Clinical Trial: The Effect of Diflunisal on Familial Amyloidosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Effect of Diflunisal on Familial Amyloidosis

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)


Detailed Summary:

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.


Sponsor: Boston University

Current Primary Outcome: 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).


Original Primary Outcome: Neurologic Impairment Score + 7 (NIS+7) at 12 & 24 months

Current Secondary Outcome:

  • 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)
  • 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].
  • 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.
  • 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.


Original Secondary Outcome:

  • 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


Information By: Boston University

Dates:
Date Received: February 21, 2006
Date Started: February 2006
Date Completion:
Last Updated: January 30, 2017
Last Verified: January 2017