Function of Regulatory T Cells Improved by Dexamethasone in Graves' Patients

NCT01534169 | Completed Phase 1 DMC

• 1 other identifier: HDJP-H200829
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Antithyroid drugs is the first choice treatment of Graves' disease in China and Europe. However,the relapse rate is very high (40-60%) after therapy withdrawal, and many patients need further treatment. In our previous study, a new treatment strategy for GD has been introduced. After methimazole (18 months) combined with intrathyroid injection of dexamethasone (DEX) (3 months) treatment, the relapse rate of hyperthyroidism was markedly reduced compared with methimazole treatment alone (7.4% versus 51%) during the 2-year follow-up period. The results have been published in the 'J Clin Endocrinol Metab, 2009,94:4984-4991'. However, the mechanism by which the DEX reduces the relapse rate of GD is not fully understood. In vitro study, we have proven that DEX could effectively improve the function of regulatory T (Treg) cells and set up a new balance of T helper 1(Th1)/Th2 in GD patients(this results have been in press in the Eur J Endocrinol). In order to elucidate mechanism of this treatment strategy in vivo, we plan to recruit 20-30 patients with GD and treat those patients by intrathyroid injection of DEX combined with methimazole, and the function of Treg cells and balance of Th1/Th2 will be evaluated.

Conditions

Graves' Disease

Keywords

Graves' disease; Dexamethasone; Function of regulatory T cells; The proportion of Th1 and Th2 cells

Outcome Measures

Primary Outcomes (1)

• Function of Regulatory T Cells

  Function of Treg cells will be analyzed by the proliferation rate of CD4+CD25- T cells, according to the following formula: cell proliferation rate (%) = proliferation rate of CD4+CD25- T cells co-cultured with CD4+CD25+T cells/proliferation rate of CD4+CD25- T cells alone×100%.

  From baseline to 90 days

Secondary Outcomes (1)

• The proportion of Th1 and Th2 cells

  From baseline to 90 days

Study Arms (1)

Isotonic Na chloride

EXPERIMENTAL

The treatment strategy is the same with intervention, only the drug (dexamethasone) will be changed to isotonic Na chloride.

Drug: Dexamethasone

Interventions

Dexamethasone DRUG

The course of treatment will be last for 3 months. The intrathyroid injection of dexamethasone will be performed using a 25-gauge (0.25-mm) needle under ultrasound guidance. The injection will be performed in both lobes of the thyroid. The dosage of dexamethasone is 5mg (1.0 ml) in each lobe, twice a week during the first month of the treatment. The treatment strategy will be changed to once a week in the second month and twice a month in the third month; the dosage of dexamethasone is the same as in the first month.

Also known as: Hexadecadrol

Isotonic Na chloride

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• GD patients will have been trated with methimazole and serum levels of TSH and FT4 should be in the normal range.

You may not qualify if:

• Pregnancy
• Allergy to antithyroid drugs (ATD)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than two times the upper normal range
• Patients with coexistent endocrine or organ-specific autoimmune diseases (such as those with atopic dermatitis or bronchial asthma)
• Patients taking medications that could affect the immune system (such as corticosteroids), noncompliance because of psychiatric or other serious diseases
• Unwillingness to participate in the study.

Sponsors & Collaborators

• Xiao-Ming Mao: lead

Study Sites (1)

Nanjing First Hospital Affiliated to Nanjing Medical University

Nanjing, Jiangsu, 210006, China

Location

Related Publications (2)

• Mao XM, Li HQ, Li Q, Li DM, Xie XJ, Yin GP, Zhang P, Xu XH, Wu JD, Chen SW, Wang SK. Prevention of relapse of Graves' disease by treatment with an intrathyroid injection of dexamethasone. J Clin Endocrinol Metab. 2009 Dec;94(12):4984-91. doi: 10.1210/jc.2009-1252. Epub 2009 Oct 22.

  PMID: 19850691 RESULT

• Hu Y, Tian W, Zhang LL, Liu H, Yin GP, He BS, Mao XM. Function of regulatory T-cells improved by dexamethasone in Graves' disease. Eur J Endocrinol. 2012 Apr;166(4):641-6. doi: 10.1530/EJE-11-0879. Epub 2012 Jan 4.

  PMID: 22219499 RESULT

MeSH Terms

Conditions

Graves Disease

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Xiao-Ming Mao, MD.

  Nanjing First Hospital Affiliated to Nanjing Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD.

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 16, 2012
• Study Start: March 1, 2012
• Primary Completion: March 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 12, 2012

Record last verified: 2012-11

Locations

CN (1)