High-Dose Vitamin C for Liver Transplant Care

(PARTI Trial)

Overseen By Helen Akere

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Wisconsin, Madison

Must not be taking: Vitamin C supplements

Disqualifiers: Pregnancy, Prisoner, Encephalopathy, Nephrolithiasis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether high doses of vitamin C (ascorbic acid) can aid recovery in liver transplant recipients. Some participants will receive vitamin C through an IV, while others will receive a placebo (a treatment with no active ingredient) for comparison. Researchers aim to determine if vitamin C affects organ function and survival rates after the transplant. Individuals scheduled for their first liver transplant from a deceased donor, without certain health conditions or restrictions, may qualify for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how vitamin C can further benefit patients post-transplant.

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 is the safety track record for these treatments?

Research has shown that vitamin C is generally safe, even in very high amounts. In some studies, participants received vitamin C through an IV (a method of delivering medicine directly into the bloodstream) at doses up to 50 mg per kilogram of body weight without harmful side effects. This indicates that high doses of vitamin C are usually well-tolerated.

Regarding liver transplants, vitamin C might offer additional benefits. Although more research is needed to fully understand its effects, early studies have shown positive results. This can reassure those considering participation in a trial involving high-dose vitamin C. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about high-dose vitamin C, or ascorbic acid (AA), for liver transplant care because it offers a novel approach compared to standard immunosuppressive therapies. Unlike traditional treatments that focus on dampening the immune response to prevent organ rejection, high-dose vitamin C might reduce inflammation and oxidative stress, which are critical during and after the transplant surgery. This antioxidant effect could potentially lead to better transplant outcomes and faster recovery times. By targeting inflammation more directly, this treatment may offer additional protection for the liver, potentially improving the overall success rate of liver transplants.

What evidence suggests that high-dose vitamin C might be an effective treatment for liver transplant care?

Research shows that high doses of vitamin C, administered through an IV, might aid patients after liver transplants. In this trial, some participants will receive Ascorbic Acid (AA), the active form of vitamin C, to evaluate its effects. One study found that vitamin C helped maintain steady blood flow and blood pressure during surgery. Another study showed that animals given vitamin C had lower liver enzyme levels and less swelling after liver surgery, suggesting it may protect the liver during these procedures. Overall, vitamin C has demonstrated positive effects in some transplant situations, prompting its testing for liver transplants in this trial. ^{1 2 3 6 7}

Who Is on the Research Team?

Molly Groose, MD, MS

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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

You are allergic to AA.

Current enrollment in another research study

I have G6PD deficiency.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbic acid
• Placebo

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in European Union as Vitamin C for:

• Scurvy
• Dietary supplement

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12306706/

A randomized trial of ascorbic acid for the prevention ... Conclusions: AA supplementation demonstrated a noticeable trend toward reducing PRS during liver transplantation, although this was not ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10757222/

Intravenous Ascorbic Acid for the Prevention of ... This study aims to show if ascorbic acid could be useful in preventing PRS during liver transplantation. Improved hemodynamic stability ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0261561422001169

Narrative Review Ascorbic acid in solid organ transplantation We believe that this study could be particularly relevant because it will be the first to analyze the clinical effect of ascorbic acid in liver transplantation.

4. withpower.com withpower.com/trial/high-dose-vitamin-c-for-liver-transplant-care-44fb3

High-Dose Vitamin C for Liver Transplant Care (PARTI Trial) 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.

5. mdpi.com mdpi.com/1422-0067/25/16/8833

The Effect of Ascorbic Acid on Hepatic Ischaemia– ... Animals receiving ascorbic acid before both ischaemia and reperfusion had lower liver enzyme levels, reduced inflammation, and better portal ...

6. researchprotocols.org researchprotocols.org/2023/1/e50091/

Intravenous Ascorbic Acid for the Prevention of ... The aim of this randomized controlled trial is to assess the benefits of ascorbic acid over saline in the development of PRS in adult liver transplantation.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01250743

A Pilot Study of High-Dose, Intravenous Ascorbic Acid ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...