Familial transthyretin amyloidosis complicated by cardiomyopathy MedDRA version: 18.0 Level: LLT Classification code 10019893 Term: Hereditary neuropathic amyloidosis, Swedish type System Organ Class: 100000004850
Conditions
Interventions
Pharmaceutical Form: Film-coated tablet
Sponsors
Umeå University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Open to patients that have been participating in the DFNS01 study. All patients will have a 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. For patients not previously participating in the DFNS01 trial, the diagnosis shall be proven by biopsy and identification of a TTR-gene mutation. The amyloid shall be proven to be of transthyretin type, and the fibril composition settled. TTTR-amyloid cardiomyopathy shall be confirmed by DPD-scintigraphy, and an increased intra-ventricular septal thickness of > 12 mm and a pro-BNP blood concentration above the normal limit. 2. Age = 18 years. 3. Negative pregnancy test for sexually active women of child bearing potential and willing to comply with effective contraception methods during the course of the trial. Acceptable methods are such as oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double-barrier methods (for example, condom and spermicide), intrauterine device (IUD), hormonal IUD. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Concomitant use of non-study NSAIDs 2. Heart failure with symptoms at daily activities (NYHA class =III) 3. Renal insufficiency (creatinine clearence < 30 ml calculated from the Cockcroft-Gault formula) 4. Active non-haemorrhoidal bleeding within the last 18 month. 5. Non-treated peptic ulcer disease. 6. Anticoagulation therapy, low dose ASA permitted (=160 mg). 7. Non-steroidal or aspirin allergy/hypersensitivity 8. Thrombocytopenia (< 100,000 platelets/mm3) 9. Inability or unwillingness of subject to give written informed consent 10. By the investigator regarded as unable to follow the study guidelines and scheduled controls.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To follow the development of neurological, nutritional and cardiac manifestations of transthyretin amyloidosis in patients treated by Diflunisal 250 mg twice daily. Primary end-points 1. changes in the Kumamoto scale 2. cardiac impairment measured by echocardiographic assessment of global systolic strain ;Secondary Objective: Secondary end points 1. changes in nutritional status measured by the modified body mass index (mBMI) 2. changes in neurological impairment measured by the PND-score. 3. cardiac impairment measured by echocardiographic measurement of septal thickness and blood pro-BNP concentration. 4. Karnofsky performance scale 5. drug safety ;Primary end point(s): Primary endpoints will be: 1. changes in the Kumamoto scale 2. cardiac impairment measured by echocardiographic assessment of global systolic strain ;Timepoint(s) of evaluation of this end point: Primary and secondary end-points will be evaluated at 12 months and the end of the 24 months study period by descriptive statistical methods. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points will be: 1. changes in nutritional status measured by the modified body mass index (mBMI) 2. changes in neurological impairment measured by the PND-score. 3. cardiac impairment measured by echocardiographic measurement of septal thickness and blood pro-BNP concentration. 4. Karnofsky performance scale 5. drug safety ;Timepoint(s) of evaluation of this end point: Secondary endpoints for effect parameters will be evaluated at 12 months and the end of the 24 months study period by descriptive statistical methods. Safety parameters will be measured at 1 month (± 1 week), 3 months (±2 weeks), 6 months (± 1 month), 9 months (±1 month), 12 months (±1 month) and thereafter every 6 months (± 1month). | — |
Countries
Sweden
Contacts
Public ContactIntissar Anan
Umeå University Hospital
Outcome results
None listed