NCT01458600: aGO

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

Completed Phase 4 Last updated 23 February 2016

What this trial tests

Phase 4 trial testing Diclofenac in Graves´ Disease in 65 participants. Completed in 1 February 2016.

Timeline

1 September 2006

Primary endpoint
1 February 2016

1 February 2016

Quick facts

Lead sponsor	Mikael Lantz
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	65
Start date	1 September 2006
Primary completion	1 February 2016
Estimated completion	1 February 2016
Sites	3 locations across Sweden

Drugs / interventions tested

• Diclofenac (DICLOFENAC) — full drug profile →
• Methimazole — full drug profile →
• L-thyroxin — full drug profile →
• Propranolol (propranolol) — full drug profile →
• Metoprolol (metoprolol) — full drug profile →

Conditions studied

• Graves´ Disease — all drugs for Graves´ Disease →

Sponsor

Mikael Lantz

Who can join

Adults 18 to 75, any sex, with Graves´ Disease. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• The frequency of ophthalmopathy after 24 months as judged by the following clinical signs
  Time frame: 24 months
  Optic nerve dysfunction 0. No 1. Yes Eye-lid edema 0. No 1. Yes Chemosis 0. No 1. Yes Conjunctival injection 0. No 1. Yes Exophthalmos 0. No 1. Yes Hertel - base right left Eye muscle dysfunction 0. No 1. Yes Corneal ulcers 0. No 1. Yes Sum: Ophthalmopathy is present if the patient has one sign or more.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations.
   Lantz M, Calissendorff J, Träisk F, Tallstedt L, et al · · 2016 · cited 9× · PMID 27099839 · DOI 10.1159/000443373