Papillary Thyroid CancerTEMPESTNCT05752669
Oxidative Stress and Mitochondrial TERT in Papillary Thyroid Cancer.
An observational study of Papillary Thyroid Cancer, run by Istituto Auxologico Italiano at 1 site in Italy.
Trial summary
Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Papillary Thyroid Cancer
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 15 Sep 2021to 31 May 2025
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients operated for papillary thyroid cancer and followed by our Center of Excellence for the Diagnosis and Treatment of Thyroid Tumors.
Who may be able to join
- Patients with papillary thyroid cancer
- Patients whose tumor and contralateral healthy tissues can be collected for the analyses
Who cannot join
- patients who did not provide consent
- patients lost at follow-up
- tissues not adequate for the analyses
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Oxidative Stress and Mitochondrial TERT in the Progression and Therapeutic Resistance of Papillary Thyroid Cancer.
Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. On the other hand, TERT contributes to mitochondrial OS protection, which could increase the resistance of cancer cells to therapeutic agents. The investigators aim to address the role of OS and mitochondrial TERT in the progression and therapeutic resistance of PTC. OS and TERT subcellular localization will be investigated in 150 PTCs and correlated to the genetic and expression profile of the tumors and to the clinical and prognostic features of the patients. Mechanisms implicated in TERT mitochondrial migration and the contribution of mitochondrial TERT to tumor progression will be investigated in cancer cell lines and primary cell cultures. This study will allow to identify OS as a marker of therapeutic resistance in PTC and will open new opportunities for the development of novel treatments targeting ROS generation/TERT nuclear export.
- Conditions
- Papillary Thyroid Cancer
- Medical subject headings
- Thyroid Cancer, Papillary
What is being measured
The primary outcome is the main question the study is designed to answer.
H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues.
Measured: months 1-24
TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.
TERT mitochondrial localization will be investigated by Western blot of mitochondrial fractions and normalized to VDAC protein expression.
Measured: months 13-30
Effect of exogenous oxidative stress (H2O2) and therapeutic agents (BRAF, MEK and Src kinase inhibitors) on TERT nuclear to mitochondrial translocation in thyroid cancer cell lines.
TERT mitochondrial translocation will be measured by immunofluorescence.
Measured: month 19-30
Mitochondrial oxidative stress generation in cells lines treated with Src kinase inhibitors.
Mitochondrial oxidative stress will be measured by immunofluorescence.
Measured: months 25-36
Proliferation in cells lines treated with Src kinase inhibitors.
Proliferation will be measured by a colorimetric assay.
Measured: months 25-36
Apoptosis in cells lines treated with Src kinase inhibitors.
Apoptosis will be measured by a luminometric assay.
Measured: months 25-36
Migration in cells lines treated with Src kinase inhibitors.
Migration will be measured by wound healing assays.
Measured: months 25-36
Secondary outcomes (2)
Genetic characterization of tumor tissues.
Point mutations and fusions will be investigated in DNA and RNA, respectively,
Measured: months 1-24
Expression profile of tumor tissues.
The expression level of 16 thyroid function genes will be investigated by a custom RNA sequencing panel.
Measured: months 1-24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2023
- Study start15 Sep 2021
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Papillary Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Istituto Auxologico ItalianoThe sponsor's other registered studies.
- 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
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Auxologico Italiano
- Sponsor type
- University, hospital or other
- Collaborators
- University of Milan
- Responsible party
- Sponsor
- Investigators
- Marina Muzza, PhD, Principal investigator, Istituto Auxologico Italiano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05752669
- Sponsor's protocol ID
- 05M902
- Acronym
- TEMPEST
- Status last verified
- Aug 2025
- First submitted
- 21 Feb 2023
- Last updated
- 21 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Muzza M, Colombo C, Cirello V, Perrino M, Vicentini L, Fugazzola L. Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer. Mol Cell Endocrinol. 2016 Aug 15;431:54-61. doi: 10.1016/j.mce.2016.05.005. Epub 2016 May 7.
PubMed 27164443Pesenti C, Muzza M, Colombo C, Proverbio MC, Fare C, Ferrero S, Miozzo M, Fugazzola L, Tabano S. MassARRAY-based simultaneous detection of hotspot somatic mutations and recurrent fusion genes in papillary thyroid carcinoma: the PTC-MA assay. Endocrine. 2018 Jul;61(1):36-41. doi: 10.1007/s12020-017-1483-2. Epub 2017 Dec 6.
PubMed 29214440Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014 Oct 23;159(3):676-90. doi: 10.1016/j.cell.2014.09.050.
PubMed 25417114Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.
PubMed 26462967Coperchini F, Croce L, Denegri M, Awwad O, Ngnitejeu ST, Muzza M, Capelli V, Latrofa F, Persani L, Chiovato L, Rotondi M. The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors. Sci Rep. 2019 Mar 13;9(1):4390. doi: 10.1038/s41598-019-40818-w.
PubMed 30867499
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Oxidative Stress and Mitochondrial TERT in the Progression and Therapeutic Resistance of Papillary Thyroid Cancer.
- ClinicalTrials.gov ID
- NCT05752669
- Acronym / sponsor ID
- TEMPEST / 05M902
- Conditions
- Papillary Thyroid Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Istituto Auxologico ItalianoUniversity, hospital or other
- Collaborators
- University of Milan
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 3 Mar 2023 (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.
Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. On the other hand, TERT contributes to mitochondrial OS protection, which could increase the resistance of cancer cells to therapeutic agents. The investigators aim to address the role of OS and mitochondrial TERT in the progression and therapeutic resistance of PTC. OS and TERT subcellular localization will be investigated in 150 PTCs and correlated to the genetic and expression profile of the tumors and to the clinical and prognostic features of the patients. Mechanisms implicated in TERT mitochondrial migration and the contribution of mitochondrial TERT to tumor progression will be investigated in cancer cell lines and primary cell cultures. This study will allow to identify OS as a marker of therapeutic resistance in PTC and will open new opportunities for the development of novel treatments targeting ROS generation/TERT nuclear export.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients operated for papillary thyroid cancer and followed by our Center of Excellence for the Diagnosis and Treatment of Thyroid Tumors.
Key inclusion criteria (2 listed)
- Patients with papillary thyroid cancer
- Patients whose tumor and contralateral healthy tissues can be collected for the analyses
Key exclusion criteria (3 listed)
- patients who did not provide consent
- patients lost at follow-up
- tissues not adequate for the analyses
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
H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues.
Time frame: months 1-24
TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.
Time frame: months 13-30
TERT mitochondrial localization will be investigated by Western blot of mitochondrial fractions and normalized to VDAC protein expression.
Effect of exogenous oxidative stress (H2O2) and therapeutic agents (BRAF, MEK and Src kinase inhibitors) on TERT nuclear to mitochondrial translocation in thyroid cancer cell lines.
Time frame: month 19-30
TERT mitochondrial translocation will be measured by immunofluorescence.
Mitochondrial oxidative stress generation in cells lines treated with Src kinase inhibitors.
Time frame: months 25-36
Mitochondrial oxidative stress will be measured by immunofluorescence.
Proliferation in cells lines treated with Src kinase inhibitors.
Time frame: months 25-36
Proliferation will be measured by a colorimetric assay.
Apoptosis in cells lines treated with Src kinase inhibitors.
Time frame: months 25-36
Apoptosis will be measured by a luminometric assay.
Migration in cells lines treated with Src kinase inhibitors.
Time frame: months 25-36
Migration will be measured by wound healing assays.
2 secondary outcomes
Genetic characterization of tumor tissues.
Time frame: months 1-24
Expression profile of tumor tissues.
Time frame: months 1-24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
- Background: PubMed 27164443Muzza M, Colombo C, Cirello V, Perrino M, Vicentini L, Fugazzola L. Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer. Mol Cell Endocrinol. 2016 Aug 15;431:54-61. doi: 10.1016/j.mce.2016.05.005. Epub 2016 May 7.
- Background: PubMed 29214440Pesenti C, Muzza M, Colombo C, Proverbio MC, Fare C, Ferrero S, Miozzo M, Fugazzola L, Tabano S. MassARRAY-based simultaneous detection of hotspot somatic mutations and recurrent fusion genes in papillary thyroid carcinoma: the PTC-MA assay. Endocrine. 2018 Jul;61(1):36-41. doi: 10.1007/s12020-017-1483-2. Epub 2017 Dec 6.
- Background: PubMed 25417114Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014 Oct 23;159(3):676-90. doi: 10.1016/j.cell.2014.09.050.
- Background: PubMed 26462967Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.
- Background: PubMed 30867499Coperchini F, Croce L, Denegri M, Awwad O, Ngnitejeu ST, Muzza M, Capelli V, Latrofa F, Persani L, Chiovato L, Rotondi M. The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors. Sci Rep. 2019 Mar 13;9(1):4390. doi: 10.1038/s41598-019-40818-w.
- PubMed ID: 27164443Link provided by the sponsor.
- PubMed ID: 29214440Link provided by the sponsor.
- PubMed ID: 25417114Link provided by the sponsor.
- PubMed ID: 26462967Link provided by the sponsor.
- PubMed ID: 30867499Link provided by the sponsor.
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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.
Marina Muzza, PhD principal investigator
Istituto Auxologico Italiano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Papillary Thyroid Cancer, run by Istituto Auxologico Italiano at 1 site in Italy.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues. (time frame: months 1-24). The study lists 7 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 NCT05752669, which also lists 5 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 21 Aug 2025.