool in many studies, further supporting its safety. Please note that this trial is in an early phase, meaning the treatment is still under close study for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for low blood sugar, which often involve consuming sugary foods or drinks, the glucose clamp method precisely controls blood sugar levels by maintaining a steady glucose concentration for a set period. Researchers are excited about this technique because it allows for a highly controlled environment to study the body's response to different blood sugar levels. This could lead to a better understanding of how to manage hypoglycemia more effectively and develop more personalized treatment strategies for patients.

What evidence suggests that this glucose clamp method is effective for studying hypoglycemia?

Research has shown that glucose clamps effectively control blood sugar levels. This method maintains steady blood sugar, crucial for treating low blood sugar. In this trial, participants will undergo different glucose clamp interventions, keeping blood sugar at specific levels such as 50 mg/dl, 60 mg/dl, 70 mg/dl, or 90 mg/dl for 90 minutes. Studies have demonstrated that the glucose clamp technique reveals how the body reacts to varying blood sugar levels. By maintaining these specific levels, researchers can observe the body's response to low blood sugar. This method studies how blood vessels and other body systems react during low blood sugar in healthy individuals. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy individuals with a body mass index over 21 kg/m2. It's not suitable for smokers, those with significant heart issues, allergies to study meds, on blood thinners or anticoagulants, uncontrolled high blood pressure, recent fever or pneumonia, poor kidney/liver function, low/high WBC count, anemia or bleeding disorders.

Inclusion Criteria

Your body mass index is higher than 21.

Exclusion Criteria

You currently smoke or use tobacco products.

Pregnant women

Your total bilirubin level is higher than 2 mg/dl.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo glucose clamp interventions at varying levels (50, 60, 70, 90 mg/dl) for 90 minutes each to study the effects of hypoglycemia on vascular biology

1 day per intervention

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glucose clamp

Trial Overview The study tests how different levels of low blood sugar affect the body's vascular system in healthy people using a glucose clamp technique. The aim is to understand the biological impact of varying hypoglycemia intensities on vessels and clotting processes.

How Is the Trial Designed?

Group I: 90 mg/dl glucose clamp Experimental Treatment 1 Intervention

Glucose clamp intervention of 90 mg/dl maintained for 90 minutes.

Group II: 70 mg/dl glucose clamp Experimental Treatment 1 Intervention

Glucose clamp intervention of 70 mg/dl maintained for 90 minutes.

Group III: 60 mg/dl glucose clamp Experimental Treatment 1 Intervention

Glucose clamp intervention of 60 mg/dl maintained for 90 minutes.

Group IV: 50 mg/dl glucose clamp Experimental Treatment 1 Intervention

Glucose clamp intervention of 50 mg/dl maintained for 90 minutes.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

Published Research Related to This Trial

A new iterative computer program for glucose clamping provides a reliable and unbiased method for assessing insulin sensitivity and beta-cell function, applicable to both human and animal studies.

In a study of 151 clamp tests, the program achieved a median coefficient of variation of glucose values at the end of the clamp of just 2%, indicating high precision in maintaining target glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unbiased and flexible iterative computer program to achieve glucose clamping. Matthews, DR., Hosker, JP.[2019]

The RISE Consortium successfully standardized a hyperglycemic clamp protocol across seven centers, achieving high precision (3%-9% variance) and accuracy (SD < 10%) in glucose target levels, which is crucial for reliable diabetes research.

The methodology proved robust against variations in baseline physiology and treatment effects, ensuring consistent results across different populations, such as youth and adults with varying diabetes statuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision and accuracy of hyperglycemic clamps in a multicenter study. Mather, KJ., Tjaden, AH., Hoehn, A., et al.[2022]

The Biostator GCIIS effectively maintained stable blood glucose levels at hypoglycemic, euglycemic, and hyperglycemic states in normal subjects during a 2-hour insulin infusion study, demonstrating its utility in glucose clamp studies.

Despite some technical challenges, such as interruptions in blood flow and occasional discrepancies in glucose measurements, the system achieved low coefficients of variation in blood glucose levels, indicating reliable performance for glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose clamping using the Biostator GCIIS. Verdonk, CA., Rizza, RA., Westland, RE., et al.[2015]

The ClampArt device demonstrated high quality in glucose clamp procedures, achieving a trueness of 1.2 ± 2.5 mg/dl and a mean absolute relative difference (MARD) of 5.3 ± 2.3%, indicating its accuracy and reliability in measuring blood glucose levels.

With an operational time of 95.4% ± 4.1%, ClampArt shows excellent utility, making it a promising tool for future studies comparing automated and manual glucose clamp methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to Assess the Quality of Glucose Clamps? Evaluation of Clamps Performed With ClampArt, a Novel Automated Clamp Device. Benesch, C., Heise, T., Klein, O., et al.[2019]

A systematic review of 383 studies using the hyperinsulinaemic-hypoglycaemic clamp technique revealed significant variability in methodology, including insulin dosing (with a 49-fold difference), number of hypoglycaemic steps, and duration of the clamps, which could affect study outcomes.

Despite being the gold standard for studying hypoglycaemia, the lack of uniform standards in conducting these experiments means that results from different studies may not be directly comparable, highlighting the need for standardized protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperinsulinaemic-hypoglycaemic glucose clamps in human research: a systematic review of the literature. Fabricius, TW., Verhulst, CEM., Kristensen, PL., et al.[2023]

The study developed 17 virtual healthy subjects to simulate glucose clamp experiments, which can help train personnel in adjusting glucose infusion rates without needing real patients.

The virtual subjects accurately predicted plasma glucose and insulin levels during hyperglycemic clamp conditions, showing their potential for training and testing automated glucose clamp algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computer Simulation Model to Train Medical Personnel on Glucose Clamp Procedures. Maghoul, P., Boulet, B., Tardif, A., et al.[2018]

The automated clamp device ClampArt® significantly improves blood glucose measurement accuracy by correcting for blood dilution, reducing mean accuracy error from 8.1% to 4.1%.

This correction also enhances precision and control in glucose infusion rates, indicating that accounting for blood dilution is crucial for effective glucose management during clamps.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considering Blood Dilution improves the Precision of Continuous Whole Blood Glucose Measurements. Benesch, C., Kuhlenkötter, M., Heise, T.[2020]

A quality improvement project reviewed the efficacy of a Hypoglycemia Protocol for treating severe hypoglycemia in diabetic inpatients, finding that intravenous dextrose was significantly more effective than oral carbohydrates in achieving euglycemia (blood glucose ≥ 80 mg/dL) within 15 to 30 minutes post-treatment.

Out of 222 patients treated with oral carbohydrates, only 50 achieved euglycemia, compared to 106 out of 120 patients treated with intravenous dextrose, leading to a revision of the protocol to prioritize intravenous treatment for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Efficacy of a Hypoglycemia Protocol to Treat Severe Hypoglycemia. Gilmore, L., Freeman, S., Amarasekara, S., et al.[2022]

The improved algorithm implemented in the ClampArt device significantly reduced blood glucose (BG) and glucose infusion rate (GIR) oscillations, as demonstrated through in silico, in vitro, and in vivo experiments.

In a clinical study, the coefficient of variation for BG decreased from 6.0% to 4.2% and for GIR from 60.7% to 43.5%, indicating enhanced stability in glucose clamp quality without major changes to other parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Algorithm for Automated Glucose Clamps. Kuhlenkötter, M., Heise, T., Benesch, C.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7940281/

Hyperinsulinaemic–hypoglycaemic glucose clamps in ... The hyperinsulinaemic–hypoglycaemic glucose clamp technique has been developed and applied to assess effects of and responses to hypoglycaemia under ...

2. withpower.com withpower.com/trial/early-phase-1-hypoglycemia-6-2015-dbc77

Glucose Clamp Study for Low Blood Sugar This suggests that the glucose clamp can effectively manage blood sugar levels, which is crucial for treating low blood sugar. Show more ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2769657/

Hypoglycemia Detection and Prediction Using Continuous ... Results. Hypoglycemic clamp procedures start with elevated blood glucose, and glucose levels are brought close to 100 mg/dl before inducing hypoglycemia. ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01060917

Glucose Clamp Study to Prove Hypo- and Hyperglycemic ... The aim of this study is to evaluate the performance of a non-invasive glucose sensor (wristwatch) under controlled conditions (glucose clamp) at hyperglycemia ...

5. diabetesjournals.org diabetesjournals.org/care/article/45/3/520/139256/Beliefs-Around-Hypoglycemia-and-Their-Impacts-on

Beliefs Around Hypoglycemia and Their Impacts on ... With the growing use of CGMs (19) and emerging outcome data associated with their use, the recommended blood glucose levels for optimal daily ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6283439/

Continuous Glucose Monitoring for Hypoglycemia ... During the hypoglycemic clamp, plasma glucose by 60 minutes was near 80 mg/dL in all groups and overlapped thereafter during the 65-, 55-, and 45-mg/dL hourly ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04432090

GPR119 Agonist for Hypoglycemia in Type 1 Diabetes The purpose of this study is to test if a specific research medication could increase the response to low blood glucose in people with type 1 diabetes.

8. diabetesjournals.org diabetesjournals.org/care/article/36/10/2909/30303/Reduced-Hypoglycemia-and-Increased-Time-in-Target

Reduced Hypoglycemia and Increased Time in Target Using ... ... Hypoglycemia was defined as reference blood glucose <70 mg/dL. A treatable hypoglycemic event was defined as a reference blood glucose level <60 mg/dL.

9. prosciento.com prosciento.com/wp-content/uploads/library/ProSciento-Fact-Sheet-Hypoglycemic-Clamps.pdf

Hypoglycemic Clamp Studies Hypoglycemic clamps have been extensively used in studies of the pathophysiology of iatrogenic hypoglycemia. They are also used to study the effects of ...