HyperthyroidismPhase 3NCT05118542
Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis
A Phase 3 study testing Propylthiouracil and Methimazole in people with Hyperthyroidism and Graves Disease, run by Universitas Indonesia at 1 site in Indonesia.
Trial summary
During July 2019 to August 2020, a single-blind clinical trial was done to 36 patients with Graves' disease. At the beginning of the study, subjects were accommodated into 2 groups, 17 into PTU groups and 19 into methimazole groups. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hyperthyroidism, Graves Disease, Atherosclerosis of Artery
- What is being tested?
- Propylthiouracil and Methimazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Jan 2019to 1 Aug 2020
- Phase
- Phase 3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged 18-65 years
- Newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month
- Agreed to participate in the study
Who cannot join
- Pregnancy
- History of coronary heart disease
- Known malignancy
- Current use of immunosuppressive medication sepsis, thyroid crisis
- Having allergic reaction to anti-thyroid drugs and other severe side effect
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
University of Indonesia
Jakarta Pusat, Jakarta Special Capital Region, 10430
About this study
Official title: Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis: Review on the Pathway of Insulin Resistance, Lipid, Inflammation, and Endothelial Dysfunction to Pulse Wave Velocity and Carotid Intima-Media Thickness
During July 2019 to August 2020, a single-blind clinical trial was done to 36 patients with Graves' disease. At the beginning of the study, subjects were accommodated into 2 groups, 17 into PTU groups and 19 into methimazole groups. There were 24 subjects who finished the study, 13 from PTU group and 11 from methimazole group. Blood serum was collected for HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin examination. Meanwhile stiffness and thickness of carotid artery was measured using PWV and cIMT.
Read the detailed description
This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect. Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Universitas Indonesia with approval number KET-784/UN.2.F1/ETIK/PPM.00.02/2019.
Study participant was observed every month for 3 months. Anti-thyroid drugs (PTU or methimazole) were given according to true simple randomization with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. At baseline visit, first and third month follow up, blood serum was collected to analyse HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin, meanwhile PWV and cIMT were measured using radiofrequency ultrasound examination of carotid arteries.
Categorical data was presented in frequency (%), while numerical data was presented using mean (SD) if normally distributed or median (IQR) if not normally distributed. Correlation Pearson test was performed for normal distributed data and Spearman test for not normal distributed data. To analyze the changes in parameter from baseline, first and third month, repeated ANOVA and General Linear Model test was performed. For not normally distributed data, transformation into normally distributed data was performed and the data was presented as geometric mean (CI 95%).
- Being tested
- Propylthiouracil, Methimazole
- Keywords
- Hyperthyroidism, Graves Disease, Atherosclerosis, Pathophysiology, Insulin Resistance, Lipid Marker, Inflammatory Marker, PWV, cIMT
- Medical subject headings
- Hyperthyroidism, Graves Disease, Atherosclerosis, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropylthiouracilDrug
PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.
MethimazoleDrug
methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.
| Study group | Role | What they receive |
|---|---|---|
| PTU Group | Active comparator | Propylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist Receives: Drug: Propylthiouracil |
| Methimazole Group | Active comparator | Methimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist Receives: Drug: Methimazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulse Wave Velocity
Pulse wave velocity was measured using radio frequency ultrasound in supine position at both left and right carotid artery
Measured: Change from Baseline to 3 month follow-up
carotid intima media thickness
cIMT was measured using radio frequency ultrasound in supine position at both left and right carotid artery
Measured: Change from Baseline to 3 month follow-up
Secondary outcomes (6)
HOMA-IR
HOMA-IR was calculated from patient fasting blood glucose and fasting insulin, which both were obtained through serum of the patient. Fasting blood glucose was measured using ECLIA methods with Abbott reagent, while fasting insulin were measured using ELISA with D\&G International Inc. kit
Measured: Change from Baseline to 3 month follow-up
LDL-R
LDL-R was measured from the patient serum using ELISA with D\&G International Inc. kit
Measured: Change from Baseline to 3 month follow-up
NFkB
NFkB was measured from the patient serum using ELISA with Cusabio kit
Measured: Change from Baseline to 3 month follow-up
sICAM-1
sICAM-1 was measured from the patient serum using ELISA with D\&G International Inc. kit
Measured: Change from Baseline to 3 month follow-up
sVCAM-1
sVCAM-1 was measured from the patient serum using ELISA with D\&G International Inc. kit
Measured: Change from Baseline to 3 month follow-up
sE-selectin
sE-selectin was measured from the patient serum using ELISA with D\&G International Inc. kit
Measured: Change from Baseline to 3 month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2021
- Study start1 Jan 2019
- Primary completion1 Jun 2020
- Study completion1 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HyperthyroidismStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect.
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wismandari, Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118542
- Sponsor's protocol ID
- 19-06-0752
- Status last verified
- Nov 2021
- First submitted
- 6 Oct 2021
- Last updated
- 12 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD would be share under specific request to the investigator
Publications
Bano A, Chaker L, Mattace-Raso FUS, van der Lugt A, Ikram MA, Franco OH, Peeters RP, Kavousi M. Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study. Circ Res. 2017 Dec 8;121(12):1392-1400. doi: 10.1161/CIRCRESAHA.117.311603. Epub 2017 Oct 31.
PubMed 29089349Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J. 2011;5:76-84. doi: 10.2174/1874192401105010076. Epub 2011 Feb 24.
PubMed 21660244Bilir C, Gokosmanoglu F, Caliskan M, Cinemre H, Akdemir R. Regression of the carotid intima media thickness by propylthiouracil therapy in Graves' hyperthyroidism. Am J Med Sci. 2012 Apr;343(4):273-6. doi: 10.1097/MAJ.0b013e31822a8284.
PubMed 21825964Inaba M, Henmi Y, Kumeda Y, Ueda M, Nagata M, Emoto M, Ishikawa T, Ishimura E, Nishizawa Y. Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients. Biomed Pharmacother. 2002 Jul;56(5):241-6. doi: 10.1016/s0753-3322(02)00195-6.
PubMed 12199623Upala S, Wirunsawanya K, Jaruvongvanich V, Sanguankeo A. Effects of statin therapy on arterial stiffness: A systematic review and meta-analysis of randomized controlled trial. Int J Cardiol. 2017 Jan 15;227:338-341. doi: 10.1016/j.ijcard.2016.11.073. Epub 2016 Nov 9.
PubMed 27839806Wisnu W, Alwi I, Nafrialdi N, Pemayun TGD, Pantoro NI, Wijaya CN, Tahapary DL, Tarigan TJE, Subekti I. The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial. J Lipid Atheroscler. 2024 Sep;13(3):358-370. doi: 10.12997/jla.2024.13.3.358. Epub 2024 Jun 12.
PubMed 39355401
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis: Review on the Pathway of Insulin Resistance, Lipid, Inflammation, and Endothelial Dysfunction to Pulse Wave Velocity and Carotid Intima-Media Thickness
- ClinicalTrials.gov ID
- NCT05118542
- Acronym / sponsor ID
- 19-06-0752
- Keywords
- Hyperthyroidism, Graves Disease, Atherosclerosis, Pathophysiology, Insulin Resistance, Lipid Marker, Inflammatory Marker, PWV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Aug 2020 (actual)
- First posted
- 12 Nov 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.
During July 2019 to August 2020, a single-blind clinical trial was done to 36 patients with Graves' disease. At the beginning of the study, subjects were accommodated into 2 groups, 17 into PTU groups and 19 into methimazole groups. There were 24 subjects who finished the study, 13 from PTU group and 11 from methimazole group. Blood serum was collected for HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin examination. Meanwhile stiffness and thickness of carotid artery was measured using PWV and cIMT.
Detailed description
This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect. Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Universitas Indonesia with approval number KET-784/UN.2.F1/ETIK/PPM.00.02/2019.
Study participant was observed every month for 3 months. Anti-thyroid drugs (PTU or methimazole) were given according to true simple randomization with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. At baseline visit, first and third month follow up, blood serum was collected to analyse HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin, meanwhile PWV and cIMT were measured using radiofrequency ultrasound examination of carotid arteries.
Categorical data was presented in frequency (%), while numerical data was presented using mean (SD) if normally distributed or median (IQR) if not normally distributed. Correlation Pearson test was performed for normal distributed data and Spearman test for not normal distributed data. To analyze the changes in parameter from baseline, first and third month, repeated ANOVA and General Linear Model test was performed. For not normally distributed data, transformation into normally distributed data was performed and the data was presented as geometric mean (CI 95%).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect.
| Arm | Type | Receives |
|---|---|---|
| PTU Group | Active comparator | Drug: PropylthiouracilPropylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist |
| Methimazole Group | Active comparator | Drug: MethimazoleMethimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult patients aged 18-65 years
- Newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month
- Agreed to participate in the study
Key exclusion criteria (5 listed)
- Pregnancy
- History of coronary heart disease
- Known malignancy
- Current use of immunosuppressive medication sepsis, thyroid crisis
- Having allergic reaction to anti-thyroid drugs and other severe side effect
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropylthiouracilPTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. | Drug | PTU Group |
| Methimazolemethimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. | Drug | Methimazole Group |
Primary outcome
Pulse Wave Velocity
Time frame: Change from Baseline to 3 month follow-up
Pulse wave velocity was measured using radio frequency ultrasound in supine position at both left and right carotid artery
carotid intima media thickness
Time frame: Change from Baseline to 3 month follow-up
cIMT was measured using radio frequency ultrasound in supine position at both left and right carotid artery
6 secondary outcomes
HOMA-IR
Time frame: Change from Baseline to 3 month follow-up
LDL-R
Time frame: Change from Baseline to 3 month follow-up
NFkB
Time frame: Change from Baseline to 3 month follow-up
sICAM-1
Time frame: Change from Baseline to 3 month follow-up
sVCAM-1
Time frame: Change from Baseline to 3 month follow-up
sE-selectin
Time frame: Change from Baseline to 3 month follow-up
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 12 Nov 2021.
- Background: PubMed 29089349Bano A, Chaker L, Mattace-Raso FUS, van der Lugt A, Ikram MA, Franco OH, Peeters RP, Kavousi M. Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study. Circ Res. 2017 Dec 8;121(12):1392-1400. doi: 10.1161/CIRCRESAHA.117.311603. Epub 2017 Oct 31.
- Background: PubMed 21660244Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J. 2011;5:76-84. doi: 10.2174/1874192401105010076. Epub 2011 Feb 24.
- Background: PubMed 21825964Bilir C, Gokosmanoglu F, Caliskan M, Cinemre H, Akdemir R. Regression of the carotid intima media thickness by propylthiouracil therapy in Graves' hyperthyroidism. Am J Med Sci. 2012 Apr;343(4):273-6. doi: 10.1097/MAJ.0b013e31822a8284.
- Background: PubMed 12199623Inaba M, Henmi Y, Kumeda Y, Ueda M, Nagata M, Emoto M, Ishikawa T, Ishimura E, Nishizawa Y. Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients. Biomed Pharmacother. 2002 Jul;56(5):241-6. doi: 10.1016/s0753-3322(02)00195-6.
- Background: PubMed 27839806Upala S, Wirunsawanya K, Jaruvongvanich V, Sanguankeo A. Effects of statin therapy on arterial stiffness: A systematic review and meta-analysis of randomized controlled trial. Int J Cardiol. 2017 Jan 15;227:338-341. doi: 10.1016/j.ijcard.2016.11.073. Epub 2016 Nov 9.
- Derived from this study: PubMed 39355401Wisnu W, Alwi I, Nafrialdi N, Pemayun TGD, Pantoro NI, Wijaya CN, Tahapary DL, Tarigan TJE, Subekti I. The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial. J Lipid Atheroscler. 2024 Sep;13(3):358-370. doi: 10.12997/jla.2024.13.3.358. Epub 2024 Jun 12.
- Individual participant dataSharing planned: No. IPD would be share under specific request to the investigator
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Propylthiouracil and Methimazole in people with Hyperthyroidism and Graves Disease, run by Universitas Indonesia at 1 site in Indonesia.
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 3 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: finished, as of the sponsor's last update on 12 Nov 2021. 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 Indonesia. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Pulse Wave Velocity (time frame: Change from Baseline to 3 month follow-up). The study lists 2 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 NCT05118542, which also lists 6 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 12 Nov 2021.