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Completed

NCT Number: NCT00294671

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

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

IRCCS Policlinico San Matteo, Pavia, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

diflunisal

Drug

given twice daily for 24 months

Placebo

Other

an inactive substance given twice daily for 24 months

Primary outcomes

  1. Neurologic Impairment Score + 7 (NIS+7)

    Time frame: Baseline, 1 and 2 years

    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).

Secondary outcomes

  1. Kumamoto Neurologic Scale;

    Time frame: Baseline, 1 and 2 years

    Change from baseline of the Kumamoto Score (0-102 points, increasing with disease severity), a clinical neurologic scale of motor, sensory, and autonomic function combined with heart and kidney end organ measures developed to track disease progression in Familial Amyloid Polyneuropathy (ATTR-FAP)

  2. Modified Body Mass Index (mBMI);

    Time frame: Baseline, 1 and 2 years

    The product of body mass index (BMI) and serum albumin level (g/L) [kg/M2xg/L].

  3. Quality of Life Questionnaire: SF-36 Physical Component Score

    Time frame: Baseline, 1 and 2 years

    The 36 item short-form health survey (SF-36) was used to assess the difference between treatment groups for change of physical component scores over 2 years treatment. Range 0-100; lower scores reflect lower quality-of-life.

  4. Quality of Life Questionnaire: SF-36 Mental Component Score

    Time frame: Baseline, 1 and 2 years

    The 36 item short-form health survey (SF-36) was used to assess the difference between treatment groups for change of mental component scores over 2 years treatment. Range 0-100; lower scores reflect lower quality-of-life.

Sponsors and collaborators

Lead sponsor

Boston University

Other

Collaborators

  • Food and Drug Administration (FDA)
  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Important dates

Study start
2006
Primary completion
2012
Study completion
2012
First posted
Feb 22, 2006
Registry last updated
Mar 17, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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