99Tc-MDP for Thyroid-Associated Ophthalmopathy

A Double-masked, Methylprednisolone-control, Efficacy and Safety Study of 99Tc-MDP for Thyroid Associated Ophthalmopathy.

To investigate the efficacy，safety and tolerability of 99Tc-MDP in comparison to Methylprednisolone, in the treatment of participants suffering from active moderate to severe TAO.

Study Overview

• Status: Completed
• Conditions: Thyroid-Associated Ophthalmopathy
• Intervention / Treatment: Drug: Methylprednisolone; Drug: 99Tc-MDP(99Technetium-Methylenediphosphonate Injection)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Affiliated Zhongshan Hospital of Dalian University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient age 18 Years to 76 Years;
• Fewer than 6 months from onset of TAO;
• Clinical diagnosis of Graves' disease associated with active TAO and a clinical activity score of ≥ 3;
• Moderate to severe TAO;
• No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization.

Exclusion Criteria:

• Optic neuropathy, severe orbital appearance and surgical;
• Extra-thyroid disease;
• Pregnant and children;
• Severe impairment of cardiac, hepatic and renal functions;
• Allergies;
• Other contraindications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylprednisolone(ivMP); Methylprednisolone(ivMP) 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. once a week for 6 weeks.	Drug: Methylprednisolone; 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. once a week for 6 weeks.
Experimental: 99Tc-MDP; 99Tc-MDP 15mg i.v. infusion once a day for 10 days, 20 days apart, received 3 courses of infusions.	Drug: 99Tc-MDP(99Technetium-Methylenediphosphonate Injection); 15mg i.v. infusion once a day for 10 days, 20 days apart, received 3 courses of infusions.; Other Names: Yunke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Status at Week 12	This end point main evaluation improvement of clinical activity score and proptosis at week 12. A reduction of the CAS 2 point or more, and reduction of the proptosis 2 mm or more was defined as response.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Average Continuous Change in CAS From Baseline to Week 24	The 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amended CAS was used to evaluate clinical activity. CAS of 3 point or more on a 7-point scale indicating active thyroid-associated ophthalmopathy.	Baseline to Week 24
Overall Average Continuous Change in Proptosis From Baseline to Week 24	Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements were recorded with the Hertel exophthalmometer.	Baseline to Week 24
Overall Average Change in Diplopia grading From Baseline to Week 24	Diplopia grading included 01/4no：no diplopia; 11/4intermittent： diplopia in primary position of gaze, when tired or when first awakening; 21/4inconstant： diplopia at extremes of gaze; 31/4constant： continuous diplopia in primary or reading position). Diplopia change in one grade or more at week 24 was regarded as improvement.	Baseline to Week 24
Overall Average Change in extra-ocular muscular thickening From Baseline in thickening extra-ocular muscular improvement in Orbital CT to Week 24	Observation of extra-ocular muscular thickening is observed on Orbital CT. One or more extra-ocular muscle recovery at week 24 was regarded as improvemed.	Baseline to Week 24
Overall Average Change in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale From baseline to Week 24 follow-up	The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of thyroid associated ophthalmopathy (TAO) by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale.The transformed overall score is the sum of scores from all 16 questions to a scale of 0 (worst health) to 100 (best health). A change of 8 point was defined as improvement.	Baseline to Week 24
Overall Average Change in GO-QOLScale - Visual Functioning From baseline to Week 24 follow-up	Transformed Visual Functioning score is the sum of scores from following 8 questions to a scale of 0 (worst health) to 50 (best health): bicycling, driving, moving around the house, walking outdoors, reading, watching television (TV), hobby or pastime, feel hindered.	Baseline to Week 24
Overall Average Change in GO-QOLScale - Appearance From baseline to Week 24 follow-up	Transformed Appearance score is the sum of scores from the following 8 questions to a scale of 0 (worst health) to 50 (best health): feel appearance has changed, feel being stared at, feel people react unpleasantly, influence on self-confidence, feel socially isolated, influence on making friends, appear less often on photos, try to mask changes in appearance.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Dalian University

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2017
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: safety; efficacy; 99Tc-MDP; TAO
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; 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; Radiopharmaceuticals; Bone Density Conservation Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Methylene diphosphonate; Technetium Tc 99m Medronate
• Other Study ID Numbers: zsyy_nfm2-2017-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No