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The Effect of Diflunisal on Familial Amyloidosis

This study has been completed.
Food and Drug Administration (FDA)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
John L. Berk, Boston University Identifier:
First received: February 21, 2006
Last updated: May 12, 2013
Last verified: May 2013

February 21, 2006
May 12, 2013
February 2006
December 2012   (Final data collection date for primary outcome measure)
Neurologic Impairment Score + 7 (NIS+7) [ Time Frame: at 12 & 24 months ]
Neurologic Impairment Score + 7 (NIS+7) at 12 & 24 months
Complete list of historical versions of study NCT00294671 on Archive Site
  • Kumamoto neurologic scale; [ Time Frame: at 6, 12 & 24 months ]
  • Echocardiographic signs of cardiomyopathy; [ Time Frame: at 12 & 24 months ]
  • Modified body mass index ; [ Time Frame: at 6, 12 & 24 months ]
  • Amyloid burden ; [ Time Frame: at 12 & 24 months ]
  • Quality of life questionnaire [ Time Frame: at 6, 12 & 24 months ]
  • Kumamoto neurologic scale at 6, 12 & 24 months;
  • Echocardiographic signs of cardiomyopathy at 12 & 24 months;
  • Modified body mass index at 6, 12 & 24 months;
  • Amyloid burden at 12 & 24 months;
  • Quality of life questionnaire at 6, 12 & 24 months
Not Provided
Not Provided
The Effect of Diflunisal on Familial Amyloidosis
The Effect of Diflunisal on Familial Amyloidosis

The purpose of this study is to determine if diflunisal can prevent progressive lower leg nerve damage in patients with familial amyloidosis polyneuropathy.

Funding Source - FDA OOPD; NINDS

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.

Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Familial Amyloid Polyneuropathy
  • Familial Amyloidosis
  • Drug: diflunisal
    given twice daily for 24 months
  • Other: placebo
    an inactive substance given twice daily for 24 months
  • Active Comparator: 1
    Intervention: Drug: diflunisal
  • Placebo Comparator: 2
    Intervention: Other: placebo
Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, Gorevic PD, Litchy WJ, Wiesman JF, Nordh E, Corato M, Lozza A, Cortese A, Robinson-Papp J, Colton T, Rybin DV, Bisbee AB, Ando Y, Ikeda S, Seldin DC, Merlini G, Skinner M, Kelly JW, Dyck PJ; Diflunisal Trial Consortium.. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013 Dec 25;310(24):2658-67. doi: 10.1001/jama.2013.283815.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2012
December 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 18 to 75 years
  • Biopsy proven amyloidosis
  • Genotyping of variant transthyretin
  • Signs of peripheral or autonomic neuropathy

Exclusion Criteria:

  • 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
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States,   Italy,   Japan,   Sweden,   United Kingdom
R01NS051306, FD R 002532, R01NS051306
Not Provided
Not Provided
Not Provided
John L. Berk, Boston University
Boston University
  • Food and Drug Administration (FDA)
  • National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: John L. Berk, MD Boston University
Boston University
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP