Glucose and Amino Acids for High Blood Sugar

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must be taking: Sulfonylureas, Metformin

Must not be taking: Insulin, Glucose-lowering agents

Disqualifiers: Pregnancy, Abdominal surgery, Systemic illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 240 minutes

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to better understand how amino acids alter the release of glucagon and insulin compared to glucose alone in health and disease.

Will I have to stop taking my current medications?

If you have type 2 diabetes, you can continue taking sulfonylureas or metformin. However, if you are obese without diabetes or lean without diabetes, you cannot use any glucose-lowering medications, including metformin or sulfonylureas.

How does the drug Clinisol 15% with Dextrose differ from other treatments for high blood sugar?

Clinisol 15% with Dextrose is unique because it combines glucose with amino acids, which may help tissues use amino acids more effectively and manage blood sugar levels. This combination can lead to a reduced glucose response and a modest increase in insulin, offering a different approach compared to standard glucose-lowering treatments. ^{1 2 3 4 5}

Research Team

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for people with high blood sugar, obesity, or type 2 diabetes. Diabetic participants need an HbA1c level below 8.5%, while obese and lean individuals must have it under 6.5%. Obese subjects should have a BMI of at least 28, and lean ones a BMI up to 25. Only diabetics on sulfonylureas or metformin can join, and women must not be pregnant. Those with major surgeries, active illnesses like cancer, severe vascular diseases, or who can't undergo MRI are excluded.

Inclusion Criteria

No contraindications to MRI (e.g., metal implants, claustrophobia).

I only use sulfonylureas or metformin for my type 2 diabetes.

HbA1c ≤ 6.5% (obese and lean subjects).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an IV infusion of glucose and either saline or amino acids, with frequent blood draws to monitor blood glucose levels

240 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Clinisol 15%
• Dextrose

Trial Overview The study tests how amino acids (using Clinisol) affect glucagon and insulin release compared to glucose alone (using Dextrose). It aims to understand these effects in healthy individuals as well as those with obesity or type 2 diabetes.

Participant Groups

Group I: Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Saline and Glucose Experimental Treatment 1 Intervention

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of saline and glucose (50%) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Group II: Healthy Adults, Obese Adults, Adults with Type 2 diabetes: Amino Acid and Glucose Experimental Treatment 2 Interventions

Study visit: Subjects will receive a caffeine free, standardized evening meal and remain fasting overnight. An IV infusion of glucose (50%) will be given the next morning together with an IV infusion of Clinisol 15% (an amino acid mixture) will be given the next morning and continue until the end of study. Blood draws will be collected frequently from the IV line to monitor blood glucose levels.

Clinisol 15% is already approved in United States for the following indications:

Approved in United States as Clinisol SF for:

• Nutrition support for patients requiring parenteral nutrition (PN) when oral or enteral intake is not possible, insufficient, or contraindicated
• Treatment of negative nitrogen balance in patients where the alimentary tract cannot or should not be used, gastrointestinal absorption of protein is impaired, or metabolic requirements for protein are substantially increased, as with extensive burns

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study of premature infants weighing under 1500 g, alternating intravenous administration of hypertonic glucose and Aminosol-glucose led to increased plasma insulin and growth hormone levels, but did not improve nitrogen utilization from amino acids, with over 50% of administered nitrogen being excreted.

The hormonal responses to the glucose and amino acid infusions did not prevent metabolic acidosis, which was variable but generally compensated, indicating that while the treatment altered hormone levels, it did not effectively enhance the metabolic benefits expected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic and hormonal effects of alternate infusion of hypertonic glucose and aminosol-glucose in premature infants. Rubecz, I., Mestyán, J., Soltész, G., et al.[2013]

Ingesting leucine and glycine together with glucose significantly reduced the glucose response by 66% and increased insulin levels by 24% compared to glucose alone, indicating a beneficial effect on blood sugar control.

However, the combined effect of leucine and glycine on glucose response was not additive compared to their individual effects, suggesting a complex interaction that requires further investigation to understand the underlying mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction of ingested leucine with glycine on insulin and glucose concentrations. Iverson, JF., Gannon, MC., Nuttall, FQ.[2021]

Enamine derivatives, particularly sodium DL-phenylalanate, significantly enhance the rectal absorption of insulin in normal rabbits, suggesting a potential method for improving insulin delivery.

In diabetic rabbits, insulin formulations containing these enamines effectively lowered serum glucose levels to normal for over 2.5 hours, with gelatin microenemas showing superior insulin absorption compared to traditional suppositories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits. Kim, S., Kamada, A., Higuchi, T., et al.[2019]

The experimental solution P900, when combined with 5 mg of cortisol/liter, can be safely infused through peripheral veins for extended periods (average 114 hours) and improves nutritional balances in undernourished subjects, preventing negative balances of nitrogen, phosphorus, magnesium, and potassium.

P900 with cortisol, along with a daily oral intake of 670-1700 calories, provides nutritional benefits comparable to the concentrated hyperalimentation solution C1,800, indicating its potential as an effective alternative for nutritional support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral nutrition of adults with a 900 milliosmolar solution via peripheral veins. Isaacs, JW., Millikan, WJ., Stackhouse, J., et al.[2018]

In a study of 68 neonates requiring parenteral nutrition, those treated with Vamin 9 glucose had a higher mortality rate, especially in infants weighing 1000 grams or more, compared to those receiving MB233G.

The MB233G preparation was found to maintain plasma amino acid levels within the normal range for newborns, while Vamin 9 glucose led to significantly elevated levels of certain amino acids, indicating potential safety concerns with Vamin 9 glucose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial of two parenteral nutrition solutions in neonates. McIntosh, N., Mitchell, V.[2019]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

Metabolic and hormonal effects of alternate infusion of hypertonic glucose and aminosol-glucose in premature infants. [2013]

2. Egypt pubmed.ncbi.nlm.nih.gov

Interaction of ingested leucine with glycine on insulin and glucose concentrations. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits. [2019]

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

Parenteral nutrition of adults with a 900 milliosmolar solution via peripheral veins. [2018]

5. England pubmed.ncbi.nlm.nih.gov

A clinical trial of two parenteral nutrition solutions in neonates. [2019]