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Thyroid Associated OphthalmopathyPhase 2STAGONCT03110848

Effects of Atorvastatin in Graves' Orbitopathy (GO)

A Phase 2 study testing Atorvastatin and Methylprednisolone in people with Thyroid Associated Ophthalmopathy and Hypercholesterolemia, run by University of Pisa at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Graves' orbitopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease (GD), being observed in ~25% of patients. Besides genetic and demographical variables, risk factors associated with the development of GO in GD patients are known to be inadequate control of hyperthyroidism, radioiodine… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Atorvastatin and Methylprednisolone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
1 siteItaly
Study dates
1 Jun 2020to 30 Apr 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • lack of informed consent
  • Absence of Graves' hyperthyroidism (present or past)
  • Inactive GO
  • Optic neuropathy
  • Corticosteroids or immunosuppressive treatment for GO in the last 3 months.
  • Previous surgical treatment for GO
Show all 17Show fewer
  • Contraindications to GC
  • Pregnancy, breast-feeding women
  • Acute or chronic liver disease
  • Hypersensitivity to atorvastatin or other statins, or hypersensitivity or intolerance to the medication excipients such as lactose.
  • Medications interfering/interacting with statins (CYP3A4 inhibitors or inductors)
  • Relevant Malignancy
  • Corticosteroids or other immunosuppressive agents within last 3 months
  • Recent (≤1 year) history of alcoholism or drug abuse
  • Clinical ASCVD (AthroSclerotic CardioVascular Disease)
  • LDL-cholesterol levels ≥190 mg/dl or presence of more than one associated cardiovascular risk factor (diabetes, high blood pressure, smoking, familial history of acute cardiovascular events, obesity)
  • Severe familial hyperlipemia

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale Cisanello-Endocrinology I and II

    Pisa, 56124

Other trials in Italy

About this study

Official title: A Phase II, Open-labeled, Ophthalmological External Investigator-blinded, Single-center, Randomized, Superiority, Non Profit, Pilot Clinical Trial to Evaluate the Effects of Atorvastatin on Graves' Orbitopathy (GO) in Hypercholesterolemic Patients With Moderate-to-severe and Active GO Subjected to Intravenous Glucocorticoid Therapy: the STAGO Study

Graves' orbitopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease (GD), being observed in ~25% of patients. Besides genetic and demographical variables, risk factors associated with the development of GO in GD patients are known to be inadequate control of hyperthyroidism, radioiodine treatment, and smoking. In a large retrospective study conducted in more than 8,000 individuals with GD it was observed that treatment with 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, better known as statins, is associated with a ~40% reduced risk of developing GO in GD patients. The findings were interpreted as the consequence of the anti-inflammatory action of statins, being GO notoriously an autoimmune, inflammatory conditions.

Statins are widely used for the treatment of hypercholesterolemia, for which they are quite effective. The possibility that their "protective" effect in terms of GO development in GD patients, as observed by Stein et al., was simply due to their hypolipemic actions was not considered. To evaluate the possibility that the findings reflected lowering of cholesterol rather than a direct anti-inflammatory effect of statins a prospective, observational study to assess the association between GO and high cholesterol levels and/or the relationship between the degree and/or activity of GO and hypercholesterolemia is ongoing. Preliminary findings suggest that GO is more severe and active in patients with high cholesterol levels. On the basis of these observations, the present randomized clinical trial was designed to be performed in hypercholesterolemic patients with GD and moderate-to-severe and active GO, aimed at investigating if lowering of cholesterol levels with statins is associated with a better outcome of GO.

Medical subject headings
Graves Ophthalmopathy, Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtorvastatinDrug

    Also called Statins

    Atorvastatin 20 mg daily

  • MethylprednisoloneDrug

    Also called Intravenous glucocorticoids

    500 mg of methylprednisolone weekly for 6 weeks, followed by 250 mg weekly for another 6 weeks, for a total dose of 4.5 mg.

Study groups in NCT03110848
Study groupRoleWhat they receive
StatinsExperimentalAtorvastatin 20 mg daily associated with intravenous glucocorticoids, namely 500 mg of methylprednisolone weekly for 6 weeks, followed by 250 mg weekly for another 6 weeks, for a total dose of 4.5 mg.
Receives: Drug: Atorvastatin; Drug: Methylprednisolone
No statinsActive comparatorIntravenous glucocorticoids, namely 500 mg of methylprednisolone weekly for 6 weeks, followed by 250 mg weekly for another 6 weeks, for a total dose of 4.5 mg.
Receives: Drug: Methylprednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall GO outcome determined using a composite evaluation

    Overall GO outcome determined using a composite evaluation.

    A composite evaluation of GO was described previously.

    Possible outcomes are: improvement, worsening, no change, resulting in 3 categorical values

    Improvement: amelioration of two parameters in at least one eye, without deterioration of any parameters in both eyes:

    Deterioration: worsening in two parameters in at least one eye:

    All other cases are "no change"

    Parameters are:

    Eyelid swelling (improvement/worsening according to EUGOGO Atlas evaluation) Lid aperture in mm (significant variation: 2 or more mm) Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant change: at least 2 points) Exophthalmos in mm (significant variation 2 or more mm) Eye muscle involvement - diplopia score (Gorman score) (significant variation: disappearance or change in the degree, or improvement of ≥12 degrees in motility)

    Measured: 6 months

Secondary outcomes (6)

  1. Overall GO outcome determined using a composite evaluation

    Overall GO outcome determined using a composite evaluation.

    A composite evaluation of GO was described previously.

    Possible outcomes are: improvement, worsening, no change, resulting in 3 categorical values

    Improvement: amelioration of two parameters in at least one eye, without deterioration of any parameters in both eyes:

    Deterioration: worsening in two parameters in at least one eye:

    All other cases are "no change"

    Parameters are:

    Eyelid swelling (improvement/worsening according to EUGOGO Atlas evaluation) Lid aperture in mm (significant variation: 2 or more mm) Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant change: at least 2 points) Exophthalmos in mm (significant variation 2 or more mm) Eye muscle involvement - diplopia score (Gorman score) (significant variation: disappearance or change in the degree, or improvement of ≥12 degrees in motility)

    Measured: 3 months

  2. Comparison of a disease specific quality of life questionnaire (GO-QoL)

    A GO-specific quality of life questionnaire (GO-QoL) comprises 16 items, 8 concerning appearance and 8 concerning function. The combination of the various parameters gives a final numeric value which will be compared between the two groups

    Measured: 6 months

  3. Comparison of a disease specific quality of life questionnaire (GO-QoL)

    A GO-specific quality of life questionnaire (GO-QoL) comprises 16 items, 8 concerning appearance and 8 concerning function. The combination of the various parameters gives a final numeric value which will be compared between the two groups

    Measured: 3 months

  4. GO relapse

    Worsening in comparison with the 3-month evaluation

    Measured: 6 months

  5. Requirement for additional treatments

    Additional intravenous glucocorticoids, radiotherapy, orbital decompression, immunosuppressive treatments of any kind

    Measured: 3 months

  6. Requirement for additional treatments

    Additional intravenous glucocorticoids, radiotherapy, orbital decompression, immunosuppressive treatments of any kind

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2017
  2. Study start1 Jun 2020
  3. Primary completion30 Apr 2021
  4. Study completion30 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03110848
Sponsor's protocol ID
STAGO
Acronym
STAGO
Status last verified
Aug 2021
First submitted
23 Mar 2017
Last updated
13 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lanzolla G, Sabini E, Leo M, Menconi F, Rocchi R, Sframeli A, Piaggi P, Nardi M, Marcocci C, Marino M. Statins for Graves' orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial. Lancet Diabetes Endocrinol. 2021 Nov;9(11):733-742. doi: 10.1016/S2213-8587(21)00238-2. Epub 2021 Sep 27.

    PubMed 34592164

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atorvastatin and Methylprednisolone in people with Thyroid Associated Ophthalmopathy and Hypercholesterolemia, run by University of Pisa at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall GO outcome determined using a composite evaluation (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03110848, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2021.

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