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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

Brief Summary:
This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.

Condition or disease
Amyloidosis Amyloid Amyloid Neuropathies, Familial Amyloid Cardiomyopathy Amyloid - Primary Transthyretin Amyloidosis AL Amyloidosis

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.

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : February 15, 2024
Estimated Study Completion Date : February 15, 2024


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

Primary Outcome Measures :
  1. Average % change in oligomers in patients with new onset TTR amyloid symptoms [ Time Frame: Annually over 5 years ]

Secondary Outcome Measures :
  1. % change of oligomer levels relative to baseline level in patients with ATTR specific medication changes [ Time Frame: Annually over 5 years ]

Biospecimen Retention:   Samples Without DNA
Whole Blood

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants will be identified through clinical practice and from Amyloid support groups

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03431896

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Contact: Mazen A Hanna, MD 216-444-3490
Contact: Joseph P Donnelly, MD 216-444-3490

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United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
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Principal Investigator: Mazen A Hanna, MD The Cleveland Clinic

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Responsible Party: Mazen Hanna MD, Co-Director, Amyloidosis Program, The Cleveland Clinic Identifier: NCT03431896     History of Changes
Other Study ID Numbers: 17-1301
First Posted: February 13, 2018    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Immunoglobulin Light-chain Amyloidosis
Amyloid Neuropathies, Familial
Amyloid Neuropathies
Disease Progression
Disease Attributes
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors