Clinical trial NCT01956864: Study of High-Dose Oral Vitamin D for the Prevention of Liver Cancer
Official title: A Phase I Study of High-Dose Oral Vitamin D for the Prevention of Hepatocellular Carcinoma in Subjects With Cirrhosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Cirrhosis
Hepatocellular Carcinoma
Keywords: Vitamin D
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: M.D. Anderson Cancer Center
First posted: 2013-10-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the safety and tolerability of a high dose of vitamin D (VD) in patients with cirrhosis. The investigator hypothesizes that high dose VD will be safe and well-tolerated in adults with cirrhosis, and will inhibit the inflammatory and proliferative events that cause progression of cirrhosis to hepatocellular carcinoma.

Detailed description: This study will be done in two phases. The first phase is being done to find the highest dose of VD that can be tolerated, in other words taken without causing severe side effects. The second phase is a 6 month treatment with the dose determined to be safe in the first phase, to investigate general health benefits and the potential to reduce the development of Hepatocellular carcinoma (HCC), also known as liver cancer. Improvement of general health will be determined by interviews with patients, markers in the blood for response to VD, bone remodeling, inflammation, and evidence of HCC on routine imaging.

Eligibility criteria: Inclusion Criteria:

1. All subjects between the ages of 18 and 75 with cirrhosis of any etiology followed at the Georgetown Transplant Institute, Washington, DC, will be offered entry into this study. The diagnosis of cirrhosis will be based on clinical, imaging or histological studies.
2. No evidence of HCC on entry imaging study ( if liver nodules are present, these should be classified as LIRADS 1-3 only).
3. Model for End Stage Liver Disease (MELD) score under 22 (a MELD score over 22 would predict a 3 month mortality rate of approximately 20%).
4. Not currently participating in another intervention study.
5. Not pregnant or lactating, and willing to use effective contraception during study period.
6. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
7. Ability to provide written informed consent according to national/local regulations

Exclusion Criteria:

1. Any diagnosis of kidney stones
2. A diagnosis of granulomatous diseases (e.g., sarcoidosis), active chronic fungal or mycobacterial infections (e.g., tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, berylliosis, or Wegener's granulomatosis) in the past 6 months
3. A diagnosis of hyperparathyroidism or other serious disturbance of calcium metabolism in the past 5 years
4. A diagnosis of severe kidney disease, e.g., chronic renal failure, in the past 6 months
5. A diagnosis of unexplained hypercalcemia in the past 6 months
6. Any diagnosis of osteoporosis with physician recommendation for treatment of low bone mass
7. A diagnosis of two or more low trauma fractures in the past 6 months
8. A diagnosis of a medical condition requiring treatment with VD (e.g., osteomalacia) in the past 6 months

Primary outcomes:
measure: Number of participants on high dose Vitamin D with adverse events
timeFrame: after 1 year
Secondary outcomes:
measure: Changes in the expression of serum and imaging biomarkers
timeFrame: After 6 months on vitamin D regimen
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital /Johns Hopkins University
state: District of Columbia
Study officials:
affiliation: Johns Hopkins University
name: Kirti Shetty, MD
role: PRINCIPAL_INVESTIGATOR
References: