AmyloidNCT04760171
Amyloid Proteins From Medullary Thyroid Cancer and Laryngeal Amyloidosis
An observational study of Amyloid and Medullary Thyroid Cancer, run by The Leeds Teaching Hospitals NHS Trust.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloid, Medullary Thyroid Cancer, Alzheimer Disease
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Feb 2021to Feb 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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
Who may be able to join
- 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'
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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
- Conditions
- Amyloid, Medullary Thyroid Cancer, Alzheimer Disease, Dementia
- Medical subject headings
- Alzheimer Disease, Carcinoma, Medullary, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Amyloid extraction by tissue homogenization and centrifugation
A standard laboratory technique for subsequent analysis
Measured: 12-24 months
Transmission electron microscopy
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).
Measured: 12-24 months
Atomic force microscopy
To characterize helical parameters of the amyloid fibrils needed to calculate the structure from Cryo-EM data.
Measured: 12-24 months
Cryo-electron microscopy (Cryo-EM)
To elucidate the structure of the amyloids extracted from tissue affected in each disease
Measured: 12-24 months
Mass spectrometry
Analysis to identify and characterize the most prominent proteins present in the amyloid deposits and their possible post-translational modifications.
Measured: 12-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study startFeb 2021 (estimated)
- Primary completionFeb 2023 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AmyloidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Leeds Teaching Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Leeds
- Responsible party
- Sponsor
- Investigators
- James Moor, FRCS, Principal investigator, Leeds Teaching Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760171
- Sponsor's protocol ID
- EN21/138414
- Status last verified
- Feb 2021
- First submitted
- 10 Feb 2021
- Last updated
- 18 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Samples will be anonymised, and research outputs will be based on the whole cohort. Therefore IPD will not be available.
Publications
GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):459-480. doi: 10.1016/S1474-4422(18)30499-X. Epub 2019 Mar 14.
PubMed 30879893Knowles TP, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol. 2014 Jun;15(6):384-96. doi: 10.1038/nrm3810.
PubMed 24854788Gallardo R, Iadanza MG, Xu Y, Heath GR, Foster R, Radford SE, Ranson NA. Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly. Nat Struct Mol Biol. 2020 Nov;27(11):1048-1056. doi: 10.1038/s41594-020-0496-3. Epub 2020 Sep 14.
PubMed 32929282Gallardo R, Ranson NA, Radford SE. Amyloid structures: much more than just a cross-beta fold. Curr Opin Struct Biol. 2020 Feb;60:7-16. doi: 10.1016/j.sbi.2019.09.001. Epub 2019 Nov 1.
PubMed 31683043
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04760171
- Acronym / sponsor ID
- EN21/138414
- Conditions
- Amyloid, Medullary Thyroid Cancer, Alzheimer Disease, Dementia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- The Leeds Teaching Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- University of Leeds
- Study start
- Feb 2021 (estimated)
- Primary completion
- Feb 2023 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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'
Key exclusion criteria (5 listed)
- No known or suspected diagnosis of MTC or LA
- Age <18 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Amyloid extraction by tissue homogenization and centrifugation
Time frame: 12-24 months
A standard laboratory technique for subsequent analysis
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).
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.
Cryo-electron microscopy (Cryo-EM)
Time frame: 12-24 months
To elucidate the structure of the amyloids extracted from tissue affected in each disease
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Background: PubMed 30879893GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):459-480. doi: 10.1016/S1474-4422(18)30499-X. Epub 2019 Mar 14.
- Background: PubMed 24854788Knowles TP, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol. 2014 Jun;15(6):384-96. doi: 10.1038/nrm3810.
- Background: PubMed 32929282Gallardo R, Iadanza MG, Xu Y, Heath GR, Foster R, Radford SE, Ranson NA. Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly. Nat Struct Mol Biol. 2020 Nov;27(11):1048-1056. doi: 10.1038/s41594-020-0496-3. Epub 2020 Sep 14.
- Background: PubMed 31683043Gallardo R, Ranson NA, Radford SE. Amyloid structures: much more than just a cross-beta fold. Curr Opin Struct Biol. 2020 Feb;60:7-16. doi: 10.1016/j.sbi.2019.09.001. Epub 2019 Nov 1.
- Individual participant dataSharing planned: No. Samples will be anonymised, and research outputs will be based on the whole cohort. Therefore IPD will not be available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Moor, FRCS principal investigator
Leeds Teaching Hospitals NHS Trust
Questions about this trial
What is this clinical trial studying?
An observational study of Amyloid and Medullary Thyroid Cancer, run by The Leeds Teaching Hospitals NHS Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anne Gowing (+441132060469, anne.gowing@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amyloid extraction by tissue homogenization and centrifugation (time frame: 12-24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04760171, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.