The Effect of Diflunisal on Familial Amyloidosis
Information source: National Institute of Neurological Disorders and Stroke (NINDS)
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Familial Amyloid Polyneuropathy; Familial Amyloidosis
Intervention: diflunisal (Drug); placebo (Other)
Phase: Phase 2/Phase 3
Status: Recruiting
Sponsored by: Boston University Official(s) and/or principal investigator(s):
John L. Berk, MD, Principal Investigator, Affiliation: Boston University
Overall contact:
Melissa Rosenberg, Phone: 617-638-4494, Email: merose@bu.edu
Summary
The purpose of this study is to determine if diflunisal can prevent progressive lower leg
nerve damage in patients with familial amyloidosis polyneuropathy.
Clinical Details
Official title: The Effect of Diflunisal on Familial Amyloidosis
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Neurologic Impairment Score + 7 (NIS+7)
Secondary outcome: Kumamoto neurologic scale;Echocardiographic signs of cardiomyopathy; Modified body mass index ; Amyloid burden ; Quality of life questionnaire
Detailed 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age between 18 and 75 years
- Biopsy proven amyloidosis
- Genotyping of variant transthyretin
- Signs of mild to moderate peripheral 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
Locations and Contacts
Melissa Rosenberg, Phone: 617-638-4494, Email: merose@bu.edu
IRCCS Policlinico San Matteo, Pavia 27100, Italy; Recruiting
Laura Obici, MD, Phone: 39-0382-502-983, Email: l.obici@smatteo.pv.it
Kumamoto University, Kumamoto 860-0811, Japan; Recruiting
Taro Yamashita, MD, PhD, Phone: 096-373-5893, Email: taro-yamashita@fc.kuh.kumamoto-u.ac.jp
Shinshu University, Matsumoto 390-8621, Japan; Recruiting
Yoshi Sekijima, MD, Phone: 81-263-37-2673, Email: sekijima@hsp.md.shinshu-u.ac.jp
Hospital Santo Antonio, Porto 4099-001, Portugal; Not yet recruiting
Teresa Coelho, MD, Phone: 351-91-8840370, Email: tcoelho@netcabo.pt
Umea University Hospital, Umea SE-901 86, Sweden; Recruiting
Hans Eric, MD, Phone: 46 90 785 1415, Email: HansErik.Lundgren@vll.se
The Scripps Research Institute, La Jolla, California 92035, United States; Not yet recruiting
Amyloid Treatment and Research Program, Boston Medical Center, Boston, Massachusetts 02118, United States; Recruiting
Melissa Rosenberg, Phone: 617-638-4494, Email: merose@bu.edu
Mayo Clinic Rochester, Rochester, Minnesota 55905, United States; Recruiting
Steven Zeldenrust, MD, PhD, Phone: 507-284-2865, Email: zeldenrust.steven@mayo.edu
Additional Information
Starting date: February 2006
Ending date: August 2010
Last updated: June 6, 2008
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