Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease
Acronym
CIRTED
Study hypothesis
Primary 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).
Study design
Factorial randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Not specified
Study type
Treatment
Patient information sheet
Patient information can be found at: http://www.cirted.org/patients.htm
Condition
Thyroid Eye Disease (TED)
Intervention
All 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 type
Drug
Pharmaceutical study type(s)
Phase
Not Specified
Drug/device/biological/vaccine name(s)
Azathioprine
Primary outcome measure
Primary:
1. Binary composite clinical outcome measure
2. Ophthalmopathy index
Co-primary outcome measure:
1. Clinical activity score
Secondary outcome measures
1. 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 date
01/01/2006
Overall study end date
01/12/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 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
Participant type(s)
Patient
Age group
Adult
Sex
Both
Target number of participants
100
Participant exclusion criteria
1. 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 laboratorys reference range)
14. Abnormal liver function, specifically: bilirubin, alanine aminotransferase or alkaline phosphatase concentrations above the local laboratorys 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
Recruitment start date
01/01/2006
Recruitment end date
01/12/2008
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
Department of Clinical Sciences
Bristol
BS1 2LX
United Kingdom
Sponsor information
Organisation
University of Bristol (UK)
Sponsor details
Research & Enterprise Development
Senate House
Tyndall Avenue
Bristol
BS8 1TH
England
United Kingdom
Sponsor type
University/education
Website
ROR
Funders
Funder type
Research organisation
Funder name
The National Eye Research Centre, Bristol (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Special trustees of Moorfields Eye Hospital (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Charitable Trusts for the United Bristol Hospitals (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
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 |