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Trial record 1 of 1 for:    "Hereditary Transthyretin Amyloidosis" | "Diflunisal"
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Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis (MED-hATTR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03431896
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : March 1, 2019
Information provided by (Responsible Party):
Mazen Hanna MD, The Cleveland Clinic

Tracking Information
First Submitted Date February 7, 2018
First Posted Date February 13, 2018
Last Update Posted Date March 1, 2019
Actual Study Start Date February 1, 2018
Estimated Primary Completion Date February 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 7, 2018)
Average % change in oligomers in patients with new onset TTR amyloid symptoms [ Time Frame: Annually over 5 years ]
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03431896 on Archive Site
Current Secondary Outcome Measures
 (submitted: February 7, 2018)
% change of oligomer levels relative to baseline level in patients with ATTR specific medication changes [ Time Frame: Annually over 5 years ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis
Official Title Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis
Brief Summary This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.
Detailed Description Recent advances in genetic testing have allowed for pathogenic mutation identification in family members of affected individuals prior to onset of symptoms. While the presence of mutation and the corresponding TTR kinetic stability have been directly linked to disease development, the molecular drivers of tissue specific degeneration have not been defined. We hypothesize that soluble misfolded TTR oligomer species may be circulating within the blood of these patients possibly years prior to amyloid deposition and could serve as an early biomarker and/or driver for disease development. In this line, The Scripps Research Institute has developed a peptide-based probe that specifically labels and integrates into misfolded TTR oligomers allowing the relative circulating concentration in the bloodstream to be determined. Longitudinal monitoring of untreated, asymptomatic TTR amyloid genetic carriers utilizing the Scripps probe is likely to provide novel insight into early disease progression. We also plan to utilize the Scripps probe to monitor disease progression in TTR amyloid genetic carriers currently undergoing treatment by observing how treatments affect the circulating misfolded TTR oligomers. Through enhanced understanding of early disease progression and treatment efficacy, our hope is to limit amyloid accumulation in cardiac and nerve tissue and delay the development of the invariably fatal TTR amyloid cardiomyopathy/neuropathy.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Whole Blood
Sampling Method Non-Probability Sample
Study Population Participants will be identified through clinical practice and from Amyloid support groups
  • Amyloidosis
  • Amyloid
  • Amyloid Neuropathies, Familial
  • Amyloid Cardiomyopathy
  • Amyloid - Primary
  • Transthyretin Amyloidosis
  • AL Amyloidosis
Intervention Not Provided
Study Groups/Cohorts Primary

1.) To evaluate the relative amount of misfolded ATTR oligomers in asymptomatic ATTR amyloid genetic carriers and correlate their levels with clinical symptoms and outcomes.

  1. Determine if misfolded ATTR oligomers are elevated compared to healthy control data obtained by Scripps during probe development
  2. Describe the levels longitudinally
  3. Determine if treatment with ATTR-specific medications (examples: diflunisal, doxycycline, ursodiol, tauroursodeoxycholic acid (TUDCA), green tea extract, curcumin, tafamidis, inotersen, patisiran) lead to reduction in the probe levels in those with elevated levels at baseline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 28, 2019)
Original Estimated Enrollment
 (submitted: February 7, 2018)
Estimated Study Completion Date February 15, 2024
Estimated Primary Completion Date February 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients with known hereditary ATTR amyloidosis genetic mutations as identified by genetic testing.

Exclusion Criteria:

  • Patients with ATTR amyloidosis identified as wild-type.
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contact: Mazen A Hanna, MD 216-444-3490
Contact: Joseph P Donnelly, MD 216-444-3490
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT03431896
Other Study ID Numbers 17-1301
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Mazen Hanna MD, The Cleveland Clinic
Study Sponsor The Cleveland Clinic
Collaborators Not Provided
Principal Investigator: Mazen A Hanna, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date February 2019