The Effect of Vitamin D Repletion in Patients With Hepatocellular Carcinoma on the Orthotopic Liver Transplant List

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of two different doses of vitamin D3 (2000 IU vs. 4000 IU) on serum 25-hydroxyvitamin D (25OHD) levels in patients with hepatocellular carcinoma on the liver transplant list. The study will help determine the dose of vitamin D3 that is required for patients with liver cancer to reach a normal level of 25OHD in the blood.

Detailed Description
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Potential participants will be identified from Mount Sinai Hospital's active liver transplant list. The hepatologists at Mount Sinai's Transplant Institute will ask each potential participant if she/he is interested in participating. If the patient expresses an interest in the study, one of the researchers will meet with the patient when the patient is at Mount Sinai for a regular appointment and will describe the study to the potential participant. If a patient continues to be interested in participating, she/he will be given a copy of the IRB-approved consent document to read. The consent document will be used as a guide for explaining the study in detail to the patient. If the patient's preferred language is Spanish, she/he will be given a consent document in Spanish and the study will be explained in Spanish. Once the subject's 25(OH)D level is known, if the subject's 25(OH)D level is ≤ 15 ng/ml, the participant will be contacted by one of the investigators on the research team and instructed to begin taking 2 tablets per day (4000 IU total) of vitamin D. If the subject's 25(OH)D level is greater than 15 and ≤ 25, the participant will be contacted by one of the investigators on the research team and told to begin taking 1 tablet (2000 IU total) per day of vitamin D. If the participant's vitamin D level is < 25 ng/ml, they are considered Vitamin D insufficient/deficient. If the Serum Vitamin D is > 25 ng/ml they will be informed that they are not to take any vitamin D and they will be followed as controls for this study.

Official Title
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The Effect of Vitamin D Repletion in Patients With Hepatocellular Carcinoma on the Orthotopic Liver Transplant List

Conditions
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Vitamin D Deficiency, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Vitamin D3 4000 IU
* Drug: Vitamin D3 2000 IU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18 years and older) Diagnosis of hepatocellular carcinoma On the list awaiting liver transplantation Able to give informed consent Expected to receive care following liver transplantation at the Mount Sinai School of Medicine Any race/ethnicity/socioeconomic status Exclusion Criteria: Pediatric patient (less than 18 years of age) Unable to give informed consent Untreated primary hyperparathyroidism (ICD9 codes 252.01XX and 252.00XX) Untreated hypercalcemia (serum calcium level > 11 mg/dl; ICD9 codes 275.42XX, 259.3XX, 252.00F) Pregnancy (will be determined by asking the patient and reviewing the medical record)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D 4000<br>Subjects taking 4000 IU of vitamin D | Drug: Vitamin D3 4000 IU<br>* Participants with serum 25-hydroxyvitamin D levels of less than or equal to 15ng/ml will take 4000 IU of vitamin D3 daily by mouth for 6 months<br>* Other names: Vitamin D 4000;|
| Experimental: Vitamin D 2000<br>Subjects taking 2000IU of vitamin D | Drug: Vitamin D3 2000 IU<br>* Participants with serum 25-hydroxyvitamin D levels of greater than 15 ng/ml and less than or equal to 25ng/ml will take 2000 IU of vitamin D3 daily by mouth for 6 months<br>* Other names: Vitamin D 2000;|
| No Intervention: No Intervention<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum levels of 25-hydroxyvitamin D | Change in serum levels of 25-hydroxyvitamin D at 3 months and 6 months compared to baseline | at baseline, and at 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum levels of liver enzymes (ALT, AST and Alk phos) | Change in serum levels of liver enzymes (ALT, AST and Alk phos) at 3 months and at 6 months compared to baseline | at baseline, and at 3 and 6 months | 
| Change in serum creatinine | Change in serum creatinine at 3 months and at 6 months compared to baseline | at baseline, and at 3 and 6 months | 
| Serum Calcium |  | at 3 months | 
| Serum Calcium |  | at 6 months | 
| Change in coagulation profile (PT/PTT and INR) | Change in coagulation profile (PT/PTT and INR) at 3 months and at 6 months compared to baseline | at baseline, and at 3 and 6 months | 
| Change in Model for End stage Liver Disease score (MELD) | Change in Model for End stage Liver Disease score (MELD) at 3 months and at 6 months compared to baseline. Calculated using the following formula: Meld = 10x ((0.957 x Ln(creatinine mg/dl)) + (0.378 x Ln(bilirubin mg/dl)) + (1.120 x Ln(INR)) + 0.643) | at baseline, and at 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, hepatocellular carcinoma, liver neoplasms, liver transplantation