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.
- Age 18 to 75 years
- Biopsy proven amyloidosis
- Genotyping of variant transthyretin
- Signs of peripheral or autonomic neuropathy
- Use of other non-steroidal anti-inflammatory drugs
- Other causes of sensorimotor polyneuropathy
- Anticipated survival <2 years or liver transplantation in <1 yr
- Liver transplantation
- Profound nerve, heart or kidney impairment
- Pregnancy or unwillingness to use contraception by women of childbearing age
- Active or recent gastrointestinal bleeding
- Non-steroidal or aspirin drug allergy/hypersensitivity
Last updated: 05/12/2013
NCT ID: NCT00294671