Orbital Radiotherapy in Grave's Ophthalmopathy 1 Week vs 2 Weeks (OraGO-1 Trial)

Thyroid Associated Ophthalmopathy Clinical Trial

Official title:

Orbital Radiotherapy in Grave's Ophthalmopathy 1 Week vs 2 Weeks: A Phase II Randomized Controlled Trial (OraGO-1 Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06392906
• Other study ID #: SI208/2024
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2024
• Est. completion date: October 31, 2028

Study information

• Verified date: April 2024
• Source: Mahidol University
• Contact: Janjira Petsuksiri, M.D.
• Phone: 66919966662
• Email: janjira.pet[@]mahidol.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Thyroid ophthalmopathy, also known as thyroid eye disease or Graves' ophthalmopathy, is a condition characterized by inflammation and swelling of the tissues around the eyes, often accompanied by protrusion of the eyeballs. This condition can lead to significant discomfort, visual disturbances, and in severe cases, permanent vision loss. Primary treatment modalities are intravenous methylprednisolone (IVMP) and other medications for patients with moderate to severe and active thyroid eye disease. In addition, external beam radiation therapy (ERT) is an another treatment option in combination with IVMP. Radiation therapy delivers targeted doses of ionizing radiation to the affected orbital tissues, effectively reducing inflammation. This approach is particularly beneficial for patients who may not respond adequately to steroid therapy alone or those who experience recurrent disease flares. This study will test the efficacy of a shortened treatment regimen comprising 5 sessions of ERT to a standard protocol of 10 treatments. The primary aim is to ascertain the effectiveness of shorted radiation treatment while improving patients' quality of life.

Description:

The research methodology of this study involves comparing the standard protocol of 10 radiation treatments with a modified approach comprising 5 treatments of daily External Beam Radiation Therapy (ERT). The primary objective of this investigation is to assess whether reducing the number of radiation treatments while maintaining the effectiveness of the therapy can lead to improvements in the quality of life for patients with thyroid ophthalmopathy. By comparing these two treatment regimens, researchers aim to evaluate the efficacy and safety of the abbreviated radiation schedule in managing the symptoms and progression of the disease. Participants enrolled in the study will be randomized into two groups: one receiving the standard 10 treatments and the other receiving the modified 5-treatment regimen of daily ERT. Throughout the study period, participants will undergo comprehensive assessments to monitor changes in symptoms, vision, and quality of life. These evaluations will include ophthalmic examinations, imaging studies, and patient-reported outcome measures to capture both objective and subjective measures of treatment response.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 68
• Est. completion date: October 31, 2028
• Est. primary completion date: April 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patient with active moderate to severe thyroid eye disease with a CAS > 4 with/ without diplopia before starting IVMP
• Patient with poor response to 3 doses of IVMP (CAS drop < 1) ???? CAS score > 3 after 3 doses of IVMP
• Patients with diplopia after 3 doses of IVMP
• Patients with Graves' Ophthalmopathy who have maintained euthyroidism
• Non-pregnant adults (aged 35 years or older)

Exclusion Criteria:

• Individuals with severe hypertension or diabetic retinopathy

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Associated Ophthalmopathy

Intervention

Radiation:
• Short course radiation therapy
5 daily radiation treatments
• Standard course radiation therapy
10 daily radiation treatments

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Siriraj Hospital Mahidol University	Bangkok Noi

Sponsors (2)

Lead Sponsor	Collaborator
Janjira Petsuksiri	Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (11)

Abdus-Salam AA, Olabumuyi AA, Jimoh MA, Folorunso SA, Orekoya AA. The role of radiation treatment in the management of inflammatory musculoskeletal conditions: a revisit. Radiat Oncol J. 2020 Sep;38(3):151-161. doi: 10.3857/roj.2020.00178. Epub 2020 Jun 1 — View Citation

Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marino M, Vaidya B, Wiersinga WM; EUGOGO dagger. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. — View Citation

Hoang TD, Stocker DJ, Chou EL, Burch HB. 2022 Update on Clinical Management of Graves Disease and Thyroid Eye Disease. Endocrinol Metab Clin North Am. 2022 Jun;51(2):287-304. doi: 10.1016/j.ecl.2021.12.004. Epub 2022 May 11. — View Citation

Johnson KT, Wittig A, Loesch C, Esser J, Sauerwein W, Eckstein AK. A retrospective study on the efficacy of total absorbed orbital doses of 12, 16 and 20 Gy combined with systemic steroid treatment in patients with Graves' orbitopathy. Graefes Arch Clin E — View Citation

Kahaly GJ, Rosler HP, Pitz S, Hommel G. Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial. J Clin Endocrinol Metab. 2000 Jan;85(1):102-8. doi: 10.1210/jcem.85.1.6257. — View Citation

Kim M, Chang JH, Lee NK. Quantitative analysis of extraocular muscle volume and exophthalmos reduction after radiation therapy to treat Graves' ophthalmopathy: A pilot study. Eur J Ophthalmol. 2021 Mar;31(2):340-345. doi: 10.1177/1120672119873841. Epub 20 — View Citation

Lumyongsatien M, Keeratidamkerngsakul B, Pornpanich K, Vangveeravong S, Saonanon P, Wiwatwongwana D, Mahaisavariya P, Aryasit O, Pongpirul K. Development and psychometric properties of the Thai Graves' ophthalmopathy quality of life (GO-QOL) questionnaire — View Citation

Marcocci C, Bartalena L, Bogazzi F, Bruno-Bossio G, Lepri A, Pinchera A. Orbital radiotherapy combined with high dose systemic glucocorticoids for Graves' ophthalmopathy is more effective than radiotherapy alone: results of a prospective randomized study. — View Citation

San Miguel I, Arenas M, Carmona R, Rutllan J, Medina-Rivero F, Lara P. Review of the treatment of Graves' ophthalmopathy: The role of the new radiation techniques. Saudi J Ophthalmol. 2018 Apr-Jun;32(2):139-145. doi: 10.1016/j.sjopt.2017.09.003. Epub 2017 — View Citation

Torres Royo L, Antelo Redondo G, Arquez Pianetta M, Arenas Prat M. Low-Dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother. 2020 Mar-Apr;25(2):250-254. doi: 10.1016/j.rpor.2020.02.004. Epub 2020 Feb 22. — View Citation

Weissmann T, Lettmaier S, Donaubauer AJ, Bert C, Schmidt M, Kruse F, Ott O, Hecht M, Fietkau R, Frey B, Putz F. Low- vs. high-dose radiotherapy in Graves' ophthalmopathy: a retrospective comparison of long-term results. Strahlenther Onkol. 2021 Oct;197(10 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Activity Score (CAS) change	To evaluate the non-inferiority of outcomes in terms of the patient's proportion of converting from active (CAS > 4) to inactive eye disease (CAS <3) with CAS drop > 2 points, following orbital radiotherapy in combination with IVMP, comparing standard and reduced-dose orbital radiotherapy; CAS score range from 1-7, initially and range from 1-10 at 1-3 months follow-up period. Higher CAS scores represented worse outcomes.	6 months after initiation of IVMP
Secondary	muscle and retrobulbar fat volume change	To compare the change in volume of extra-ocular muscles and retro bulbar fat after orbital radiotherapy, comparing standard with reduced-dose orbital radiotherapy	6 months after initiation of IVMP
Secondary	change in diplopia	To compare the difference in prism deviation in primary gaze after standard and reduced-dose orbital radiotherapy	6 months after initiation of IVMP
Secondary	change in quality of life	To compare the difference in Graves' ophthalmopathy quality of life (GO-QOL) scores (Thai version) between standard and reduced-dose orbital radiotherapy. The total QOL scores range from 0 to 100 with higher scores indicating a better health status.	6 months after initiation of IVMP
Secondary	Radiation toxicities	To compare the summation of the Radiation Therapy Oncology Group (RTOG) toxicity scores (including dry eye, eye pain, keratitis, eyelid, conjunctiva, lacrimal gland, cornea, iris and skin toxicities) after standard and reduced-dose orbital radiotherapy. The RTOG gradings range from grade 0 to grade 4 in each item. The total toxicity scores range from 0-34, with a higher score indicating more severe side effects.	6 months after initiation of IVMP
Secondary	Visual acuity (VA)	-To compare the differences in visual acuity (logMAR) change after standard and reduced-dose orbital radiotherapy	6 months after initiation of IVMP
Secondary	Visual field (VF)	- To compare the differences of Humphrey's visual field (mean deviation) change after standard and reduced-dose orbital radiotherapy	6 months after initiation of IVMP