The Effect of Diflunisal on Familial Amyloidosis

Familial Amyloid Polyneuropathy Clinical Trial

Official title:

The Effect of Diflunisal on Familial Amyloidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00294671
• Other study ID #: R01NS051306
• Secondary ID: FD R 002532R01NS
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 21, 2006
• Last updated: May 12, 2013
• Start date: February 2006
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloid Neuropathies
• Amyloid Neuropathies, Familial
• Amyloidosis
• Amyloidosis, Familial
• Familial Amyloid Polyneuropathy
• Familial Amyloidosis
• Polyneuropathies

Intervention

Drug:
• diflunisal
given twice daily for 24 months

Other:
• placebo
an inactive substance given twice daily for 24 months

Locations

Country	Name	City	State
Italy	IRCCS Policlinico San Matteo	Pavia
Japan	Kumamoto University	Kumamoto
Japan	Shinshu University	Matsumoto
Sweden	Umea University Hospital	Umea
United Kingdom	King's College Hospital	London
United States	Amyloid Treatment and Research Program, Boston Medical Center	Boston	Massachusetts
United States	Mount Sinai School of Medicine, Department of Medicine	New York	New York
United States	Mayo Clinic Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Boston University	Food and Drug Administration (FDA), National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Italy,  Japan,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurologic Impairment Score + 7 (NIS+7)		at 12 & 24 months	No
Secondary	Kumamoto neurologic scale;		at 6, 12 & 24 months	No
Secondary	Echocardiographic signs of cardiomyopathy;		at 12 & 24 months	No
Secondary	Modified body mass index ;		at 6, 12 & 24 months	No
Secondary	Amyloid burden ;		at 12 & 24 months	No
Secondary	Quality of life questionnaire		at 6, 12 & 24 months	No