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

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.

Conditions

• Graves´ Disease

Interventions

DRUG

Diclofenac

T Diclofenac 50 mg twice daily for 12 months

DRUG

Methimazole

T Methimazole 5 mg 3x2 for 18 months

DRUG

L-thyroxin

L-thyroxin approximately 100 to 200 micrograms/day. The dose is adjusted to reach euthyroidism during concomitant treatment with methimazole for 18 months

DRUG

Propranolol

T Propronalol 40mg 1x1-3 during during 1-3 weeks until the patient has responded to thyrostatics

DRUG

Metoprolol

T Metoprolol 50 mg 1x3 for 1-3 weeks until the patient has responded to thyrostatics

Sponsors & Collaborators

• Mikael Lantz

  lead OTHER

Principal Investigators

• Mikael Lantz, MD · Department of Endocrinology, Skane University Hospital, Malmö, Sweden

• Jan Calissendorff, MD · Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden

• Ove Törring, MD · Department of Internal Medicine, section of Endocrinology, Sodersjukhuset, Stockholm

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-09-30

Primary Completion

2016-02-29

Completion

2016-02-29

Countries

• Sweden

Study Locations