The Effect of Diflunisal on Familial Amyloidosis

NCT00294671 | Completed Phase 2 Results DMC

• 2 other identifiers: R01NS051306FD R 002532
• Study Type: interventional
• Target: 130
• Locations: 5 countries
• Sites: 8

Brief 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 Office of Orphan Products Development (OOPD); National Institute of Neurological Disorders and Stroke (NINDS)

Conditions

Familial Amyloid Polyneuropathy; Familial Amyloidosis

Keywords

familial amyloid polyneuropathy; familial amyloidosis; diflunisal; amyloidosis; transthyretin; peripheral neuropathy; autonomic neuropathy; amyloid cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• Neurologic Impairment Score + 7 (NIS+7)

  The primary endpoint, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurologic deficits) to 270 points (no detectable peripheral nerve function).

  Baseline, 1 and 2 years

Secondary Outcomes (4)

• Kumamoto Neurologic Scale;

  Baseline, 1 and 2 years

• Modified Body Mass Index (mBMI);

  Baseline, 1 and 2 years

• Quality of Life Questionnaire: SF-36 Physical Component Score

  Baseline, 1 and 2 years

• Quality of Life Questionnaire: SF-36 Mental Component Score

  Baseline, 1 and 2 years

Study Arms (2)

Diflunisal

ACTIVE COMPARATOR

Diflunisal 250 mg po bid

Drug: diflunisal

Placebo

PLACEBO COMPARATOR

Placebo 1 po bid

Other: placebo

Interventions

diflunisal DRUG

given twice daily for 24 months

Diflunisal

placebo OTHER

an inactive substance given twice daily for 24 months

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston University: lead
• Food and Drug Administration (FDA): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (8)

Amyloidosis Center, Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Mount Sinai School of Medicine, Department of Medicine

New York, New York, 10029-6574, United States

Location

IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Kumamoto University

Kumamoto, 860-0811, Japan

Location

Shinshu University

Matsumoto, 390-8621, Japan

Location

Umea University Hospital

Umeå, SE-901 86, Sweden

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24368466 DERIVED

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis, Familial; Amyloidosis; Peripheral Nervous System Diseases

Interventions

Diflunisal

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Proteostasis Deficiencies

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. John L. Berk
• Organization: Amyloidosis Center, Boston Medical Center

jberk@bu.edu

617-638-4494

Study Officials

• John L. Berk, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2006
• First Posted: February 22, 2006
• Study Start: February 1, 2006
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 17, 2017
• Results First Posted: March 17, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2); GB (1); IT (1); US (3); SE (1)