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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lactate, a natural energy source in the body, can reduce blood vessel damage in individuals at high risk for heart disease. It compares the effectiveness of lactate alone versus its combination with ischemic preconditioning (briefly stopping and starting blood flow) in protecting blood vessels. The trial also examines if combining lactate with ischemic preconditioning is more effective than using the technique alone. Suitable participants are those who have been mostly inactive, are not on heart-affecting medications, and have not recently smoked or used tobacco products. As an Early Phase 1 trial, this research aims to understand how lactate functions in people, offering participants a chance to contribute to groundbreaking heart disease research.

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.

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

Research has shown that administering lactate through an IV is generally safe for people. Studies with adults have reported no major side effects, indicating that the treatment is well-tolerated.

Ischemic preconditioning (IPC) is a method used to protect tissues from damage. Studies indicate that it is commonly used in medical practice and has a good safety record. Specifically, IPC has reduced the risk of complications during heart surgeries.

Research is exploring whether combining lactate with IPC offers optimal protection against injury. Although specific safety data for the combination is not detailed, both treatments alone are considered safe, which is promising for their combined use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for vascular injury because they explore the potential of intravenous lactate infusion to protect blood vessels from damage in a new way. Unlike traditional methods that often focus on ischemic preconditioning (IPC) alone, this study investigates whether lactate, a naturally occurring substance in the body, can offer similar or enhanced protective effects. The unique aspect is the combination of lactate with IPC, which could potentially boost the body's ability to shield blood vessels from ischemia/reperfusion injury more effectively than IPC alone. This could pave the way for more efficient and potentially quicker ways to manage vascular injuries.

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

This trial will compare the effects of ischemic preconditioning (IPC) and intravenous lactate infusion on reducing blood vessel damage caused by ischemia-reperfusion injury. Research has shown that IPC can reduce such damage, as demonstrated in studies involving both animals and humans. Early research also suggests that lactate, a natural substance in the body, might protect blood vessels during these injuries by enhancing protein function. Participants in this trial will be randomized to receive either IPC alone or an intravenous lactate infusion alone. Another group will receive a combination of IPC and lactate infusion to determine if this combination offers superior protection compared to either method alone. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06825143

Therapeutic Strategies to Reduce Endothelial Ischemia ... The objective of this Intervention is to show that an intravenous infusion of lactate protects against endothelial ischemia/reperfusion injury. Baseline ...

2. ctv.veeva.com ctv.veeva.com/study/therapeutic-strategies-to-reduce-endothelial-ischemia-reperfusion-injury

Therapeutic Strategies to Reduce Endothelial Ischemia ... The objective of this clinical trial is to better understand how lactate, a naturally occurring energy substance, can be used to lessen ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6208331/

In vitro Models of Ischemia-Reperfusion Injury - PMC Currently, there is no clinically relevant therapy available to reduce ischemia-reperfusion injury (IRI). While many drugs have shown promise in reducing IRI in ...

4. nature.com nature.com/articles/s41467-024-55589-w

Serpina3k lactylation protects from cardiac ischemia ... Lactate produced during ischemia-reperfusion injury is known to promote lactylation of proteins, which play controversial roles.

5. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.122.038466

Clinically Ineffective Reperfusion After Endovascular ... In recent RCTs and registry studies, successful reperfusion (mTICI score of 2b-3) was achieved in 80%–90% of acute LVO patients treated with EVT ...

6. withpower.com withpower.com/trial/early-phase-1-syndrome-9-2026-6bc3e

Lactate and Ischemic Preconditioning for Vascular Injury Research shows that intravenous lactate infusion is generally safe for humans, with no major side effects reported in studies involving adults with various ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8305209/

Brain Protection after Anoxic Brain Injury: Is Lactate ... In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury ...