Study of Cerebral MRI Anomalies in Mutated Transthyretin Amyloidosis Patients

Transthyretin Amyloidosis Clinical Trial

— TTR-SNC  

Official title:

A Comprehensive Retrospective Study of Cerebral MRI Anomalies in Mutated Transthyretin Amyloidosis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05075798
• Other study ID #: LOCAL/2021/II-01
• Secondary ID: IRB21.09.02
• Status: Completed
• Start date: October 25, 2021
• Est. completion date: May 31, 2022

Study information

• Verified date: September 2022
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Transthyretin amyloidosis (aTTR) initially described as a rare disease, became the most serious hereditary polyneuropathy of adult onset and family screening has made it possible to identify and follow up many asymptomatic patients and carriers of the mutation in the TTR gene.

Considered as a systemic disease with involvement of target organs (the heart, the eye, the kidney and peripheral nervous system), it seems to be more complex for neurologists according to recent publications raising the issue of central nervous system involvement.

Indeed, TTR amyloid deposits seem to be correlated with the duration of the disease. These deposits can cause cortical damage by different mechanisms: direct TTR toxicity or as a result of pathology related to cerebral amyloid angiopathy (intraparenchymal or subarachnoid hematomas, small infarcts, hemosiderin). A small number of mutations in the TTR gene cause a rare phenotype of systemic amyloidosis, the oculoleptomeningeal form, characterized by clinical neurological symptoms: progressive dementia, epilepsy, ataxia, spastic paraparesis, stroke-like episodes.

Hypothesis of the work: the central nervous system involvement is probably underestimated on the radiological description in patients with TTR mutation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 31, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients followed at the University Hospital of Nîmes between 2017 and 2021 for a TTR neuropathy with proven mutation, having benefited from a brain MRI.

Exclusion Criteria:

• Patients without TTR neuropathy with proven mutation, or who did not have a brain MRI.

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Transthyretin Amyloidosis

Intervention

Other:
• No intervention,
pure observational study

Locations

Country	Name	City	State
France	CHU de Nîmes	Nîmes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

References & Publications (5)

Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):124-37. doi: 10.1136/jnnp-2011-301308. Epub 2011 Nov 5. Review. — View Citation

Ikeda SI. [Cerebral amyloid angiopathy with familial transthyretin-derived oculoleptomeningeal amyloidosis]. Brain Nerve. 2013 Jul;65(7):831-42. Review. Japanese. — View Citation

Maia LF, Magalhães R, Freitas J, Taipa R, Pires MM, Osório H, Dias D, Pessegueiro H, Correia M, Coelho T. CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings. J Neurol Neurosurg Psychiatry. 2015 Feb;86(2 — View Citation

Nakagawa K, Sheikh SI, Snuderl M, Frosch MP, Greenberg SM. A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis. J Neurol Sci. 2008 Sep 15;272(1-2):186-90. doi: 10.1016/j.jns.2008.05.014. Epub 2008 Jun 24. — View Citation

Vieira M, Saraiva MJ. Transthyretin: a multifaceted protein. Biomol Concepts. 2014 Mar;5(1):45-54. doi: 10.1515/bmc-2013-0038. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical-radiological characterization	Presence of signs of chronic bleeding on brain MRI (Yes/No)	Baseline