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Compensation: Varies

Number of Visits: 3

190 Participants Needed

Vitamin A for Graft-versus-Host Disease

Recruiting at 2 trial locations

Overseen ByCeleste 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 DataThis treatment has passed at least one previous human trial

Approved in 4 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a high dose of vitamin A can reduce moderate to severe chronic graft-versus-host disease (GVHD), a condition that may occur after a stem cell transplant. Participants will receive either a vitamin A supplement or a placebo pill. The trial targets individuals scheduled for an allogeneic stem cell transplant who have normal vitamin A levels and can take oral vitamins. The goal is to determine if vitamin A can prevent GVHD more effectively than not taking it. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that Vitamin A is likely to be safe for humans?

Research has shown that vitamin A is generally safe for people. In one study, none of the participants who took vitamin A developed acute gastrointestinal graft-versus-host disease (GVHD) by 180 days after their transplant, while 12.5% of those who took a placebo did. This suggests that vitamin A might be both effective and safe for people at risk of GVHD.

Another study found that fewer people in the vitamin A group (12.5%) experienced acute GVHD compared to the placebo group (20%). These results indicate that vitamin A does not cause major side effects, making it a potentially safe choice for those considering joining clinical trials to reduce GVHD.¹ ² ³ ⁴ ⁵

Why do researchers think this study treatment might be promising for GVHD?

Most treatments for graft-versus-host disease (GVHD) involve immunosuppressive drugs that aim to dampen the immune response. However, Vitamin A is unique because it might influence the immune system differently, potentially helping to regulate immune function more naturally. Researchers are excited about Vitamin A as it offers a novel approach by potentially reducing the severity of GVHD when administered before a transplant. This could lead to a safer and potentially more effective option for managing this challenging condition, with a simple oral administration method that's easy for patients to use.

What evidence suggests that vitamin A might be an effective treatment for graft-versus-host disease?

Research has shown that vitamin A, which participants in this trial may receive, might help lower the risk of graft-versus-host disease (GVHD), a condition where donor cells attack the recipient's body after a transplant. In one study, only 5% of people taking vitamin A developed chronic GVHD after one year, compared to 15% of those who took a placebo. Another study found that none of the participants taking vitamin A developed acute gastrointestinal GVHD, while 12.5% of those on a placebo did. These findings suggest that vitamin A could reduce the chances of developing GVHD by improving gut health and reducing inflammation. Overall, these studies provide promising evidence that vitamin A might be effective in lowering the risk of GVHD.¹ ² ³ ⁶ ⁷

Who Is on the Research Team?

Pooja Khandelwal, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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.

See 1 more

Exclusion Criteria

History of pregnancy

I have a history of increased pressure inside my skull.

I have a history of liver cirrhosis.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

2Treatment groups

Active Control

Placebo Group

Group I: Vitamin AActive Control1 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: PlaceboPlacebo Group1 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

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]

Citations

1.ashpublications.orgashpublications.org/blood/article/143/12/1181/514591/A-randomized-phase-2-trial-of-oral-vitamin-A-for

A randomized phase 2 trial of oral vitamin A for graft-versus ...Incidence of chronic GVHD was 5% in the vitamin A arm and 15% in the placebo arm (P = .02) at 1 year. In an “as treated” analysis, cumulative ...

2.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC5766846/

Lower levels of vitamin A are associated with increased ...We hypothesized that higher vitamin A levels would reduce the risk of graft-versus-host disease (GVHD) through reduced gastrointestinal (GI) permeability.

3.astctjournal.orgastctjournal.org/article/S1083-8791(16)30325-1/fulltext

Effects of Donor Vitamin A Deficiency and Pharmacologic ...In summary, our studies provide preclinical evidence that donor vitamin A deficiency may be a nongenetic factor that can modulate the severity of GVHD. Also, ...

4.ashpublications.orgashpublications.org/thehematologist/article/doi/10.1182/hem.V21.6.202466/518314/Vitamin-A-to-Keep-GVHD-Away-Single-Oral-High-Dose

Vitamin A to Keep GVHD Away: Single Oral High-Dose ...The cumulative incidence of acute GI GVHD by day 180 post-HSCT was 0% in the vitamin A arm and 12.5% in the placebo group (p=0.02; Figure), ...

5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38227933/

A randomized phase 2 trial of oral vitamin A for graft-versus ...Incidence of acute gastrointestinal (GI) GVHD was 2.5% in the vitamin A arm (P = .09) and 12.5% in the placebo arm at day +180. Incidence of ...

6.frontiersin.orgfrontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1225748/full

Graft-versus-host disease: teaching old drugs new tricks at ...Vitamin A prevents acute and chronic graft versus host disease in children and young adults: A single-center randomized double-blinded placebo-controlled ...

7.sciencedirect.comsciencedirect.com/science/article/pii/S2666636724004329

Cutaneous Chronic Graft-Versus-Host Disease: Clinical ...Topical retinoids may cause dryness and irritation but are likely safe to use. ... A1 phototherapy as a treatment for chronic cutaneous graft-versus-host disease.

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