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

NCT05118542 | Completed Phase 3 DMC

• 1 other identifier: 19-06-0752
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperthyroidism; Graves Disease; Atherosclerosis of Artery; Pathophysiology

Keywords

Hyperthyroidism; Graves Disease; Atherosclerosis; Pathophysiology; Insulin Resistance; Lipid Marker; Inflammatory Marker; PWV; cIMT

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• HOMA-IR

  Change from Baseline to 3 month follow-up

• LDL-R

  Change from Baseline to 3 month follow-up

• NFkB

  Change from Baseline to 3 month follow-up

• sICAM-1

  Change from Baseline to 3 month follow-up

• sVCAM-1

  Change from Baseline to 3 month follow-up

Study Arms (2)

PTU Group

ACTIVE COMPARATOR

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

Drug: Propylthiouracil

Methimazole Group

ACTIVE COMPARATOR

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

Drug: Methimazole

Interventions

Propylthiouracil DRUG

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

PTU Group

Methimazole DRUG

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

Methimazole Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

University of Indonesia

Jakarta Pusat, Jakarta Special Capital Region, 10430, Indonesia

Location

Related Publications (6)

• 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.

  PMID: 29089349 BACKGROUND

• 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.

  PMID: 21660244 BACKGROUND

• Bilir 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.

  PMID: 21825964 BACKGROUND

• 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.

  PMID: 12199623 BACKGROUND

• 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.

  PMID: 27839806 BACKGROUND

• Wisnu 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.

  PMID: 39355401 DERIVED

MeSH Terms

Conditions

Hyperthyroidism; Graves Disease; Atherosclerosis; Insulin Resistance

Interventions

Propylthiouracil; Methimazole

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases; Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Autoimmune Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Imidazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: November 12, 2021
• Study Start: January 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: August 1, 2020
• Last Updated: November 12, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)