Amyloid Proteins From Medullary Thyroid Cancer and Laryngeal Amyloidosis

Sponsor

The Leeds Teaching Hospitals NHS Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04760171

Collaborator

University of Leeds (Other)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Using excess tumour samples that contain amyoid, from patients with Medullary Thyroid Cancer, we aim to determine the structures of ex vivo amyloid fibrils from human tumour tissue samples and compare them with that of existing stock of in vitro formed amyloid fibrils. This will permit the analysis of the effects of gene mutation and post-translational modification on the development of amyloid from a disease state.

Amyloid is known to accumulate in the brain tissue of patients with neuro-degenerative conditions such as Alzheimer's disease and Dementia. Therefore solving the structure of amyloid fibrils may aid the development of future treatments for these conditions.

Condition or Disease	Intervention/Treatment	Phase
Amyloid Medullary Thyroid Cancer Alzheimer Disease Dementia

Detailed Description

This is an anonymous, voluntary inclusion, laboratory based, basic science research study. Appropriate patients who meet the inclusion criteria and complete the consent process will be asked to donate a small sample of excess tumour tissue after the completion of their surgical procedure. This tissue will be transferred to the research laboratory in Leeds University for analysis and subject to a variety of investigations and scientific procedures to achieve the study objectives.

These include:

- amyloid extraction by tissue homogenization and centrifugation as already documented in the literature.
- mass spectrometry analysis to identify and characterize the most prominent proteins present in the amyloid deposits and their possible post-translational modifications.
- Transmission Electron Microscopy to characterize at the gross features of the extracted amyloid fibrils at low resolution (>20Å). This relatively simple procedure allows for quick characterization of the samples in order to optimize them for Atomic Force Microscopy (AFM) and Cryo-Electron Microscopy (Cryo-EM).
- Atomic Force microscopy to characterize helical parameters of the amyloid fibrils needed to calculate the structure from Cryo-EM data.
- Cryo-Electron Microscopy to elucidate the structure of the amyloids extracted from tissue affected in each disease

Study Design

Study Type:

Observational

Anticipated Enrollment :

10 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

An ex Vivo Study to Purify Amyloid Fibrils and Solve Their 3D Structures Using Amyloid Proteins From Medullary Thyroid Cancer and Laryngeal Amyloidosis

Anticipated Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Patients diagnosed with medullary thyroid cancer (MTC) who are undergoing standard surgical treatment for their disease. This will be either hemithyroidectomy or total thyroidectomy. Patients with laryngeal amyloidosis (LA) who are undergoing standard surgical treatment of this disease. This will be microlaryngoscopy & biopsy/debulking

Outcome Measures

Primary Outcome Measures

Amyloid extraction by tissue homogenization and centrifugation [12-24 months]
A standard laboratory technique for subsequent analysis
Transmission electron microscopy [12-24 months]
To characterize the gross features of the extracted amyloid fibrils at low resolution (>20Å). This relatively simple procedure allows for quick characterization of the samples in order to optimize them for Atomic Force Microscopy (AFM) and Cryo-Electron Microscopy (Cryo-EM).
Atomic force microscopy [12-24 months]
To characterize helical parameters of the amyloid fibrils needed to calculate the structure from Cryo-EM data.
Cryo-electron microscopy (Cryo-EM) [12-24 months]
To elucidate the structure of the amyloids extracted from tissue affected in each disease
Mass spectrometry [12-24 months]
Analysis to identify and characterize the most prominent proteins present in the amyloid deposits and their possible post-translational modifications.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Inclusion Criteria:

Diagnosed with known or suspected MTC or LA
Age >= 18 years, no upper age limit
Able to provide informed consent for both surgical treatment and inclusion into this study
For MTC patients, treatment recommendation from the Thyroid MDT is for either hemithyroidectomy or total thyroidectomy
for LA patients, agreement with their attending clinician to undergo surgical debulking of disease under general anaesthetic. The procedure is called 'microlaryngoscopy and biopsy/debulking'

Exclusion Criteria:

No known or suspected diagnosis of MTC or LA
Age <18 years
Unable to provide informed consent
Treatment recommendation from Thyroid MDT is for any treatment excluding primary surgery (ie palliation, best supportive care, chemotherapy, radiotherapy etc)
For LA patients, no agreement between patient and attending clinician to proceed with surgery as primary treatment.