The Effect of Diflunisal on Familial Transthyretin Amyloidosis - Full Text View

Purpose

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
Amyloidosis	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:

Genetics Home Reference related topics: transthyretin amyloidosis

MedlinePlus related topics: Amyloidosis

Drug Information available for: Diflunisal

Genetic and Rare Diseases Information Center resources: Familial Transthyretin Amyloidosis Amyloid Neuropathy

U.S. FDA Resources

Further study details as provided by Umeå University:

Primary Outcome Measures:

Changes in the Kumamoto scale [ Time Frame: Enrollment, 12 month and annual follow-up ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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:

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

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

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432587

Locations


Sweden
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

Investigators


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
ClinicalTrials.gov Identifier:	NCT01432587 History of Changes
Other Study ID Numbers:	DFNS01 2011-000776-34
Study First Received:	September 9, 2011
Last Updated:	August 21, 2015
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Umeå University:


Amyloidosis Transthyretin Neuropathies Diflunisal Familial

Additional relevant MeSH terms:


Amyloidosis Amyloid Neuropathies, Familial Proteostasis Deficiencies Metabolic Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Amyloid Neuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Genetic Diseases, Inborn Amyloidosis, Familial Metabolism, Inborn Errors	Diflunisal Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics 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

ClinicalTrials.gov processed this record on September 23, 2016

The Effect of Diflunisal on Familial Transthyretin Amyloidosis (DFNS01)