The Effect of Diflunisal on Familial Amyloidosis

• Neurologic Impairment Score + 7 (NIS+7) [ Time Frame: at 12 & 24 months ] [ Designated as safety issue: No ]
  

• Kumamoto neurologic scale; [ Time Frame: at 6, 12 & 24 months ] [ Designated as safety issue: No ]
  
• Echocardiographic signs of cardiomyopathy; [ Time Frame: at 12 & 24 months ] [ Designated as safety issue: No ]
  
• Modified body mass index ; [ Time Frame: at 6, 12 & 24 months ] [ Designated as safety issue: No ]
  
• Amyloid burden ; [ Time Frame: at 12 & 24 months ] [ Designated as safety issue: No ]
  
• Quality of life questionnaire [ Time Frame: at 6, 12 & 24 months ] [ Designated as safety issue: No ]
  

Familial amyloidosis polyneuropathy (FAP) is a rare, lethal, autosomal dominant, neurodegenerative disease characterized by misfolding of variant transthyretin tetramer (TTR) — a transport protein produced by the liver. The disease causes TTR to become unstable, triggering amyloid fibrils to form and leading to peripheral and autonomic nerve dysfunction.

Currently, the only treatment for FAP is a liver transplant, which is expensive and risk-filled. Medicines are needed to treat this disease. Previous in vitro (in a test tube) studies have shown that a common anti-inflammatory drug called diflunisal stabilizes TTR, preventing the formation of amyloid fibrils.

The goal of this 2-year randomized, double-blind, placebo-controlled research study is to establish whether diflunisal can stop the nerve damage, or peripheral neuropathy, resulting from amyloid production in patients with FAP. Scientists already know that diflunisal prevents formation of amyloid in the test tube. This study will determine if the drug can block amyloid production in FAP patients.

Participants will be randomly chosen to receive either diflunisal or an inactive (placebo) pill twice daily for 24 months. Participants will be carefully monitored through 7 follow-up visits, either at the study center or with individual primary care physicians. Participating in the study does not preclude patients from being listed for liver transplantation.