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

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT05118542

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperthyroidism Graves Disease Atherosclerosis of Artery Pathophysiology	Drug: Propylthiouracil Drug: Methimazole	Phase 3

Detailed Description

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

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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 (Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The care providers gave two choice of drug doses to the research assistant. The research assistant then give the participant their drugs based on the assignment from the randomisation. The investigator and outcome assessor were blinded to the drugs which the participants received

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2019

Actual Primary Completion Date :

Jun 1, 2020

Actual Study Completion Date :

Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PTU Group Propylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist	Drug: Propylthiouracil PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.
Active Comparator: Methimazole Group Methimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist	Drug: Methimazole methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

Arm

Intervention/Treatment

Active Comparator: PTU Group

Propylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist

Drug: Propylthiouracil

PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

Active Comparator: Methimazole Group

Methimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist

Drug: Methimazole

methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

Outcome Measures

Primary Outcome Measures

Pulse Wave Velocity [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 [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

Secondary Outcome Measures

HOMA-IR [Change from Baseline to 3 month follow-up]
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
LDL-R [Change from Baseline to 3 month follow-up]
LDL-R was measured from the patient serum using ELISA with D&G International Inc. kit
NFkB [Change from Baseline to 3 month follow-up]
NFkB was measured from the patient serum using ELISA with Cusabio kit
sICAM-1 [Change from Baseline to 3 month follow-up]
sICAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit
sVCAM-1 [Change from Baseline to 3 month follow-up]
sVCAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit
sE-selectin [Change from Baseline to 3 month follow-up]
sE-selectin was measured from the patient serum using ELISA with D&G International Inc. kit

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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