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The Effect of Diflunisal on Familial Transthyretin Amyloidosis (DFNS01)

This study has been completed.
Information provided by (Responsible Party):
Ole B Suhr, Professor, MD, PhD, Umeå University Identifier:
First received: September 9, 2011
Last updated: August 21, 2015
Last verified: August 2015

An ongoing trial of diflunisal has been closed for enrollment, thus, patients suitable for the study can no longer participate or receive treatment by diflunisal; and patients, who have participated in the trial can not continue their treatment. The investigators want to continue to monitor the effect of the drug on transthyretin (TTR) amyloidosis in an open label observational study.

Primary endpoint will be a composite score of the manifestations of the disease (Kumamoto scale) and secondary end points will be measurements of neurological impairment, heart involvement and nutritional status.

Condition Intervention
Drug: Diflunisal

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Diflunisal on Familial Transthyretin Amyloidosis: An Open Label Extension Study of "the Diflunisal Trial" (IND 68092), and an Open Label Observational Study on Previously Untreated Patients With Familial Transthyretin Amyloidosis.

Resource links provided by NLM:

Further study details as provided by Ole B Suhr, Professor, MD, PhD, Umeå University:

Primary Outcome Measures:
  • Changes in the Kumamoto scale [ Time Frame: Enrollment, 12 month and annual follow-up ]
    Composite score of the manifestations of the disease (Kumamoto Scale). Results at enrollment will be compared to results at 12 months and annual follow-ups.

Secondary Outcome Measures:
  • Changes in modified body mass index (mBMI) [ Time Frame: Enrollment, 12 month and annual follow-up ]
    Changes in nutritional status measured by mBMI.Results at enrollment will be compared to results at 12 months and annual follow-ups.

  • Changes in paraneoplastic neurological disorders (PND) scale [ Time Frame: Enrollment, 12 month and annual follow-up ]
    Neurological impairment measured by the PND-score. Results at enrollment will be compared to results at 12 months and annual follow-ups.

  • Changes in cardiac function [ Time Frame: Enrollment, 1 month, 2 month, 3 month, 6 month, 9 month 12 month, 18 month and annual follow-up ]
    Cardiac impairment is measure by echocardiographic measurement of septal thickness and by proBNP in blood samples. Results at enrollment will be compared to results during the study and annual follow-ups.

  • Safety follow-up Blood Work [ Time Frame: 1 month, 3 month, 6 month, 9 month, 12 month and follow-up every 6 months ]
    To follow-up the patient safety during the study and follow-up the blood samples for (B-Hb), blood platelets, s-creatinine, liver enzymes [aspartate transaminase (ASAT),alanine aminotransferase (ALAT), s-bilirubin and alkaline phosphatase (ALP)],serum proBNP (S-proBNP) are drawn. Results at enrollment will be compares to results during study and every 6-month follow-ups.

Biospecimen Retention:   Samples Without DNA
Serum Whole blood Urine

Enrollment: 55
Study Start Date: August 2011
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Diflunisal
    Film-coated tablet, 250 mg twice daily, orally for approximately 2 years
Detailed Description:
Duration of treatment in this study is dependent of the results from the ongoing IND 68092-study, which are planned to be presented 2013.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients visiting the Units for Familal amyloidosis in Umeå, Piteå and Skellefteå

Inclusion Criteria:

  • Biopsy and genetically proven systemic transthyretin amyloidosis caused by a TTR gene mutation. The amyloid shall be proven to be of transthyretin type, and the fibril composition settled.
  • Age ≥ 18 years.
  • Negative pregnancy test and contraception for sexually active women of child bearing potential.

Exclusion Criteria:

  • Concomitant use of non-study non-steroidal anti-inflammatory drugs (NSAIDs)
  • Heart failure with symptoms at daily activities (NYHA class ≥III)
  • Renal insufficiency (creatinine clearance < 30 ml calculated from the Cockcroft-Gault formula)
  • Active non-haemorrhoidal bleeding within the last 18 month.
  • Non-treated peptic ulcer disease.
  • Anticoagulation therapy, low dose ASA permitted.
  • Non-steroidal or aspirin allergy/hypersensitivity
  • Thrombocytopenia (< 100,000 platelets/mm3)
  • Inability or unwillingness of subject to give written informed consent
  • By the investigator regarded as unable to follow the study guidelines and scheduled controls.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01432587

Dept of Clinical Medicin, Ptieå Hospital
Piteå, Sweden, SE-941 28
Dept of clinical medicin, Skellefteå Hospital
Skellefteå, Sweden, SE-931 86
Dept of Clinical Medicine, Umeå University Hospital
Umeå, Sweden, SE-90185
Sponsors and Collaborators
Umeå University
Principal Investigator: Ole B Suhr, MD PhD Dept of Clinical Medicine and public Health, Umeå University
  More Information

Responsible Party: Ole B Suhr, Professor, MD, PhD, Professor MD PhD, Umeå University Identifier: NCT01432587     History of Changes
Other Study ID Numbers: DFNS01
2011-000776-34 ( EudraCT Number )
Study First Received: September 9, 2011
Last Updated: August 21, 2015

Keywords provided by Ole B Suhr, Professor, MD, PhD, Umeå University:

Additional relevant MeSH terms:
Amyloid Neuropathies, Familial
Amyloid Neuropathies
Amyloidosis, Familial
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2017