Glucose Clamp Study for Low Blood Sugar

Recruiting in Baltimore (>99 mi)

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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the glucose clamp treatment for low blood sugar?

The glucose clamp method is shown to be precise and accurate in maintaining target blood sugar levels, as demonstrated by the RISE study, which achieved high precision and accuracy across multiple centers. This suggests that the glucose clamp can effectively manage blood sugar levels, which is crucial for treating low blood sugar. ^{1 2 3 4 5}

Is the glucose clamp procedure generally safe for humans?

The glucose clamp procedure is a well-established method used to study insulin and blood sugar levels, and it has been standardized across multiple study centers to ensure precision and accuracy. While the studies focus on the technical aspects of the procedure, the consistent use in research suggests it is generally considered safe when conducted by trained professionals. ^{1 2 5 6 7}

How is the glucose clamp treatment unique for low blood sugar?

The glucose clamp treatment is unique because it precisely controls blood sugar levels by adjusting glucose infusion rates in real-time, allowing for accurate assessment of insulin sensitivity and beta-cell function. This method is highly standardized and provides reliable results across different study centers, unlike other treatments that may not offer such precision. ^{1 4 7 8 9}

Eligibility Criteria

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

Pregnant women

You currently smoke or use tobacco products.

I have not been treated for pneumonia or hospitalized for it in the last 2 weeks.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Precision and accuracy of hyperglycemic clamps in a multicenter study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

How to Assess the Quality of Glucose Clamps? Evaluation of Clamps Performed With ClampArt, a Novel Automated Clamp Device. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the Efficacy of a Hypoglycemia Protocol to Treat Severe Hypoglycemia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Unbiased and flexible iterative computer program to achieve glucose clamping. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Considering Blood Dilution improves the Precision of Continuous Whole Blood Glucose Measurements. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Improved Algorithm for Automated Glucose Clamps. [2017]

7. Canada pubmed.ncbi.nlm.nih.gov

Computer Simulation Model to Train Medical Personnel on Glucose Clamp Procedures. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Hyperinsulinaemic-hypoglycaemic glucose clamps in human research: a systematic review of the literature. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Glucose clamping using the Biostator GCIIS. [2015]