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

NCT01458600 | Completed Phase 4 DMC

• 2 other identifiers: 2005 02 232005-000832-26
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 3

Brief 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. 1.To study the frequency of clinical ophthalmopathy in Graves´ disease after 12 months treatment with or without diclofenac.
2. 2.To study the frequency of progress of clinical signs and symptoms in ophthalmopathy after 12 months treatment with or without diclofenac.
3. 3.To study the frequency of optic neuropathy in clinical ophthalmopathy after 12 months treatment with or without diclofenac.

Conditions

Graves´ Disease

Keywords

ophthalmopathy; prevention; diclofenac

Outcome Measures

Primary Outcomes (1)

• The frequency of ophthalmopathy after 24 months as judged by the following clinical signs

  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.

  24 months

Secondary Outcomes (3)

• Activity of ophthalmopathy as judged by clinical activity score (CAS)

  0,12,24 months

• The time from thyrotoxicosis to ophthalmopathy.

  24 months

• The frequency of corticosteroid requiring ophthalmopathy

  24 months

Study Arms (2)

diclofenac

ACTIVE COMPARATOR

12 months treatment with diclofenac 50 mg 1x2 in addition to regular treatment for thyrotoxicosis.

Drug: Diclofenac; Drug: Methimazole; Drug: L-thyroxin; Drug: Propranolol; Drug: Metoprolol

without diclofenac

OTHER

12 months treatment without diclofenac in addition to regular treatment for thyrotoxicosis.

Drug: Methimazole; Drug: L-thyroxin; Drug: Propranolol; Drug: Metoprolol

Interventions

Diclofenac DRUG

T Diclofenac 50 mg twice daily for 12 months

Also known as: T Diclofenac T 50 mg Ratiopharm

diclofenac

Methimazole DRUG

T Methimazole 5 mg 3x2 for 18 months

Also known as: Thacapzol (Recip)

diclofenac; without diclofenac

L-thyroxin DRUG

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

Also known as: Euthyrox (Merck)

diclofenac; without diclofenac

Propranolol DRUG

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

Also known as: Inderal (AstraZeneca)

diclofenac; without diclofenac

Metoprolol DRUG

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

Also known as: Seloken (AstraZeneca)

diclofenac; without diclofenac

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Graves thyrotoxicosis ( with clinical symptoms)
• Age 18 - 75 year
• TSH = 0.2 or \< 0.2 and increased fT4 and/or fT3
• Signed informed consent

You may not qualify if:

• Pregnancy or breastfeeding, women in childbearing age should use non- barrier contraceptives
• Previous treatment of thyroid disease
• Thyrostatics before radioiodine treatment
• Hypersensitivity to NSAID or ASA
• Congestive heartfailure
• Impaired renal function defined as p-creatinine \> 100 mmol/L
• ASAT or ALAT \> 2.5 times the upper limit
• Alcoholism
• Coagulopathy including warfarin treatment
• Thrombocytopenia
• Previous or active gastric ulcera
• Inflammatory bowel disease

Sponsors & Collaborators

• Mikael Lantz: lead

Study Sites (3)

Departmenty of Endocrinology, Skane University Hospital

Malmo, Sweden

Location

Department of Endocrinology, Karolinska Hospital

Stockholm, Sweden

Location

Department of Internal Medicine, section of Endocrinology, Sodersjukhuset

Stockholm, Sweden

Location

MeSH Terms

Conditions

Graves Disease; Eye Diseases

Interventions

Diclofenac; Methimazole; Thyroxine; Propranolol; Metoprolol

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Mikael Lantz, MD

  Department of Endocrinology, Skane University Hospital, Malmö, Sweden

  STUDY DIRECTOR

• Jan Calissendorff, MD

  Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

• Ove Törring, MD

  Department of Internal Medicine, section of Endocrinology, Sodersjukhuset, Stockholm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 19, 2011
• First Posted: October 25, 2011
• Study Start: September 1, 2006
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 24, 2016

Record last verified: 2016-02

Locations

SE (3)