The Effect of Diflunisal on Familial Transthyretin Amyloidosis (DFNS01)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Umeå University
Sponsor:
Information provided by (Responsible Party):
Ole B Suhr, Professor, MD, PhD, Umeå University
ClinicalTrials.gov Identifier:
NCT01432587
First received: September 9, 2011
Last updated: June 26, 2013
Last verified: June 2013
  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:


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


Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Diflunisal
    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
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

Contacts
Contact: Ole B Suhr, Professor MD PhD +46 90 785 0000 ext 3959 ole.suhr@medicin.umu.se

Locations
Sweden
Dept of Clinical Medicin, Ptieå Hospital Recruiting
Piteå, Sweden, SE-941 28
Contact: Katarzyna Liszewska, MD    0911 - 750 00 ext 232    Katarzyna.Liszewska@nll.se   
Principal Investigator: Katarzyna Liszewska, MD         
Dept of clinical medicin, Skellefteå Hospital Recruiting
Skellefteå, Sweden, SE-931 86
Contact: Lars Wikström, MD    +46 910-7710 00 ext 1667    lars.wikstrom@vll.se   
Principal Investigator: Lars Wikström, MD         
Dept of Clinical Medicine, Umeå University Hospital Recruiting
Umeå, Sweden, SE-90185
Contact: Ole B Suhr, MD PhD    +46 90 785 0000 ext 3959    ole.suhr@medicin.umu.se   
Contact: Christina Frykholm, Nurse    +46 90 785 0000 ext 3959    fapteam.medicin@vll.se   
Principal Investigator: Ole B Suhr, MD PhD         
Sponsors and Collaborators
Umeå University
Investigators
Principal Investigator: Ole B Suhr, MD PhD Dept of Clinical Medicine and public Health, Umeå University
  More Information

No publications provided

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: June 26, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by Umeå University:
Amyloidosis
Transthyretin
Neuropathies
Diflunisal
Familial

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Diflunisal
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014