NCT03110848: STAGO

Effects of Atorvastatin in Graves' Orbitopathy (GO)

Completed Phase 2 Last updated 13 August 2021

What this trial tests

Phase 2 trial testing Atorvastatin in Thyroid Associated Ophthalmopathy in 88 participants. Completed in 30 April 2021.

Timeline

1 June 2020

Primary endpoint
30 April 2021

30 April 2021

Quick facts

Lead sponsor	University of Pisa
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	88
Start date	1 June 2020
Primary completion	30 April 2021
Estimated completion	30 April 2021
Sites	1 location across Italy

Drugs / interventions tested

• Atorvastatin (atorvastatin) — full drug profile →
• Methylprednisolone (methylprednisolone) — full drug profile →

Conditions studied

• Thyroid Associated Ophthalmopathy — all drugs for Thyroid Associated Ophthalmopathy →
• Hypercholesterolemia — all drugs for Hypercholesterolemia →

Sponsor

University of Pisa

Who can join

Adults 18 to 75, any sex, with Thyroid Associated Ophthalmopathy or Hypercholesterolemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Multifunctional nanoparticle-mediated combining therapy for human diseases.
   Li X, Peng X, Zoulikha M, Boafo GF, et al · · 2024 · cited 207× · PMID 38161204 · DOI 10.1038/s41392-023-01668-1
2. Statins for Graves' orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial.
   Lanzolla G, Sabini E, Leo M, Menconi F, et al · · 2021 · cited 72× · PMID 34592164 · DOI 10.1016/s2213-8587(21)00238-2
3. Thyroid eye disease: From pathogenesis to targeted therapies.
   Yoon JS, Kikkawa DO. · · 2022 · cited 19× · PMID 35399971 · DOI 10.4103/tjo.tjo_51_21
4. Emerging therapies in the medical management of thyroid eye disease.
   Kamboj A, Harrison AR, Mokhtarzadeh A. · · 2023 · cited 4× · PMID 38983101 · DOI 10.3389/fopht.2023.1295902
5. Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.
   Cui Y, Feng Z, Zhao Q, Dai H, et al · · 2025 · PMID 41280910 · DOI 10.3389/fimmu.2025.1713148