The effect of diflunisal on familial amyloidosis

• Research type

  Research Study

• Full title

  A randomized, double-blind, placebo-controlled, international multi-center trial of diflunisal on neurologic disease progression in 200 familial amyloid subjects

• IRAS ID

  39016

• Contact name

  Arie Stangou

• Sponsor organisation

  John L. Berk

• Eudract number

  2006-001066-16

• Clinicaltrials.gov Identifier

  NCT00294671

• Research summary

  Amyloidosis refers to a family of diseases induced by misfolded and/or misassembled proteins. Deposition of these proteins as soluble or insoluble cross Ç?-sheets disrupts vital organ function. Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant (genetic) form of the disease with variable penetrance. Amyloid formation in FAP is mediated by misfolding of mutated transthyretin, a transport protein primarily produced by the liver. Survival after disease onset is 5-15 years without intervention. Death is caused by complications of neuropathy, including malnutrition, infection, and cardiac arrhythmias. Gene replacement by liver transplantation is the only effective therapy at present. Recent reports indicate amyloid deposition may progress after liver transplantation, however, undermining the clinical benefits of this treatment. Oral medication capable of stabilizing tetrameric TTR and reventing amyloid fibril formation would be valuable to a) FAP patients anticipating disease onset (by kindred experience), b)patients attempting to avoid liver transplantation, and c) those ineligible for organ transplantation. fluisal represents the first well-characterized TTR tetramer-stabilizing agent with a low toxicity profile demonstrated over several decades of use. This trial seeks to determine whether fluisal is effective therapy for FAP.

• REC name

  East of England - Cambridge South Research Ethics Committee

• REC reference

  10/H0305/37

• Date of REC Opinion

  25 Aug 2010

• REC opinion

  Further Information Favourable Opinion