Graves Orbitopathy
Conditions
Keywords
Graves disease, proptosis, antithymocyte globulin
Brief summary
The overall objective of the study is to evaluate the safety and efficacy of rabbit antithymocyte globulin in the treatment of Graves orbitopathy (GO) after ineffective treatment with moderate-to-high doses of glucocorticoids.
Detailed description
This is a prospective interventional, single-center study examining the safety and efficacy of rabbit antithymocyte globulin (rATG) in adult patients with active moderate-to-severe GO after ineffective treatment with moderate-to-high doses of glucocorticoids. All enrolled participants will receive 0.8 - 1.0 mg/kg of rATG (cumulative dose of 150-200 mg given intravenously in two or three divided doses, 24 hours apart) after premedication with methylprednisolone i.v. (in total dose of 375 mg), 1 mg of antihistaminic agent clemastine and 1000 mg paracetamol i.v. In order to assess efficacy and safety of the treatment, patients will be evaluated at baseline and at 6, 12, 24 and 48 weeks. Baseline and subsequent evaluation will involve medical history, physical examination, including detailed eye examination, laboratory assessment (thyroid-stimulating hormone \[TSH\], flow cytometry, TSH-receptor antibodies, CBC) and orbital magnetic resonance imaging (MRI).
Interventions
0.8 - 1.0 mg/kg of rATG (cumulative dose of 150-200 mg given intravenously in two or three divided doses, 24 hours apart) after premedication with methylprednisolone i.v. (in total dose of 375 mg), 1 mg of antihistaminic agent clemastine and 1000 mg paracetamol i.v.
Sponsors
Medical University of Silesia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of Graves' disease associated with active thyroid eye disease and a clinical activity score of ≥ 3 * Euthyroid or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits * previous ineffective treatment (partial response, recurrence or progression of symptoms) with moderate-to-high doses of glucocorticoids (at least 4.5 g of methylprednisolone)
Exclusion criteria
* hypersensitivity to rabbit proteins or to any product excipients * active acute or chronic infections * latent tuberculosis * leucopenia below 3000/μl * lymphopenia below 400/μl * thrombocytopenia below 75000/μl * coagulation disorders * active malignancy and pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ≥2 point change in Clinical Activity Score from baseline | Week 6, 12, 24, 48 |
| change in proptosis | 48 weeks |
| a diplopia response | 48 weeks |
| change of distant best-corrected visual acuity | Week 6, 12, 24, 48 |
| change of mean retinal sensitivity | Week 6, 12, 24, 48 |
Secondary
| Measure | Time frame |
|---|---|
| changes in CD4/CD8 ratio | Week 6, 12, 24, 48 |
| changes in TSH-receptor antibodies level | Week 6, 12, 24, 48 |
| increase in 1 degree amplitude in Pattern visual evoked potential (VEP) by 1 µV | Week 6, 12, 24, 48 |
Countries
Poland
Contacts
Primary ContactGabriela Handzlik, Ph.D.
Outcome results
None listed