Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis

Graves Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05118542
• Other study ID #: 19-06-0752
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2019
• Est. completion date: August 1, 2020

Study information

• Verified date: November 2021
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerosis of Artery
• Graves Disease
• Hyperthyroidism
• Pathophysiology

Intervention

Drug:
• Propylthiouracil
PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.
• Methimazole
methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

Locations

Country	Name	City	State
Indonesia	University of Indonesia	Jakarta Pusat	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (5)

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. — View Citation

Bilir C, Gökosmanoglu 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. — View Citation

Inaba 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. — View Citation

Rizos 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. — View Citation

Upala 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulse Wave Velocity	Pulse wave velocity was measured using radio frequency ultrasound in supine position at both left and right carotid artery	Change from Baseline to 3 month follow-up
Primary	carotid intima media thickness	cIMT was measured using radio frequency ultrasound in supine position at both left and right carotid artery	Change from Baseline to 3 month follow-up
Secondary	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	Change from Baseline to 3 month follow-up
Secondary	LDL-R	LDL-R was measured from the patient serum using ELISA with D&G International Inc. kit	Change from Baseline to 3 month follow-up
Secondary	NFkB	NFkB was measured from the patient serum using ELISA with Cusabio kit	Change from Baseline to 3 month follow-up
Secondary	sICAM-1	sICAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit	Change from Baseline to 3 month follow-up
Secondary	sVCAM-1	sVCAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit	Change from Baseline to 3 month follow-up
Secondary	sE-selectin	sE-selectin was measured from the patient serum using ELISA with D&G International Inc. kit	Change from Baseline to 3 month follow-up