Clinical trial NCT05118542: Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperthyroidism
Graves Disease
Atherosclerosis of Artery
Pathophysiology
Keywords: Hyperthyroidism
Graves Disease
Atherosclerosis
Pathophysiology
Insulin Resistance
Lipid Marker
Inflammatory Marker
PWV
cIMT
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2021-11-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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%).

Eligibility criteria: 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

Primary outcomes:
measure: Pulse Wave Velocity
timeFrame: Change from Baseline to 3 month follow-up
measure: carotid intima media thickness
timeFrame: Change from Baseline to 3 month follow-up
Secondary outcomes:
measure: HOMA-IR
timeFrame: Change from Baseline to 3 month follow-up
measure: LDL-R
timeFrame: Change from Baseline to 3 month follow-up
measure: NFkB
timeFrame: Change from Baseline to 3 month follow-up
measure: sICAM-1
timeFrame: Change from Baseline to 3 month follow-up
measure: sVCAM-1
timeFrame: Change from Baseline to 3 month follow-up
measure: sE-selectin
timeFrame: Change from Baseline to 3 month follow-up
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: University of Indonesia
state: Jakarta
Study officials:
References:
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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. doi: 10.1016/s0753-3322(02)00195-6.
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.