Obeticholic Acid for Familial Adenomatous Polyposis

This trial tests whether obeticholic acid (OCA), a drug similar to a natural bile acid, can reduce the number of polyps in individuals with familial adenomatous polyposis (FAP). FAP is a genetic condition that significantly increases the risk of intestinal and colon cancer. Participants will receive either OCA or a placebo (a harmless pill with no active drug) to determine if OCA is safe and effective. Suitable candidates for this trial have FAP with polyps in the small bowel or colon and have not had active cancer for at least six months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take investigational agents, certain bile acid medications, clozapine, theophylline derivatives, tizanidine, warfarin, and some drugs that affect the liver. If you're on these, you must stop them at least 5 days before starting the trial.

Research has shown that obeticholic acid (OCA) is generally safe based on its use for other conditions. The FDA approved OCA for treating primary biliary cholangitis (PBC), a liver disease, at a lower dose, indicating that the drug's safety is well-understood at that dose.

Unlike the standard treatments for familial adenomatous polyposis, which often involve surgery and non-specific medications, Obeticholic Acid (OCA) offers a different approach. OCA works by activating the farnesoid X receptor (FXR), which is thought to play a role in controlling cell growth in the intestines. Researchers are excited about this mechanism because it targets the disease more directly at the cellular level, potentially reducing the formation of polyps without the need for invasive procedures. This innovative focus on FXR activation is what sets OCA apart from conventional therapies and fuels optimism for its effectiveness.

Research has shown that obeticholic acid (OCA) effectively treats primary biliary cholangitis (PBC), a liver disease, and the FDA has approved it for this purpose. In PBC, OCA helps reduce inflammation and the thickening and scarring of tissue. This trial will evaluate OCA for familial adenomatous polyposis (FAP). Although it is not yet known if OCA can reduce the number of polyps in people with FAP, its mechanism suggests potential benefits. OCA resembles a natural substance produced by the liver and interacts with a part of the intestine, which might help prevent cancer. While there is no direct evidence that it reduces polyps in FAP, its success in other conditions suggests it could be beneficial.¹³⁴⁶⁷