Clinical trial NCT02126683: The Effect of Plaquenil on Serum Inflammatory Markers and Goiter in Euthyroid Young Women With Hashimoto's Thyroiditis
Official title: The Effect of Plaquenil on Serum Inflammatory Markers and Goiter in Euthyroid Young Women With Hashimoto's Thyroiditis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hashimoto's Thyroiditis
Keywords: Hashimoto's thyroiditis
Plaquenil
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2014-04-30
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change of thyroid auto-antibodies
timeFrame: Baseline, up to 18 months
Secondary outcomes:
measure: Change of inflammatory markers
timeFrame: Baseline, up to 18 months
measure: Change of proinflammatory markers
timeFrame: Baseline, up to 18 months
measure: Change of goiter size
timeFrame: Baseline, up to 18 months
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Tien-Shang Huang
role: PRINCIPAL_INVESTIGATOR
References: