Adjuvant Treatment of Graves´ Ophthalmopathy With NSAID (aGO Study)

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mikael Lantz
• Treatments: Diclofenac; Methimazole; Metoprolol; Propranolol

Criteria

Inclusion Criteria:

1. Graves thyrotoxicosis ( with clinical symptoms)

2. Age 18 - 75 year

3. TSH = 0.2 or < 0.2 and increased fT4 and/or fT3

4. Signed informed consent

Exclusion Criteria:

1. Pregnancy or breastfeeding, women in childbearing age should use non- barrier contraceptives

2. Previous treatment of thyroid disease

3. Thyrostatics before radioiodine treatment

4. Hypersensitivity to NSAID or ASA

5. Congestive heartfailure

6. Impaired renal function defined as p-creatinine > 100 mmol/L

7. ASAT or ALAT > 2.5 times the upper limit

8. Alcoholism

9. Coagulopathy including warfarin treatment

10. Thrombocytopenia

11. Previous or active gastric ulcera

12. Inflammatory bowel disease