Effects of Different Treatment Schemes on the Regulation and Recurrence of Graves' Disease

NCT05461820 | Recruiting Phase 4 DMC

• 1 other identifier: 2016-SR-037
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the dose of methimazole was adjusted according to the different states of thyroid function, and the effects of conventional therapy and intensive therapy on the cumulative recurrence of Graves' hyperthyroidism after two years of drug withdrawal were evaluated. At the same time, the changes of immune indexes and inflammatory factors in the regulation process were evaluated. This study is a phase IV clinical study designed and carried out by the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), which is a randomized, open and routine treatment group with parallel control.

Conditions

Graves Disease; Relapse; Treatment; Drug Withdrawal

Outcome Measures

Primary Outcomes (2)

• Cumulative recurrence rate between conventional treatment group and intensive treatment group after two years of withdrawal.

  Patients took medicine according to the course of treatment. Relapse occurs when the thyroid function returns to hyperthyroidism within 2 years after the drug is stopped.

  Up to 2 years after drug withdrawal

• Number of patients with no adverse reactions during the treatment of Graves' disease

  The patient completed the methimazole treatment, and there were no adverse reactions that needed to be stopped. Adverse reactions refer to any symptoms, syndromes or diseases that affect patients' health during clinical research and observation, and also include clinically relevant situations found in the laboratory or other diagnostic processes, such as unplanned diagnosis and treatment measures, withdrawal from research, or clinically significant laboratory examination items. Blood routine, liver function, kidney function and adverse reactions will be recorded during the follow-up.

  Within the treatment period (average 2 years)

Secondary Outcomes (4)

• Cumulative recurrence rate of hyperthyroidism in conventional treatment group and intensive treatment group after stopping treatment for one year.

  Up to 1 years after drug withdrawal

• Effects of routine treatment and intensive treatment on titer and positive rate of thyroid autoantibodies

  During treatment(average 2 years) and within 2 years after drug withdrawal

• Effect of conventional therapy and intensive therapy on thyroid volume

  During treatment(average 2 years) and within 2 years after drug withdrawal

• Effects of conventional therapy and intensive therapy on cytokines

  During treatment(average 2 years) and within 2 years after drug withdrawal

Study Arms (2)

Conventional treatment group

ACTIVE COMPARATOR

According to the thyroid function, if the initial free thyroxine(FT4) ≥ 3 times the normal value, the initial dose of methimazole is 30mg/ day, the thyroid function will be tested every four weeks, and the dose will be reduced when thyroid stimulating hormone(TSH) \> normal lower limit or free triiodothyronine(FT3) \< normal lower limit or FT4 \< normal lower limit. The dose will be reduced according to the clinical routine, specifically, every day (30 mg→20 mg→10 mg→5mg→2.5 mg) If the initial FT4 is less than 3 times the normal value, the initial dose of methimazole is 15mg/ day, and the thyroid function is tested every four weeks. When TSH is greater than the normal lower limit or FT3 is less than the normal lower limit or FT4 is less than the normal lower limit, the dose will be reduced according to the clinical routine, specifically every day for 24 months. If TSH \> 100 mIU/L occurs during the treatment, the reduction speed will be accelerated, and 1-2 dose levels can be skipped.

Drug: Methimazole

Intensive treatment group

ACTIVE COMPARATOR

If the initial FT4≥ 3 times of normal value, the initial dose of methimazole was 30mg/ day, and the thyroid function and antibodies were detected every four weeks. When TSH≥4.2 mIU/L, the amount of methimazole began to decrease, specifically in a daily manner (30 mg→20 mg→15mg). The dose was maintained after the decrease to 15 mg. In the case of hypothyroidism, levothyroxine was added until the three antibodies (TPOAb, TGAb and TRAb) were negative. The dose was maintained for six months, and then the doses of methimazole and levothyroxine were gradually reduced until drug discontinuation (each month). If the initial FT4 was less than 3 times of normal level, the initial dose of methimazole was 15 mg/ day, and levothyroxine was added when hypothyroidism occurred. After all three antibodies were negative, the doses were gradually reduced to the point of drug discontinuation.

Drug: Methimazole

Interventions

Methimazole DRUG

Methimazole used in this study was produced by Merck, Germany, and its trade name is Thyrozol. The specification of this drug is 10mg/ tablet, and its validity period is 36 months. It was approved by FDA in 2009 and listed in China in 2011.

Also known as: Thyrozol

Conventional treatment group; Intensive treatment 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:

• Graves hyperthyroidism (responsible for doctors' clinical diagnosis)
• Age 18-65, for both men and women
• Thyroid receptor antibody (TRAb) was positive
• Take part in this research voluntarily and sign the informed consent form

You may not qualify if:

• Those who have used glucocorticoid or other immunosuppressants for a long time within 3 months before being selected
• Those who have participated in any other drug trials within 3 months before being selected
• Subjects who are participating in clinical research of other drugs
• Patients with a history of malignant tumors
• Ill-controlled hypertension: diastolic blood pressure≥100mmHg, systolic blood pressure ≥160 mmHg
• Blood routine: the total number of white blood cells \< 3.0×109 or neutrophils \< 1.5× 109
• Other thyroid diseases: such as subacute thyroiditis, thyroid nodules, high-function adenoma
• Alanine aminotransferase(ALT) or aspartate amino transferase(AST) is greater than 2 times of the normal upper limit; When ALT or AST is less than 2 times of the normal upper limit, and the test of hepatitis B two half-and-half positive
• Renal insufficiency: serum creatinine is higher than the upper limit of normal value
• Patients with heart failure
• Patients with coronary heart disease
• Patients with other autoimmune diseases
• Patients who are known to be allergic to any component of this medicine are allergic to the active ingredients or any auxiliary materials in the prescription
• Patients with multiple drug allergies, allergic diseases, people with high sensitivity and drug addicts
• Alcoholism, mental disorder or other observers who are not suitable for drug testing

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Nanjing, China

RECRUITING

MeSH Terms

Conditions

Graves Disease; Recurrence; Substance Withdrawal Syndrome

Interventions

Methimazole

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tao Yang

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

• Xuqin Zheng

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Xuqin Zheng

CONTACT

13912902902; zhengxuqin@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: July 18, 2022
• Study Start: May 1, 2018
• Primary Completion: December 31, 2023
• Study Completion (Estimated): July 31, 2030
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)