Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration
Status:
Completed
Trial end date:
2020-07-01
Target enrollment:
Participant gender:
Summary
Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid
secreted by the stomach. Some ranitidine medicines contain an impurity called
N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human
carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA
is a known environmental contaminant and found in water and foods, including meats, dairy
products, and vegetables.
The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine
products similar to the levels you would expect to be exposed to if you ate common foods like
grilled or smoked meats. The ranitidine that will be used in this study has been tested twice
(months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of
note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration
as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70
years of exposure to that level.
FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine
after it has been exposed to acid in the stomach with a normal diet. Results of these tests
indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is
exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory
experiments suggest a combination of nitrites, such as found in processed meats, and an
acidic environment may increase NDMA formation, however the levels of nitrites tested were
very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who
received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase
was greater than would be expected from laboratory testing.
This clinical study is being performed to determine if and how much NDMA is produced from
ranitidine in the human body and whether nitrite-containing foods may increase formation of
NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is
increased urinary NDMA excretion levels over 24-hours after ranitidine administration in
comparison to placebo when participants are administered low nitrite/NDMA meals and when
subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will
receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low
nitrite/NDMA meals.