Clinical trial NCT01432587: The Effect of Diflunisal on Familial Transthyretin Amyloidosis
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Amyloidosis
Keywords: Amyloidosis
Transthyretin
Neuropathies
Diflunisal
Familial
Lead sponsor: Umeå University
Sponsor class: OTHER
First posted: 2011-09-13
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients visiting the Units for Familal amyloidosis in Umeå, Piteå and Skellefteå

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.

Eligibility 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.

Primary outcomes:
measure: Changes in the Kumamoto scale
timeFrame: Enrollment, 12 month and annual follow-up
Secondary outcomes:
measure: Changes in modified body mass index (mBMI)
timeFrame: Enrollment, 12 month and annual follow-up
measure: Changes in paraneoplastic neurological disorders (PND) scale
timeFrame: Enrollment, 12 month and annual follow-up
measure: Changes in cardiac function
timeFrame: Enrollment, 1 month, 2 month, 3 month, 6 month, 9 month 12 month, 18 month and annual follow-up
measure: Safety follow-up Blood Work
timeFrame: 1 month, 3 month, 6 month, 9 month, 12 month and follow-up every 6 months
Other outcomes:
Locations:
city: Piteå
country: Sweden
facility: Dept of Clinical Medicin, Ptieå Hospital
city: Skellefteå
country: Sweden
facility: Dept of clinical medicin, Skellefteå Hospital
city: Umeå
country: Sweden
facility: Dept of Clinical Medicine, Umeå University Hospital
Study officials:
affiliation: Dept of Clinical Medicine and public Health, Umeå University
name: Ole B Suhr, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: