Lactate and Ischemic Preconditioning for Vascular Injury

Overseen By Gary P Van Guilder, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Gary Van Guilder

Must not be taking: Cardiovascular drugs, Oral contraceptives

Disqualifiers: Diabetes, Obesity, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

68 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this clinical trial is to better understand how lactate, a naturally occurring energy substance, can be used to lessen damage to the vascular system in adults with a high cardiovascular disease risk. The main questions it aims to answer are: 1. Does giving lactate intravenously reduce injury to the vascular system? 2. Does giving lactate intravenously together with blood flow occlusion - known as ischemic preconditioning, reduce vascular injury better than blood flow occlusion by itself? 3. How does lactate help the vascular system? Researchers will compare lactate to a placebo (a look-alike substance that contains no lactate) to see if lactate works to lessen vascular injury. Researchers will also compare lactate to blood flow occlusion to see which one is better at preventing vascular injury. Researchers will also compare lactate and blood flow occlusion together to see if combining them works better than either one alone. In one visit to the laboratory, participants will: Obtain a measurement of vascular health in an arm Be given liquid lactate, a liquid placebo, and/or arm blood flow occlusion Obtain a second measurement of vascular health in an arm.

Will I have to stop taking my current medications?

Yes, if you are using medications known to affect cardiovascular function, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the treatment Intravenous Lactate Infusion, Ischemic Preconditioning for vascular injury?

Research shows that lactate can protect against brain damage after a stroke in mice, and ischemic preconditioning can help prevent low blood pressure during dialysis. These findings suggest potential benefits of the treatment for vascular injury. ^{1 2 3 4 5}

Is intravenous lactate infusion safe for humans?

Research shows that intravenous lactate infusion is generally safe for humans, with no major side effects reported in studies involving adults with various conditions like diabetes, brain injury, and heart disease. ^{2 3 6 7 8}

How does the treatment Intravenous Lactate Infusion differ from other treatments for vascular injury?

Intravenous Lactate Infusion is unique because it involves directly administering lactate into the bloodstream, which may help protect blood vessels from damage by mimicking the body's natural response to low oxygen levels, a process known as ischemic preconditioning. This approach is different from other treatments that might not use lactate or focus on different mechanisms to protect against vascular injury. ^{3 9 10 11 12}

Eligibility Criteria

Adults at high risk for cardiovascular disease who may have conditions like Arterial Tortuosity Syndrome or Metabolic Syndrome. Participants should not have any health issues that could interfere with the trial, such as severe bleeding disorders or recent heart attacks.

Inclusion Criteria

Diet and weight stable for the past 3 months

Non-smoking and not using tobacco or electronic cigarettes

Exclusion Criteria

Metabolic acidosis

Body mass index greater than or equal to 35

Currently pregnant, recent pregnancy, or breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous lactate, placebo, and/or ischemic preconditioning to assess vascular health

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Intravenous Lactate Infusion
• Ischemic Preconditioning

Trial Overview The trial is testing if intravenous lactate can reduce vascular injury compared to a saline placebo and whether combining lactate with ischemic preconditioning (blood flow occlusion) offers greater protection than either treatment alone.

Participant Groups

Group I: Ischemic preconditioning combined with an intravenous lactate infusion Experimental Treatment 2 Interventions

To goal of this Arm is to compare the capacity of ischemic preconditioning (IPC) combined with an intravenous lactate infusion to protect against endothelial ischemia/reperfusion injury to IPC by itself. To achieve this goal, investigators will test the hypothesis that the capacity to protect against endothelial injury will be better when IPC and lactate are combined compared to IPC alone. Participants will be randomized to one of two Interventions. One Intervention will be the IPC intervention by itself. The other intervention will be adding an intravenous lactate infusion together with IPC which is the main focus of the study.

Group II: Ischemic preconditioning versus intravenous lactate infusion Active Control 4 Interventions

To goal of this Arm is to compare the capacity of ischemic preconditioning (IPC) to protect against endothelial ischemia/reperfusion injury to the capacity of an intravenous lactate infusion to protect against endothelial ischemia/reperfusion injury. To achieve this goal, investigators will test the hypothesis that the capacity for intravenous lactate to reduce endothelial injury will be equivalent to that of IPC. Participants will be randomized to one of two Interventions. One Intervention will be the IPC intervention which is thought to be effective in treating the condition under study. The other intervention is the intravenous lactate intervention, which is the main focus of the study.

Who Is Running the Clinical Trial?

Gary Van Guilder

Lead Sponsor

Trials

2

Recruited

90+

References

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

Myocardial lactate production is not involved in the ischemic preconditioning mechanism in coronary artery bypass graft surgery patients. [2013]

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

Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Application Value of Limb Ischemic Preconditioning in Preventing Intradialytic Hypotension during Maintenance Hemodialysis. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration. [2013]

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

Clinical significance of lactate in acute cardiac patients. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Lactate infusion as therapeutical intervention: a scoping review. [2023]

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

Endotoxin-induced hyperlactatemia results from decreased lactate clearance in hemodynamically stable rats. [2019]

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

Effects of lactate on the voltage-gated sodium channels of rat skeletal muscle: modulating current opinion. [2013]

9. China pubmed.ncbi.nlm.nih.gov

Endogenous nitric oxide mediates lipoteichoic acid induced preconditioning on reoxygenation injury of cultured human coronary artery endothelial cells. [2013]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Acute effects of glibenclamide on reactive hyperaemia in the lower limbs in humans. [2013]

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

Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption. [2020]

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

Ischemic preconditioning prevents postischemic arteriolar, capillary, and postcapillary venular dysfunction: signaling pathways mediating the adaptive metamorphosis to a protected phenotype in preconditioned endothelium. [2007]