Vitamin A for Graft-versus-Host Disease

Recruiting at 2 trial locations

Overseen By Celeste Dourson, MS, CCRP

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Raised intracranial pressure, liver cirrhosis, pregnancy

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

190 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that single oral high dose supplementation with vitamin A will reduce the incidence of moderate-severe chronic graft-versus-host disease (GVHD) compared with placebo.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Vitamin A for treating graft-versus-host disease?

Research suggests that Vitamin A, particularly its active form retinoic acid, may help regulate the immune system and reduce the severity of graft-versus-host disease (GVHD) by influencing immune cell behavior and reducing intestinal damage. Studies have shown that higher levels of Vitamin A are associated with a lower risk of gastrointestinal GVHD, indicating its potential benefit in managing this condition. ^{1 2 3 4 5}

Is Vitamin A safe for use in humans?

Vitamin A is generally considered safe for humans when used appropriately, but its deficiency or excess can affect health. In the context of graft-versus-host disease, studies suggest that low levels of Vitamin A may increase complications, while appropriate levels might improve outcomes. However, specific safety data for Vitamin A in this condition is limited, and it is important to follow medical guidance when considering its use. ^{1 2 3 5 6}

How does the drug Vitamin A differ from other treatments for graft-versus-host disease?

Vitamin A, specifically its active form retinoic acid, is unique in its ability to regulate the immune system, potentially reducing the severity of graft-versus-host disease by influencing immune cell behavior and reducing gastrointestinal complications. Unlike standard treatments, Vitamin A works by promoting mucosal tolerance and enhancing regulatory T cells, which may help improve transplant outcomes. ^{1 2 3 5 6}

Research Team

Pooja Khandelwal, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for people who are about to undergo a stem cell transplant, have lower than normal levels of Vitamin A, can take vitamins by mouth, and have liver function within certain limits. It's not for those with high brain pressure, pregnant individuals or anyone with liver cirrhosis.

Inclusion Criteria

Total bilirubin level < 1.5x ULN and AST and/or ALT < 3x ULN for age

I am scheduled for a stem cell transplant from a donor.

I can take vitamins by mouth without issues.

Exclusion Criteria

I have a history of increased pressure inside my skull.

History of pregnancy

I have a history of liver cirrhosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant

Participants receive a single oral high dose of vitamin A or placebo before transplantation

1 day

1 visit (in-person)

Post-transplant Monitoring

Vitamin A levels are measured pre-transplant and again at day +30

30 days

2 visits (in-person)

Follow-up

Participants are monitored for overall survival and incidence of GVHD and relapse

2 years

Treatment Details

Interventions

• Vitamin A

Trial Overview The study tests if taking a single high dose of Vitamin A orally can reduce the chances of developing moderate to severe chronic Graft-versus-Host Disease (GVHD) after a stem cell transplant compared to a placebo.

Participant Groups

Group I: Vitamin A Active Control 1 Intervention

Route of administration: Oral. Frequency: Once. Timing: Pre-transplant Dose of Vit A: 1.2 mg/kg, max dose 75 mg Formulation of Vit A: 2.5 mg liquid filled oral capsules. Vitamin A level assessment: Vitamin A levels will be measured pre-transplant and again at day +30 (± 10 days)

Group II: Placebo Placebo Group 1 Intervention

Placebo pills containing microcrystalline cellulose will be dispensed in patients who are randomized to the placebo arm.

Vitamin A is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Approved in European Union as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Approved in Canada as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

Chronic vitamin A deficiency in donor mice leads to a reduced percentage of CD4+ T cells, which is associated with a lower incidence and severity of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT).

Inhibiting the retinoic acid/retinoic acid receptor (RA/RAR) pathway in donor T cells can decrease their alloreactivity, suggesting that targeting this pathway may be a promising strategy to mitigate GVHD in patients undergoing HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Donor Vitamin A Deficiency and Pharmacologic Modulation of Donor T Cell Retinoic Acid Pathway on the Severity of Experimental Graft-versus-Host Disease. Dodge, J., Stephans, A., Lai, J., et al.[2018]

References

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

Role of Vitamin A in Modulating Graft-versus-Host Disease. [2020]

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

Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children. [2021]

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

Effects of Donor Vitamin A Deficiency and Pharmacologic Modulation of Donor T Cell Retinoic Acid Pathway on the Severity of Experimental Graft-versus-Host Disease. [2018]

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

Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Tretinoin for the treatment of cutaneous graft-versus-host disease. [2013]

6. China pubmed.ncbi.nlm.nih.gov

Vitamin D alleviates acute graft-versus-host disease through promoting the generation of Foxp3+ T cells. [2022]