The Effect of Plaquenil on Serum Inflammatory Markers and Goiter in Euthyroid Young Women With Hashimoto's Thyroiditis

Hashimoto's thyroiditis (HT) is a common form of autoimmune thyroid disease, which affects up to 2% of general population. The annual incidence of HT worldwide is estimated to be 0.8 - 3.5 cases per 1000 persons. The thyroid gland attacked by a variety of cell- and antibody-mediated immune processes. Various auto-antibodies may be present against TPO and Tg, and ADCC is a substantial factor behind the apoptotic fall-out of HT. Activation of cytotoxic T-lymphocytes in response to cell-mediated immune response affected by helper T-cells is central to thyrocyte destruction. Recent studies showed higher pro-inflammatory cytokines in serum of patients with HT, and suggested HT is associated with regulatory T-cells dysfunction, imbalance of ratio of Th1 cell and Th2 cell, overexpression of Th17 cells.

Several studies suggested that pregnant women with HT, even at euthyroid state had higher risk of spontaneous miscarriage, more frequent post-partum depression and higher depressive, anger, and total mood disturbance risk compared to those without HT. Presence of thyroid auto-antibodies is also associated with negative pregnant outcomes including gestational hypertension, late abortion, fetal death, premature delivery and neonatal respiratory distress. Neonates from mothers with ATD have higher rate of transient hypothyroidism. Children of mothers with ATD had higher risk of positive serum thyroid auto-antibodies and development of goiter and thyroid dysfunction. However, there is no suggested treatment for subjects with HT who have normal thyroid function. Low-iodine diet and regularly follow-up were suggested.

Plaquenil (hydroxychloroquine) is an anti-malarial agent, and has been used to treat several autoimmune diseases, including lupus erythematosus and rheumatoid arthritis for more than a century. It reduced lymphocytes, production of auto-antibodies, cytokines, and immune mediators, NK cell activity, and inhibits antigens presenting to CD4 T-cells of B cells, dendritic cells and monocytes.

This study focuses on the effect of Plaquenil on thyroid auto-antibodies, inflammatory markers, cytokines, and goiter size in euthyroid women with HT.

Study Overview

• Status: Unknown
• Conditions: Hashimoto's Thyroiditis
• Intervention / Treatment: Drug: Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

• Newly diagnosed (within 1 year) Hashimoto's thyroiditis by positive serum anti-TPO antibody or anti-thyroglobulin antibody
• Euthyroid state by serum free T4 and TSH level within normal limit

Exclusion criteria:

• Pregnant, planning pregnant within 1 year, or lactating women
• Renal insufficiency, abnormal liver function test
• Hematologic diseases: anemia, agranulocytosis, thrombocytopenia
• G6PD deficiency, porphyria cutaneous tarda
• Allergy to 4-aminoquinoline compounds
• Known retinopathy or visual field defect disorders
• Already receive immunosuppression therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plaquenil first; Start Plaquenil 200mg BID orally since enrollment Duration: 6 months	Drug: Hydroxychloroquine; Other Names: Plaquenil
Experimental: Plaquenil later; Start Plaquenil 200mg BID orally since the 25th week after enrollment Duration: 6 months	Drug: Hydroxychloroquine; Other Names: Plaquenil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of thyroid auto-antibodies	Change of serum thyroid autoantibodies including anti-TPO antibody and anti-thyroglobulin antibody at baseline, and every 3 months after treatment intervention up to 18 months	Baseline, up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of inflammatory markers	Change of serum inflammatory markers, including hsCRP and ESR at baseline, and every 3 months after treatment intervention up to 18 months	Baseline, up to 18 months
Change of proinflammatory markers	Change of serum proinflammatory markers and cytokine level at baseline, and every 3 months after treatment intervention up to 18 months	Baseline, up to 18 months
Change of goiter size	Change of thyroid volume measured by ultrasound at baseline, and every 3 months after treatment intervention up to 18 months	Baseline, up to 18 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Tien-Shang Huang, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: April 28, 2014
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimate): April 30, 2014

Study Record Updates

• Last Update Posted (Estimate): April 30, 2014
• Last Update Submitted That Met QC Criteria: April 28, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Hashimoto's thyroiditis; Plaquenil
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Thyroiditis, Autoimmune; Hashimoto Disease; Thyroiditis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 201312121MINA