The Effect of Diflunisal on Familial Transthyretin Amyloidosis

Amyloidosis Clinical Trial

— DFNS01  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01432587
• Other study ID #: DFNS01
• Secondary ID: 2011-000776-34
• Status: Completed
• Phase: N/A
• First received: September 9, 2011
• Last updated: August 21, 2015
• Start date: August 2011
• Est. completion date: December 2014

Study information

• Verified date: August 2015
• Source: Umeå University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis

Intervention

Drug:
• Diflunisal
Film-coated tablet, 250 mg twice daily, orally for approximately 2 years

Locations

Country	Name	City	State
Sweden	Dept of Clinical Medicin, Ptieå Hospital	Piteå
Sweden	Dept of clinical medicin, Skellefteå Hospital	Skellefteå
Sweden	Dept of Clinical Medicine, Umeå University Hospital	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
Umeå University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes