The Effect of Diflunisal on Familial Transthyretin Amyloidosis (DFNS01)

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.

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.

Study Overview

• Status: Completed
• Conditions: Amyloidosis
• Intervention / Treatment: Drug: Diflunisal

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.

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Sweden
  • Piteå, Sweden, SE-941 28
    • Dept of Clinical Medicin, Ptieå Hospital
  • Skellefteå, Sweden, SE-931 86
    • Dept of clinical medicin, Skellefteå Hospital
  • Umeå, Sweden, SE-90185
    • Dept of Clinical Medicine, Umeå University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients visiting the Units for Familal amyloidosis in Umeå, Piteå and Skellefteå

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Kumamoto scale	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.	Enrollment, 12 month and annual follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in modified body mass index (mBMI)	Changes in nutritional status measured by mBMI.Results at enrollment will be compared to results at 12 months and annual follow-ups.	Enrollment, 12 month and annual follow-up
Changes in paraneoplastic neurological disorders (PND) scale	Neurological impairment measured by the PND-score. Results at enrollment will be compared to results at 12 months and annual follow-ups.	Enrollment, 12 month and annual follow-up
Changes in cardiac function	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.	Enrollment, 1 month, 2 month, 3 month, 6 month, 9 month 12 month, 18 month and annual follow-up
Safety follow-up Blood Work	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.	1 month, 3 month, 6 month, 9 month, 12 month and follow-up every 6 months

Collaborators and Investigators

• Sponsor: Umeå University
• Investigators: Principal Investigator: Ole B Suhr, MD PhD, Dept of Clinical Medicine and public Health, Umeå University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 9, 2011
• First Submitted That Met QC Criteria: September 12, 2011
• First Posted (Estimate): September 13, 2011

Study Record Updates

• Last Update Posted (Estimate): August 24, 2015
• Last Update Submitted That Met QC Criteria: August 21, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Amyloidosis; Familial; Transthyretin; Neuropathies; Diflunisal
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diflunisal
• Other Study ID Numbers: DFNS01; 2011-000776-34 (EudraCT Number)