A randomized clinical trial of oral vitamin A to reduce chronic graft versus host disease in BMT
Pooja Khandelwal
MDCincinnati Children’s Hospital Medical Center
Project Term: October 1, 2024 - September 30, 2027
Vitamin A is safe, well tolerated and positively affects gut immune health. Graft versus host disease (GVHD) is a life-threatening complication of bone marrow transplant (BMT) which happens due to inflammatory changes in the gut. We harnessed the anti-inflammatory properties of vitamin A by giving it to children before bone marrow transplant (BMT) and showed reduction in acute gut and moderate/severe chronic GVHD. We will validate our findings in this currently proposed study of an independent group of adult BMT patients. We will give vitamin A or placebo before BMT to adult BMT patients and observe for reduction of chronic GVHD in vitamin A recipients compared to placebo. This study will be a step forward in adoption of vitamin A as a universal strategy to prevent GVHD which is affordable ($1.25 for entire treatment), non-toxic, and doesn’t suppress the immune system.
Adult patients with underlying relapsed or difficult to treat leukemias undergo a bone marrow transplant (BMT) as a step towards cure, but about 30-50% develop a devastating complication called graft versus host disease (GVHD). Chronic GVHD affects multiple organs such as eyes, skin, joints and lungs, negatively impacts quality of life, reduces the ability to keep a job and requires medicines which suppress the immune system for treatment. Preventative treatments for chronic GVHD are limited. Vitamin A is a cheap, readily available, well tolerated, with powerful anti-inflammatory properties. Importantly, vitamin A doesn’t suppress the immune system. We will enroll adult cancer patients from 3 adult BMT programs in the United States and give them a single oral dose of vitamin A before they start BMT. Half of enrolled patients will receive vitamin A and the other half will get a placebo (canola oil). The determination of vitamin A or placebo will be randomly decided by a computer, half of patients will get either intervention. Patients, families, doctors and nurses will not be informed about which patient is getting vitamin A versus placebo until after the study is fully completed. When study is completed, we will reveal the treatment assignment and compare the incidence of chronic GVHD in patients who got vitamin A and placebo. We did a similar study in children and observed a reduction in moderate -severe chronic GVHD in children who got vitamin A when compared to placebo. The goal with this study is to validate our findings in adults, to ultimately make this a universal prevention strategy. The results from this study will be a step forward in identifying a way to prevent GVHD in patients with cancer who need to undergo a curative BMT. Avoiding chronic GVHD will allow cancer patients to recover after BMT without risk of infections, morbidity or death due to this life-threatening complication. Finally, vitamin A is an attractive strategy because 1) it has very few side effects 2) it is very cheap and can be used in countries all over the world 3) it is given as a single dose before BMT and is well tolerated 4) it does not suppress the immune system. Our research strategy of a randomized double-blinded placebo-controlled clinical trial is the best study design to answer our study question and has the greatest chance to be universally adopted if we can continue to show that vitamin A reduces the incidence of chronic GVHD in adult BMT patients. Patients will realize the benefit of this research within a year of getting vitamin A. Once our study is completed and successful, patients across the world can access this very easy approach to prevent GVHD, with profound and far reaching impact and benefits.