Comparison of the Effectiveness of Two Glucocorticoid Regimens for Treatment of Graves' Orbitopathy

Comparison of the Efficacy of Two Different Glucocorticoid Regimens for Treatment of Active Moderate-to-severe Graves' Orbitopathy

The goal of this interventional study is to compare the effectiveness of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy. The main questions it aims to answer are:

1. Are the two glucocorticoid regimens similarly effective?
2. Do the two glucocorticoid regimens have similar safety profile? The patients involved are treated with one of the two glucocorticoid regimens. Their ocular status, therapeutic response and quality of life reassessed during the treatment, at its end, and 3 month later.

Study Overview

• Status: Completed
• Conditions: Graves Ophthalmopathy
• Intervention / Treatment: Drug: Methylprednisolone

Detailed Description

Systemic glucocorticoids are the mainstay of treatment for active moderate-to-severe Graves' orbitopathy. However, there are a number of different glucocorticoid regimens with different total dosage, schemes of administration and duration. The goal of this interventional study is to compare the effectiveness of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy. The main questions it aims to answer are:

1. Are the two glucocorticoid regimens similarly effective?
2. Do the two glucocorticoid regimens have similar safety profile? The patients involved are treated with one of the two glucocorticoid regimens. The first group is treated with modified monthly regimen, including 3 pulses of 3 infusions of 500 mg methylprednisolone administered in three consecutive months, with application of 125 mg methylprednisolone intramuscularly once per week between the pulses. Total cumulative dose - 5.5. g., duration - 3 months. After completion of the venous infusions, a low dose peroral glucocorticoid therapy is prescribed for the next 3 months. The second group is treated with weekly glucocorticoid regimen: 6 infusions of 500 mg methylprednisolone during the first 6 weeks followed by 6 infusions of 250 mg methylprednisolone during the next 6 weeks. Total cumulative dose - 4.5 g., duration - 3 months. Patients' ocular status and therapeutic response are assessed at 1st, 3rd and 6th months; quality of life - at 3rd and 6th month.

• Study Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1000
    • University Hospital of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Sixty-two patients with untreated active moderate-to-severe Graves' orbitopathy in euthyroid state under treatment.

Description

Inclusion Criteria:

• Active moderate-to-severe Graves' orbitopathy
• Without previous treatment with glucocorticoids or orbital radiotherapy
• Euthyroid state

Exclusion Criteria:

• Uncontrolled hyper- or hypothyroidism
• Previously treated Graves' orbitopathy
• Mild or sight-threatening form of Graves' orbitopathy
• Inactive moderate-to-severe Graves' orbitopathy
• Contraindications for glucocorticoid treatment

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Modified monthly regimen; Treatment with 3 pulses of 3 infusions of 500 mg methylprednisolone on 3 consecutive months with intramuscular administration of 125 mg methylprednisolone per week between the pulses. Additional low dose peroral treatment after completion of the pulses.	Drug: Methylprednisolone; methylprednisolone applied as intravenous infusions or intramuscularly; Other Names: Urbason
Weekly regimen; Treatment with 6 infusions of 500 mg methylprednisolone during the first 6 weeks, followed by 6 infusions of 250 mg methylprednisolone during the next 6 weeks.	Drug: Methylprednisolone; methylprednisolone applied as intravenous infusions or intramuscularly; Other Names: Urbason

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the changes in the overall therapeutic response assessed using Bartalena's criteria during the treatment with the two glucocorticoid regimens	Comparison of the changes in the overall therapeutic response assessed using Bartalena's criteria and classified as full, partial and no response during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in clinical activity score, assessed using a 7- or 10-point scale and expressed in points during the treatment with the two glucocorticoid regimens	Comparison of the changes in clinical activity score, assessed using a 7-point scale at baseline or 10-point scale during the follow-up and expressed in points as recommended by European Thyroid Association and European Group on Graves' orbitopathy during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in lid aperture expressed in mm during the treatment with the two glucocorticoid regimens	Comparison of the changes in lid aperture measured by ruler and expressed in mm during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in proptosis expressed in mm during the treatment with the two glucocorticoid regimens	Comparison of the changes in proptosis measured by Hertel's exophthalmometer and expressed in mm during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in visual acuity expressed in decimals during the treatment with the two glucocorticoid regimens	Comparison of the changes in visual acuity measured by Snellen chart and expressed in decimals during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in diplopia assessed using Gorman's classification system during the treatment with the two glucocorticoid regimens	Comparison of the changes in diplopia assessed using Gorman's classification system and classified as gr. 0 absent, gr. I intermittent, gr. II inconstant, gr. III constant during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in soft tissue involvement evaluated using the colour atlas proposed by European Group on Graves' orbitopathy during the treatment with the two glucocorticoid regimens	Comparison of the changes in soft tissue involvement evaluated using the colour atlas proposed by European Group on Graves' orbitopathy and categorized as gr. 0-I absent or mild, gr. II-III moderate or severe during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in subjective symptoms whose severity was reported by patients themselves using subjective scale during the treatment with the two glucocorticoid regimens	Comparison of the changes in subjective symptoms whose severity was reported by patients themselves and were graded as 0-I absent or mild, gr. II-III moderate or severe during the treatment with the two glucocorticoid regimens	6 months
Comparison of the changes in quality of life assessed by disease-specific questionnaire recommended by European Group on Graves' orbitopathy (GO-QoL) аnd expressed as percentages during the treatment with the two glucocorticoid regimens	Comparison of the changes in quality of life during the treatment with the two glucocorticoid regimens assessed by disease-specific questionnaire recommended by European Group on Graves' orbitopathy (GO-QoL) аnd expressed as percentages, which includes two subscales - one evaluating the impact of Graves' orbitopathy on patients' visual functioning (QoL-VF) and the other related to the changes of physical appearance as a result of the disease (QoL-AP)	6 months
Incidence of treatment-emerged adverse events in the two glucocorticoid regimens groups	Number and type of adverse reactions in the study groups reported by patients themselves or found by the laboratory tests or during clinical examination.	6 months

Collaborators and Investigators

• Sponsor: Medical University of Sofia
• Investigators: Principal Investigator: Mariya D Stoynova, PhD, Medical University of Sofia: Medicinski universitet-Sofia

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): February 25, 2021

Study Registration Dates

• First Submitted: March 7, 2023
• First Submitted That Met QC Criteria: March 29, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: 21A /25.07.2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No