In this study, we want to demonstrate that MPP is no less effective than MPP plus XRT.
ID
Source
Brief title
Condition
- Ocular structural change, deposit and degeneration NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Change in vertical lid aperture * 2mm
2. Change in NOSPECS grade 2 with 2 degrees (e.g. 2c to 2a)
3. Change in proptosis * 2 mm
4. Change in (any) duction * 8 degrees
5. Change in Gorman score * 1 level
6. Change in CAS * 2 points
Endpoints are defined as:
Improvement: change of * 2 parameters in at least one eye, without
deterioration of any parameter in the contralateral eye
Deterioration: deterioration in * 2 parameters in one or both eyes or
development of new onset DON
Unchanged: no changes or change in any of the parameters smaller than
defined above
Secondary outcome
1. Change of Goldmann field of BSV at 6 and 12 months
2. Change of GO-QOL at 6 and 12 months
Background summary
Graves* disease (GD) is an autoimmune disorder that may affect the thyroid
gland (Graves* thyroid disease), the orbit (Graves* orbitopathy, GO) and the
pretibial skin (Graves* dermopathy). The incidence of GO in the USA and in
Denmark is calculated around 40:100.000 in women and 8:100.000 in men (1,2). In
Europe, 1% of the women between 35-60 years are supposed to suffer from GD and
half of them from GO (3).
Symptoms vary from eyelid retraction and eyelid swelling to protrusion of the
eyes, eye motility restriction with diplopia, corneal ulceration and visual
impairment resulting from optic nerve compression. Untreated, 3-5% of the
patients become blind as a result of the latter two manifestations (4).
Moreover, GO may cause severe facial cosmetic deformities.
GO is caused by an autoimmune mediated inflammation and swelling of the orbital
muscles, followed by an increase of the orbital fat (5). The initial active
phase of the disease is characterized by an increase of the severity of the
symptoms. Even without treatment, this active phase sooner or later (after
months to years) is followed by a burnt out phase in which the disease has
become quiescent, but in which symptoms as proptosis or motility restriction
may persist (6). In mild cases, a wait and see policy can be justified and
persisting complaints like eyelid retraction can be surgically dealt with in
the quiesent stage.
Consensus exists as how to treat patients with active and more severe or vision
threatening GO (7). They are treated with intravenously administered high dose
methylprednisolon (i.v. MPP) (8). Aim of this intervention is to reduce or
erase symptoms of disease activity such as soft tissue swelling, prevent
progression, reduce the need of successive surgery and allow surgery, if
necessary, in an earlier stage of the disease (9). Several RCT*s have shown,
that MPP is effective in 60 to 80%, but certainly not in all patients with GO
(8,9).
Other studies demonstrated that the combination of external beam irradiation
(XRT) and prednisone treatment might be more effective than each of them alone
(11,12). Even low doses XRT have shown to be effective and side effects are
limited (13). XRT is thought to inactivate the orbital fibroblast, which play a
key role in the etiology of GO (14). XRT may sustain the improvement initiated
by prednisone (15). XRT, however, implies 12 visits to the department of
radiotherapy plus extra costs.
The combination of prednison and XRT has been studied in patients receiving
oral corticosteroids (11,12), but not yet in patients receiving MP. As MPP
offers significant benefits over oral steroid therapy (more effective, less
side-effects), it is at present the treament of choice. There is, however, a
worldwide tendency to prescribe XRT together with MPP, although its advantages
have not been demonstrated yet.
Study objective
In this study, we want to demonstrate that MPP is no less effective than MPP
plus XRT.
Study design
Non-blinded parallel group intervention study
Intervention
One group receives both iv CS and XRT, the other only iv CS
Study burden and risks
In 1-2% of patients receiving radiotherapy mild retinopathy can occur.
There is a theoretical chance of cancer formation due to the radiotherapy, but
the chance is very slim due to the small area receiving a small amount of
radiotherapy
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Active Graves' Orbitopathy (GO):
- onset less than 12 months, and
- CAS * 3 out of 7 or 4 out of 10
2. Moderately severe GO:
- NOSPECS grade 2b or c, and/or
- Severe proptosis (in women * 20mm and in men * 22 mm), and/or
- Motility restriction defined as a duction < 30 degrees in either abduction, adduction, elevation or depression, and/or
- Gorman/Bahn score of C (Gorman/Bahn score: A.no diplopia; B. intermittent; C. inconstant; D: constant)
3. Clinically and biochemically euthyroidism for at least 6 weeks
Exclusion criteria
1. Unable or unwilling to provide informed consent
2. Age <35 years or >75
3. Diabetes mellitus
4. Mild GO
5. Presence of dysthyroid optic neuropathy (DON)
6. Previous orbital surgery or radiotherapy for GO.
7. Corticosteroid or immunotherapy (on average > 20mg daily) for GO within previous 3 months
8. Pre-existent strabismus
9. Patients with amblyopia or with functional monocular vision making it impossible to measure diplopia and/or strabismus
10. Patients with pre existent glaucoma with severe visual field defects
11. Pregnancy
12. Unfit for corticosteroid therapy as decided by endocrinologist
13. Abnormal liver function (factor 2 above normal values)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL60905.018.17 |