Graves OphthalmopathyRETROSIRGONCT05345119
Sirolimus in Graves' Orbitopathy
An observational study of Graves Ophthalmopathy, run by University of Pisa at 1 site in Italy.
Trial summary
Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graves Ophthalmopathy
- What is being tested?
- Sirolimus and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 15 Jan 2020to 15 Jun 2021
- Phase
- Observational
- 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
Study population: Consecutive patients with moderate-to-severe, active Graves' orbitopathy treated with either sirolimus of methyprednisolone as a second-line treatment after a previous course of methyprednisolone, over 18 consecutive months
Who may be able to join
- Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
- Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
- Male and female patients of age: 18-75 years
Who cannot join
- Optic neuropathy
- Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment
- Mental illness that prevents patients from comprehensive, written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Observational, Retrospective, Single-center, Clinical Study to Evaluate the Efficacy of Sirolimus (Rapamycin) in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO)
Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug.
The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO.
The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.
Read the detailed description
Study Design: observational
Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared.
Study Timeline
Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)
- Conditions
- Graves Ophthalmopathy
- Being tested
- Sirolimus, Methylprednisolone
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
2 mg orally on the first day followed by 0.5 mg per day for 12 weeks
500 mg/weekly (6 weeks) intravenously, 250 mg/weekly (6 weeks) (cumulative dose 4.5 g).
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Treatment with sirolimus for 12 weeks, given as a second-line treatment Receives: Drug: Sirolimus | |
| Methylprednisolone | Treatment with methylprednisolone for 12 weeks, given as a second-line treatment Receives: Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
GO overall response
Percentage of subjects with at least two of the following compared to baseline: a) Improvement in clinical activity score (CAS) by at least 1 point ; b) Improvement in exophthalmos by at least 2 mm; c) Improvement in lid aperture by at least 2 mm; d) Improvement in eye muscle ductions ≥8 degrees; e) Improvement of visual acuity by at least 0.2/1, without worsening of any of these parameters in the contralateral eye if applicable.
Measured: 24 weeks
Secondary outcomes (6)
Change in exophthalmos
Percentage of subjects with a reduction greater than or equal to 2 mm compared with the baseline evaluation in the study eye, without worsening in the contralateral eye
Measured: 24 weeks
Change in the clinical activity score (CAS)
Percentage of subjects with a reduction of CAS by at least two points in the study eye, without worsening in the contralateral eye
Measured: 24 weeks
Change in quality of life
Comparison of the quality of life scores between the two groups, determined with a questionnaire specific for GO (GO-QoL)
Measured: 24 weeks
Change in eye ductions
Percentage of subjects with an increase in eye ductions at least 8 degrees
Measured: 24 weeks
Change in eyelid aperture
Percentage of subjects with a reduction greater than or equal to 2 mm
Measured: 24 weeks
Change in diplopia
Percentage with an improvement in diplopia
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start15 Jan 2020
- Primary completion15 Jun 2021
- Study completion15 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves OphthalmopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marinò Michele, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05345119
- Sponsor's protocol ID
- RETROSIRGO
- Acronym
- RETROSIRGO
- Status last verified
- Apr 2022
- First submitted
- 19 Apr 2022
- Last updated
- 25 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational, Retrospective, Single-center, Clinical Study to Evaluate the Efficacy of Sirolimus (Rapamycin) in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO)
- ClinicalTrials.gov ID
- NCT05345119
- Acronym / sponsor ID
- RETROSIRGO / RETROSIRGO
- Conditions
- Graves Ophthalmopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 15 Jun 2021 (actual)
- Study completion
- 15 Jun 2021 (actual)
- First posted
- 25 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug.
The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO.
The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.
Detailed description
Study Design: observational
Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared.
Study Timeline
Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | – | Drug: SirolimusTreatment with sirolimus for 12 weeks, given as a second-line treatment |
| Methylprednisolone | – | Drug: MethylprednisoloneTreatment with methylprednisolone for 12 weeks, given as a second-line treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients with moderate-to-severe, active Graves' orbitopathy treated with either sirolimus of methyprednisolone as a second-line treatment after a previous course of methyprednisolone, over 18 consecutive months
Key inclusion criteria (5 listed)
- Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
- Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
- Male and female patients of age: 18-75 years
Key exclusion criteria (3 listed)
- Optic neuropathy
- Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment
- Mental illness that prevents patients from comprehensive, written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sirolimus2 mg orally on the first day followed by 0.5 mg per day for 12 weeks | Drug | Sirolimus |
| Methylprednisolone500 mg/weekly (6 weeks) intravenously, 250 mg/weekly (6 weeks) (cumulative dose 4.5 g). | Drug | Methylprednisolone |
Primary outcome
GO overall response
Time frame: 24 weeks
Percentage of subjects with at least two of the following compared to baseline: a) Improvement in clinical activity score (CAS) by at least 1 point ; b) Improvement in exophthalmos by at least 2 mm; c) Improvement in lid aperture by at least 2 mm; d) Improvement in eye muscle ductions ≥8 degrees; e) Improvement of visual acuity by at least 0.2/1, without worsening of any of these parameters in the contralateral eye if applicable.
6 secondary outcomes
Change in exophthalmos
Time frame: 24 weeks
Change in the clinical activity score (CAS)
Time frame: 24 weeks
Change in quality of life
Time frame: 24 weeks
Change in eye ductions
Time frame: 24 weeks
Change in eyelid aperture
Time frame: 24 weeks
Change in diplopia
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Individual participant dataSharing planned: Undecided
Related trials for Graves Ophthalmopathy
RecruitingPhase 2
Evaluation of YB-101 for Safety, Tolerability, Pharmacokinetics, and Efficacy in Graves' Disease
Graves' Disease
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease
RecruitingPhase 1
NEXUS Study: A Study to Test Single and Multiple Doses of MER511 Given to Adults With Graves' Disease
Graves Disease
RecruitingPhase 2
A Study to Investigate the Efficacy and Safety of Rilzabrutinib in Adult Participants With Graves' Disease
Graves' Disease
Not yet recruitingPhase 2/3
An Open-Label Study to Determine if BHV-1300 is Safe in Adults With Graves' Disease
Graves' Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Graves Ophthalmopathy, 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 5 inclusion and 3 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 25 Apr 2022. 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.
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?
GO overall response (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Apr 2022.