Glucose and Fat Impact on Vascular Health

(REGAL Trial)

Overseen By Seth W Holwerda, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Kansas Medical Center

Must not be taking: Vitamin C, Vitamin E, Omega-3

Disqualifiers: Diabetes, Smoking, Hyperlipidemia, Hypertension, Heart disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 visits

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how sugar and fat in the blood affect blood vessels and whether this could lead to high blood pressure. Participants will receive infusions of either glucose (Dextrose 20% in 500 ML Injection) or lipids (fats), along with either vitamin C (ascorbic acid) or a placebo. The researchers seek to understand how these substances might alter blood vessel health. Ideal participants are lean, healthy adults with stable weight and normal blood pressure who do not take vitamin C, vitamin E, or omega-3 supplements. As an Early Phase 1 trial, this research focuses on understanding the effects of these substances on blood vessel health, offering participants the chance to contribute to groundbreaking insights.

Do I have to stop taking my current medications for the trial?

You will need to stop taking any vitamin C or E supplements or omega-3 fatty acids starting 2 weeks before the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dextrose infusions, like the one used in this study, are generally safe but require careful monitoring. Administering them too quickly or in large amounts can lead to high blood sugar and related issues.

Intralipid, a type of fat infusion, raises some concerns. Studies have found it can sometimes affect blood vessel linings. In rare cases, it has caused serious reactions, especially in newborns, though these are uncommon in healthy adults.

Both treatments have been used in other situations, indicating some level of safety, but they do carry risks. Prospective participants should be aware of these possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how glucose and lipid infusions, combined with ascorbic acid or placebo, impact vascular health differently from typical treatments. Unlike standard approaches that might focus on long-term medication or lifestyle changes, these infusions target the immediate effects of hyperglycemia and hyperlipidemia on blood vessels. The infusion method allows for precise control over glucose and lipid levels, which could lead to a better understanding of acute metabolic effects on vascular function. This trial could uncover new insights into managing vascular health, potentially leading to faster and more targeted interventions.

What evidence suggests that this trial's treatments could be effective for vascular health?

Research has shown that glucose, administered to participants in the "Glucose Infusion" arm of this trial, can impair blood vessel function, meaning the vessels might not work as effectively. High blood sugar levels can affect how well arteries perform their role. Similarly, studies indicate that Intralipid infusions, given to participants in the "Lipid Infusion" arm, can also damage blood vessel function, leading to higher blood pressure and stiffer vessels. Both treatments appear to impact blood vessel health, potentially helping researchers understand their role in high blood pressure. ^{2 3 6 7 8}

Who Is on the Research Team?

Seth W. W Holwerda, PhD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for lean, healthy adults aged 18-79 with normal insulin sensitivity and blood pressure below 140/90 mmHg. Participants should not have diabetes, a recent history of smoking, hyperlipidemia, hypertension or any cardiovascular diseases. They must be willing to stop taking vitamin C/E supplements and omega-3s two weeks prior.

Inclusion Criteria

You are not considered "lean," with a BMI (body mass index) below 25 kg/m

Your body processes insulin and sugar normally, as determined by specific blood tests.

Your blood pressure should be lower than 140 over 90.

Exclusion Criteria

You are currently smoking or have smoked in the past 3 months.

Your blood triglyceride levels should be less than 250 mg/dL after fasting.

Your blood pressure is higher than 130/80 mmHg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive I.V. glucose or lipid infusion with ascorbic acid or placebo

2 visits

2 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

• Ascorbic acid
• Dextrose 20 % in 500 ML Injection
• Intralipid
• Saline

Trial Overview The study investigates how glucose and fats affect blood vessels in the context of high blood pressure development. It involves administering Intralipid (a fat emulsion), Ascorbic acid (Vitamin C), Dextrose solution, and Saline to understand their impact on vascular function.

How Is the Trial Designed?

Group I: Lipid Infusion Experimental Treatment 3 Interventions

Hyperlipidemia (lipid infusion) will receive an I.V. Lipid infusion with a co-infusion of ascorbic acid or placebo at your visit 2 and the alternative treatment of ascorbic acid or placebo will be given on the subsequent study visit 3.

Group II: Glucose Infusion Experimental Treatment 3 Interventions

Hyperglycemia (glucose infusion) will receive an I.V. Glucose infusion with a co-infusion of ascorbic acid or placebo at your visit 2 and the alternative treatment of ascorbic acid or placebo will be given on the subsequent study visit 3.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1043067922002623

Cardioprotective Effects of Glucose-Insulin-Potassium ... The infusion of glucose-insulin-potassium lowers the risk of myocardial infarction while enhancing hemodynamics in patients undergoing on-pump cardiac surgery.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3738183/

Vascular effects of intravenous intralipid and dextrose ... In summary, our studies demonstrate that combined Intralipid and dextrose infusion impairs endothelial function. The co-administration of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04832009

Reversing Glucose and Lipid-mediated Vascular Dysfunction The purpose of our study is to understand the extent to which the blood vessels are affected by glucose and fat (lipids) in lean healthy adults and if these ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8582001/

Acute hyperglycaemia enhances both vascular endothelial ... Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans.

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.024648

Chelation Therapy in Patients With Cardiovascular Disease A meta‐analysis conducted with 4 studies reporting ankle‐brachial index indicated an improvement of 0.08 (95% CI, 0.06–0.09) from baseline.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/017521s069lbl.pdf

DEXTROSE injection, for intravenous use - accessdata.fda.gov 10 OVERDOSAGE​​ An increased infusion rate of Dextrose Injection or administration of a concentrated dextrose solution can cause hyperglycemia, hyperosmolality, ...

7. icumed.com icumed.com/media/ktql3hqr/en-4695.pdf

dextrose injection, solution Caution: Dextrose Injection is not for direct intravenous infusion. Prior to administration, Dextrose. Injection must be diluted with other compatible ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/020179s056lbl.pdf

dextrose injection - accessdata.fda.gov 10 OVERDOSAGE​​ An increased infusion rate of Dextrose Injection or administration of dextrose solutions can cause hyperglycemia, hyperosmolality, and adverse ...