Adjuvant Treatment of Graves´ Ophthalmopathy With NSAID (aGO Study)
Status:
Completed
Trial end date:
2016-02-01
Target enrollment:
Participant gender:
Summary
AGO study - adjuvant treatment, with NSAID, of endocrine ophthalmopathy in Graves´ disease
Background - Already at diagnosis of Graves disease approximately 98% of the patients have
morphological changes of the retrobulbar tissue concordant with ophthalmopathy. Factors known
to induce clinical symptoms of ophthalmopathy are mainly unknown. An interesting observation
is that a patient with stable and inactive Graves´ disease developed ophthalmopathy when
treated with a glitazone due to diabetes type 2. Glitazones have been shown to increase
differentiation of orbital preadipocytes to mature adipocytes. Glitazones are PPAR-gamma
agonists and recently diclofenac have been shown to interact with PPAR-gamma in physiological
concentrations. Other non-steroidal antiinflammatory drugs, NSAID, like indomethacin lack
this effect. In addition, diclofenac inhibit synthesis of prostaglandins which also may be of
importance because the natural ligand to PPAR-gamma is prostaglandin J. Inflammation and
adipogenesis are hallmarks of the pathological process in Graves ophthalmopathy and NSAID
like diclofenac may affect both. There is only one earlier study demonstrating effects of
NSAID (indomethacin) in 7 patients with effects on soft tissue symptoms, eye muscle symptoms
and eye protrusion.
Aim - to investigate if diclofenac can prevent ophthalmopathy and/or progress of
ophthalmopathy.
Specific aims:
1. To study the frequency of clinical ophthalmopathy in Graves´ disease after 12 months
treatment with or without diclofenac.
2. To study the frequency of progress of clinical signs and symptoms in ophthalmopathy
after 12 months treatment with or without diclofenac.
3. To study the frequency of optic neuropathy in clinical ophthalmopathy after 12 months
treatment with or without diclofenac.
Study plan and randomisation -
150 patients with newly diagnosed Graves´disease without ophthalmopathy will be treated with
anti-thyroid drugs and L-thyroxin (block and replace) according to clinical routine for 18
months. These patients will be randomized to diclofenac 50 mg twice daily or not for 12
months.