Amyloid Proteins From Medullary Thyroid Cancer and Laryngeal Amyloidosis

February 15, 2021 updated by: The Leeds Teaching Hospitals NHS Trust

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

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.

Study Overview

Status

Not yet recruiting

Conditions

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:

  1. - amyloid extraction by tissue homogenization and centrifugation as already documented in the literature.
  2. - mass spectrometry analysis to identify and characterize the most prominent proteins present in the amyloid deposits and their possible post-translational modifications.
  3. - 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).
  4. - Atomic Force microscopy to characterize helical parameters of the amyloid fibrils needed to calculate the structure from Cryo-EM data.
  5. - Cryo-Electron Microscopy to elucidate the structure of the amyloids extracted from tissue affected in each disease

Study Type

Observational

Enrollment (Anticipated)

10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with MTC, who have been recommended via the Thyroid Multi-Disciplinary team meeting, to undergo hemi or total thyroidectomy surgery.

Patients with LA, who agree with their surgeon, to undergo surgical treatment of that condition

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amyloid extraction by tissue homogenization and centrifugation
Time Frame: 12-24 months
A standard laboratory technique for subsequent analysis
12-24 months
Transmission electron microscopy
Time Frame: 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).
12-24 months
Atomic force microscopy
Time Frame: 12-24 months
To characterize helical parameters of the amyloid fibrils needed to calculate the structure from Cryo-EM data.
12-24 months
Cryo-electron microscopy (Cryo-EM)
Time Frame: 12-24 months
To elucidate the structure of the amyloids extracted from tissue affected in each disease
12-24 months
Mass spectrometry
Time Frame: 12-24 months
Analysis to identify and characterize the most prominent proteins present in the amyloid deposits and their possible post-translational modifications.
12-24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Leeds Teaching Hospitals NHS Trust

Collaborators

University of Leeds

Investigators

  • Principal Investigator: James Moor, FRCS, Leeds Teaching Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2021

Primary Completion (Anticipated)

February 1, 2023

Study Completion (Anticipated)

February 1, 2026

Study Registration Dates

First Submitted

February 10, 2021

First Submitted That Met QC Criteria

February 15, 2021

First Posted (Actual)

February 18, 2021

Study Record Updates

Last Update Posted (Actual)

February 18, 2021

Last Update Submitted That Met QC Criteria

February 15, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EN21/138414

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Samples will be anonymised, and research outputs will be based on the whole cohort. Therefore IPD will not be available.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dementia

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Papua New Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe