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

This study is currently recruiting participants.
Verified September 2012 by Region Skane
Sponsor:
Information provided by (Responsible Party):
Mikael Lantz, Region Skane
ClinicalTrials.gov Identifier:
NCT01458600
First received: October 19, 2011
Last updated: September 6, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Graves´ Disease
 Drug: Diclofenac
Drug: Methimazole
Drug: L-thyroxin
Drug: Propranolol
Drug: Metoprolol
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Adjuvant Treatment of Graves´ Ophthalmopathy With NSAID (aGO Study)

Resource links provided by NLM:

MedlinePlus related topics: Eye Diseases
U.S. FDA Resources

Further study details as provided by Region Skane:

Primary Outcome Measures:
  • The frequency of ophthalmopathy after 24 months as judged by the following clinical signs [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Activity of ophthalmopathy as judged by clinical activity score (CAS) [ Time Frame: 0,12,24 months ] [ Designated as safety issue: No ]

    Spontaneous retrobulbar pain 0. No 1. Yes Painfull eye-movements 0. No 1. Yes Eye-lid erythema 0. No 1. Yes Conjunctival injection 0. No 1. Yes Chemosis 0. No 1. Yes Swollen caruncula 0. No 1. Yes Eye-lid edema or swolleness 0. No 1. Yes

    Sum:


  • The time from thyrotoxicosis to ophthalmopathy. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • The frequency of corticosteroid requiring ophthalmopathy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Criteria for start of steroid treatment are: 1. Risk of corneal ulcers with or without exophthalmos 2. Double vision within 30 degrees 3. Optic nerve dysfunction.


Estimated Enrollment: 150
Study Start Date: September 2006
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: diclofenac
12 months treatment with diclofenac 50 mg 1x2 in addition to regular treatment for thyrotoxicosis.
 Drug: Diclofenac
T Diclofenac 50 mg twice daily for 12 months
Other Name: T Diclofenac T 50 mg Ratiopharm
Drug: Methimazole
T Methimazole 5 mg 3x2 for 18 months
Other Name: Thacapzol (Recip)
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
Other Name: Euthyrox (Merck)
Drug: Propranolol
T Propronalol 40mg 1x1-3 during during 1-3 weeks until the patient has responded to thyrostatics
Other Name: Inderal (AstraZeneca)
Drug: Metoprolol
T Metoprolol 50 mg 1x3 for 1-3 weeks until the patient has responded to thyrostatics
Other Name: Seloken (AstraZeneca)
without diclofenac
12 months treatment without diclofenac in addition to regular treatment for thyrotoxicosis.
 Drug: Methimazole
T Methimazole 5 mg 3x2 for 18 months
Other Name: Thacapzol (Recip)
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
Other Name: Euthyrox (Merck)
Drug: Propranolol
T Propronalol 40mg 1x1-3 during during 1-3 weeks until the patient has responded to thyrostatics
Other Name: Inderal (AstraZeneca)
Drug: Metoprolol
T Metoprolol 50 mg 1x3 for 1-3 weeks until the patient has responded to thyrostatics
Other Name: Seloken (AstraZeneca)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01458600

Contacts
Contact: Mikael Lantz, MD +46 708 202315 Mikael.Lantz@med.lu.se

Locations
Sweden
Departmenty of Endocrinology, Skane University Hospital Recruiting
Malmö, Sweden
Contact: Mikael Lantz, MD            
Principal Investigator: Mikael Lantz, MD            
Department of Endocrinology, Karolinska Hospital Recruiting
Stockholm, Sweden
Contact: Jan Calissendorff, MD     +46 70 573 69 71        
Principal Investigator: Jan Calissendorff, MD            
Department of Internal Medicine, section of Endocrinology, Sodersjukhuset Not yet recruiting
Stockholm, Sweden
Contact: Ove Törring, MD         ove.torring@sodersjukhuset.se    
Principal Investigator: Ove Törring, MD            
Sponsors and Collaborators
Mikael Lantz
Investigators
Study Director: Mikael Lantz, MD Department of Endocrinology, Skane University Hospital, Malmö, Sweden
Principal Investigator: Jan Calissendorff, MD Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden
Principal Investigator: Ove Törring, MD Department of Internal Medicine, section of Endocrinology, Sodersjukhuset, Stockholm
  More Information

No publications provided

Responsible Party: Mikael Lantz, Associate Professor, Region Skane
ClinicalTrials.gov Identifier: NCT01458600     History of Changes
Other Study ID Numbers: 2005 02 23, 2005-000832-26
Study First Received: October 19, 2011
Last Updated: September 6, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by Region Skane:
ophthalmopathy
prevention
diclofenac

Additional relevant MeSH terms:
Graves Disease
Graves Ophthalmopathy
Eye Diseases
Exophthalmos
Orbital Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Eye Diseases, Hereditary
Anti-Inflammatory Agents, Non-Steroidal
Diclofenac
Metoprolol
 Propranolol
Metoprolol succinate
Methimazole
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents

ClinicalTrials.gov processed this record on May 21, 2013