Amyloidosis
Conditions
Keywords
Amyloidosis, Transthyretin, Neuropathies, Diflunisal, Familial
Brief 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.
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.
Interventions
DRUGDiflunisal
Film-coated tablet, 250 mg twice daily, orally for approximately 2 years
Sponsors
Umeå University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Kumamoto scale | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in modified body mass index (mBMI) | 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 | 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 | 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 | 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. |
Countries
Sweden
Outcome results
None listed