High-Dose Vitamin C for Liver Transplant Care

(PARTI Trial)

Overseen by Molly Groose, MD, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Wisconsin, Madison

Must not be taking: Vitamin C supplements

Disqualifiers: Pregnancy, Prisoner, Encephalopathy, Nephrolithiasis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

A single-center, randomized, double-blinded placebo-controlled trial is proposed to investigate administration of supraphysiologic doses of ascorbic acid (vitamin C, AA) to patients undergoing liver transplantation. Participants randomized to the intervention group will receive intravenous (IV) AA 1500 mg every 6 hours for 48 hours. Participants randomized to the control group will receive a saline placebo. The primary study outcome will be a change in the Sequential Organ Failure Assessment (SOFA) score from baseline to three days after the first dose of drug (dSOFA3). Secondary outcomes will include total vasopressor dose in norepinephrine equivalents, 30-day and 1-year mortality, and serum AA levels.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking vitamin C supplements, you must stop them at least a month before participating.

What data supports the effectiveness of the treatment High-Dose Vitamin C for Liver Transplant Care?

Some studies suggest that high-dose vitamin C might help in other conditions like sepsis (a severe infection) and may have potential as an additional therapy, but there is no direct evidence supporting its effectiveness specifically for liver transplant care. ^{1 2 3 4 5}

How is high-dose vitamin C unique for liver transplant care?

High-dose vitamin C is unique for liver transplant care due to its antioxidant properties, which may help reduce oxidative stress and improve immune function, potentially aiding in recovery and reducing complications. Unlike standard treatments, it is being explored for its potential benefits in this specific context, although its efficacy is still under investigation. ^{3 5 6 7 8}

Research Team

Molly Groose, MD, MS

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adults set to have their first liver transplant from a deceased donor. It's not for prisoners, those with decision-making impairments, allergies to vitamin C, certain blood disorders like G6PD deficiency or sickle cell anemia, kidney issues including stones or high creatinine without dialysis, pregnant individuals, non-English speakers, or anyone on other trials.

Inclusion Criteria

I am scheduled for a liver transplant from a deceased donor.

Exclusion Criteria

I do not speak English.

You are allergic to AA.

Current enrollment in another research study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intravenous ascorbic acid or placebo every 6 hours for 48 hours during the perioperative period

2 days

In-hospital during liver transplantation

Follow-up

Participants are monitored for changes in SOFA scores and incidence of early graft dysfunction and infection

7 days

In-hospital monitoring

Long-term Follow-up

Participants are monitored for 30-day and 1-year mortality outcomes

1 year

Treatment Details

Interventions

• Ascorbic acid (Vitamin)
• Placebo (Other)

Trial Overview The study tests if high doses of vitamin C given through IV can help patients after liver transplants better than a saltwater placebo. Participants are randomly chosen to get either the vitamin C treatment every 6 hours for two days or the placebo. Doctors will check if there's any improvement in organ failure scores and monitor other health outcomes.

Participant Groups

Group I: Ascorbic Acid (AA) Experimental Treatment 1 Intervention

The first intravenous dosage of 1500mg of AA in 100mL of normal saline (NS) will be administered after induction of general anesthesia and invasive line placement prior to surgical incision. An identical dosage will be delivered approximately every 6 hours for the first 48 hours, for a total of 8 doses

Group II: Placebo Placebo Group 1 Intervention

The first intravenous dosage of placebo (100 mL of NS) will be administered after induction of general anesthesia and invasive line placement prior to surgical incision. An identical dosage will be delivered approximately every 6 hours for the first 48 hours, for a total of 8 doses

Ascorbic acid is already approved in Canada for the following indications:

Approved in Canada as Vitamin C for:

• Scurvy
• Dietary supplement

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Robert Drape

University of Wisconsin, Madison

Chief Executive Officer since 2007

Executive MBA from the University of Wisconsin – Madison, Bachelor's degree in Biology from Augustana College (IL)

Dr. Ciara Barclay-Buchanan

University of Wisconsin, Madison

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Findings from Research

A post hoc Bayesian reanalysis of the Lessening Organ Dysfunction with Vitamin C trial involving 872 ICU patients showed that vitamin C treatment increased the risk of death or persistent organ dysfunction at 28 days, with a risk ratio of 1.20 and a 99% probability of harm.

The analysis indicated that vitamin C was associated with a higher risk of death at 28 days, reinforcing the conclusion that vitamin C may be harmful for adults with infections requiring vasopressor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial. Angriman, F., Muttalib, F., Lamontagne, F., et al.[2023]

Surgical patients experience a significant drop in blood vitamin C levels post-surgery, necessitating higher doses than the standard recommendations, with over 500 mg/day suggested for uncomplicated surgeries and even higher for those in intensive care.

High-dose vitamin C supplementation has been linked to reduced oxidative stress and may prevent complications like postoperative atrial fibrillation, indicating its potential benefits in surgical recovery, though optimal dosing still needs further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C requirement in surgical patients. Fukushima, R., Yamazaki, E.[2022]

In a randomized double-blind controlled trial involving 175 cardiac surgery patients, taking 800 mg of vitamin C four times daily significantly increased plasma vitamin C levels compared to a placebo group.

However, despite the increase in vitamin C levels, there was no significant difference in the incidence of posttransfusion hepatitis or its clinical course between the vitamin C and placebo groups, suggesting that vitamin C does not prevent this type of infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C prophylaxis for posttransfusion hepatitis: lack of effect in a controlled trial. Knodell, RG., Tate, MA., Akl, BF., et al.[2018]

High-dose parenteral vitamin C shows promise as an adjuvant therapy for sepsis, as it can prevent or reverse harmful changes in blood vessels and reduce complications like hypotension and organ failure in animal models.

While high doses of vitamin C are generally well-tolerated in healthy individuals, the safety and potential adverse effects in critically ill patients remain uncertain, highlighting the need for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of vitamin C for adjuvant sepsis therapy. Wilson, JX.[2022]

Intravenous high-dose vitamin C (2.83 g/kg) significantly improved liver function in rats with implanted hepatoma, as indicated by higher albumin/globulin ratios and lower ALT levels compared to untreated rats.

The same dosage of vitamin C also increased tumor necrosis rates, suggesting it may promote the death of cancer cells while protecting liver function in the process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of intravenous high-dose vitamin C on implanted hepatoma in rats]. Peng, LJ., Lu, DX., Qi, RB., et al.[2013]

High-dose vitamin C interventions are gaining attention in clinical medicine due to their antioxidant properties and safety, but many randomized control trials lack proper analytical methods, leading to unreliable comparisons.

Switching from older testing methods to high performance liquid chromatography (HPLC) has significantly improved the accuracy and consistency of vitamin C measurements, making it suitable for high-dose vitamin C trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C measurement in critical illness: challenges, methodologies and quality improvements. Collie, JTB., Greaves, RF., Jones, OAH., et al.[2021]

In a 90-day study with rats, the combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) significantly reduced markers of liver damage and oxidative stress caused by ethanol, indicating their protective effects against hepatotoxicity.

The combination of AT and AA not only enhanced antioxidant enzyme activity but also led to a nearly 20% greater reduction in liver fibrosis compared to when each was administered alone, suggesting a synergistic effect in combating liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive effect of alpha-tocopherol and ascorbic acid in combating ethanol-induced hepatic fibrosis. Prathibha, P., Rejitha, S., Harikrishnan, R., et al.[2021]

In a study involving 15 healthy males, calcium ascorbate with vitamin C metabolites significantly increased vitamin C concentrations in leukocytes after 24 hours compared to vitamin C alone, indicating enhanced cellular utilization of vitamin C.

No significant differences in plasma vitamin C levels were found among the different formulations, suggesting that while metabolites may improve leukocyte uptake, they do not affect overall plasma levels, highlighting the need for further research on their impact on immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Moyad, MA., Combs, MA., Vrablic, AS., et al.[2013]

References

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

IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Vitamin C requirement in surgical patients. [2022]

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

Vitamin C prophylaxis for posttransfusion hepatitis: lack of effect in a controlled trial. [2018]

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

Evaluation of vitamin C for adjuvant sepsis therapy. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of intravenous high-dose vitamin C on implanted hepatoma in rats]. [2013]

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

Vitamin C measurement in critical illness: challenges, methodologies and quality improvements. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Additive effect of alpha-tocopherol and ascorbic acid in combating ethanol-induced hepatic fibrosis. [2021]

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

Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. [2013]