Effects of Atorvastatin in Graves' Orbitopathy (GO)

NCT ID: NCT03110848

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2021-04-30

Brief 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 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.

Conditions

Thyroid Associated Ophthalmopathy; Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Statins

Atorvastatin 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.

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

Atorvastatin 20 mg daily

Methylprednisolone

Intervention Type: DRUG

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.

No statins

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.

Group Type: ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type: DRUG

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.

Interventions

Atorvastatin

Atorvastatin 20 mg daily

Intervention Type: DRUG

Methylprednisolone

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.

Intervention Type: DRUG

Other Intervention Names

Statins; Intravenous glucocorticoids

Eligibility Criteria

Exclusion Criteria

1. lack of informed consent

2. Absence of Graves' hyperthyroidism (present or past)

3. Inactive GO

4. Optic neuropathy

5. Corticosteroids or immunosuppressive treatment for GO in the last 3 months.

6. Previous surgical treatment for GO

7. Contraindications to GC

8. Pregnancy, breast-feeding women

9. Acute or chronic liver disease

10. Hypersensitivity to atorvastatin or other statins, or hypersensitivity or intolerance to the medication excipients such as lactose.

11. Medications interfering/interacting with statins (CYP3A4 inhibitors or inductors)

12. Relevant Malignancy

13. Corticosteroids or other immunosuppressive agents within last 3 months

14. Recent (≤1 year) history of alcoholism or drug abuse

15. Clinical ASCVD (AthroSclerotic CardioVascular Disease)

16. 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)

17. Severe familial hyperlipemia

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Marinò Michele

Ricercatore (Assistant Professor)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ospedale Cisanello-Endocrinology I and II

Pisa, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 34592164 (View on PubMed)

Other Identifiers

STAGO

Identifier Type: -

Identifier Source: org_study_id