Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease

ISRCTN ISRCTN22471573
DOI https://doi.org/10.1186/ISRCTN22471573
Secondary identifying numbers N/A
Submission date
25/01/2006
Registration date
01/02/2006
Last edited
14/02/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Eye Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Mr Richard Lee
Scientific

Department of Clinical Sciences
Bristol Eye Hospital
Lower Maudlin street
Bristol
BS1 2LX
United Kingdom

Study information

Study designFactorial randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Participant information sheet Patient information can be found at: http://www.cirted.org/patients.htm
Scientific titleCombined Immunosuppression and Radiotherapy in Thyroid Eye Disease
Study acronymCIRTED
Study objectivesPrimary hypotheses:
To test the following hypotheses in patients being treated with prednisolone for active Thyroid Eye Disease (TED):
1. Radiotherapy (compared with placebo) induces early remission and reduces long-term disease severity
2. Combined systemic immunosuppression with oral azathioprine (compared with placebo) reduces long-term disease severity

Secondary hypotheses:
1. To test the hypothesis that patients being treated with prednisolone for active TED, using radiotherapy and combined systemic immunosuppression with oral azathioprine, can improve patient-centred outcomes and quality of life scores
2. To validate the use of a new TED specific quality of life score in the UK population
3. To improve understanding of the extent and type of psychosocial distress experienced by TED patients
4. To conduct an economic evaluation of the cost of TED and its treatment to patients, the NHS and Society
5. To compare treatments using health-economic analysis
6. To report the safety and tolerability of combined systemic immunosuppression with oral azathioprine in TED patients
Ethics approval(s)Central & South Bristol Research Ethics Committe (reference: 05/Q2006/62), approval gained 5th May 2005 (amendment to inclusion and exclusion criteria approved on the 2nd June 2006).
Health condition(s) or problem(s) studiedThyroid Eye Disease (TED)
InterventionAll the patients receive six months of oral prednisolone and then are randomly assigned to receive one of the following interventions:
1. Radiotherapy and azathioprine
2. Radiotherapy and placebo
3. Azathioprine and placebo
4. Control: placebo and placebo
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Azathioprine
Primary outcome measurePrimary:
1. Binary composite clinical outcome measure
2. Ophthalmopathy index

Co-primary outcome measure:
1. Clinical activity score
Secondary outcome measures1. Total Eye Score (TES)
2. Hospital Anxiety and Depression Scale (HADS) score
3. Derriford Appearance scale-short form score
4. Graves’ Ophthalmopathy Quality of Life (GO-QoL) score
5. World Health Organisation Brief Quality of Life (WHOQoL) assessment score
6. Open-ended responses to interview questions
7. Health economic measures
Overall study start date01/01/2006
Completion date01/12/2008

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants100
Key inclusion criteria1. Mourits' Clinical Activity Score more than or equal to four (worst eye) or more than two (worst eye) with a history of proptosis (defined as either subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of more than 2 mm or subjective bilateral proptosis) or motility restriction (defined as intermittent, inconstant or constant diplopia grade) which is less than six months long
2. Past or present history of abnormal Thyroid Gland Function (TGF) or a clinical diagnosis of TED made and confirmed by more than two muscle involvement on Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan plus a history of recent onset motility restriction and/or proptosis
Key exclusion criteria1. Age less than 20 or greater than 75 years
2. Optic neuropathy
3. Mourits’ Clinical Activity Score more than four without proptosis or motility restriction
4. Pre-existing glaucoma with a characteristic optic disc appearance and associated visual field defect
5. Use of radioiodine within the last three months
6. Pre-existing diabetes mellitus (not simply steroid-induced disease from recent therapy)
7. Previous adverse event associated with, or contraindication to, either prednisolone or azathioprine
8. Within six months of pregnancy, women planning pregnancy
9. Lactation
10. Haemoglobin concentration, total white cell count or platelet count below the local laboratory's reference range
11. Low, intermediate or high Thiopurine Methyltransferase (TPMT) activity
12. Lymphocyte count less than 0.8 x 10^9/l
13. Abnormal renal function (assessed by urea and creatinine levels above the local laboratory’s reference range)
14. Abnormal liver function, specifically: bilirubin, alanine aminotransferase or alkaline phosphatase concentrations above the local laboratory’s reference range
15. Malignant or pre-malignant (dysplastic) condition within the past five years
16. Previous tuberculosis
17. Shingles within the past three months
18. Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
19. Concurrent use of:
a. Other immunosuppressive or cytotoxic agents
b. Allopurinol
20. Live vaccines within the past three months
21. Previous orbital irradiation
Date of first enrolment01/01/2006
Date of final enrolment01/12/2008

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Department of Clinical Sciences
Bristol
BS1 2LX
United Kingdom

Sponsor information

University of Bristol (UK)
University/education

Research & Enterprise Development
Senate House
Tyndall Avenue
Bristol
BS8 1TH
England
United Kingdom

ROR logo "ROR" https://ror.org/0524sp257

Funders

Funder type

Research organisation

The National Eye Research Centre, Bristol (UK)

No information available

Special trustees of Moorfields Eye Hospital (UK)

No information available

The Charitable Trusts for the United Bristol Hospitals (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 31/01/2008 Yes No
Results article results 01/04/2018 Yes No

Editorial Notes

14/02/2018: Publication reference added.