Thyroid Eye DiseasePhase 4HALRNCT01738243
Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease
A Phase 4 study testing Hyaluronic Acid Gel injection and Saline injection in people with Thyroid Eye Disease, run by University of California, Los Angeles at 2 sites in United States.
Trial summary
Thyroid eye disease (TED) is an autoimmune disease that affects the eye area. The disease presents with a variety of physical findings, including bulging of the eyes (proptosis), upper and lower eyelid retraction, and swelling/inflammation of the eye itself. The disease passes through two phases: active and inactive. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Thyroid Eye Disease
- What is being tested?
- Hyaluronic Acid Gel injection and Saline injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2013to Sep 2021
- Phase
- Phase 4
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active stage TO as determined by symptom onset of under 9 months.
- Upper eyelid retraction of 1mm or greater in one or both eyes.
- Complaints of either significant ocular symptoms (despite appropriate use of ocular lubricants), or cosmetic deformity associated with the eyelid retraction.
Who cannot join
- Age less than 21 years: due to lack of data on safety for HAG fillers in pediatric population
- Age over 65 years of age: as HAG filler effect may be different in this population
- Are pregnant or nursing: as there is little safety data on potential teratogenicity of HAG fillers
- Have a demonstrated allergy to HAG fillers or lidocaine
- Have a current infection, skin sore, pimple, rash, hive or cyst over the injection site: to avoid worsening the infection or transmitting it
- Have a bleeding disorder or currently taking blood thinning medications such as Coumadin, heparin or acetylsalicylic acid on a daily basis.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Jules Stein Eye Institute
Los Angeles, California, 90095
The Jules Stein Eye Institute at UCLA
Los Angeles, California, 90095
About this study
Official title: Phase IV Study of Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease
Thyroid eye disease (TED) is an autoimmune disease that affects the eye area. The disease presents with a variety of physical findings, including bulging of the eyes (proptosis), upper and lower eyelid retraction, and swelling/inflammation of the eye itself.
The disease passes through two phases: active and inactive. The active phase lasts between 18 and 24 months. During this phase, TED signs and symptoms generally worsen and then often improve. The inactive phase follows, during which the signs and symptoms of TED cease to improve and usually stabilize.
Read more
Lid retraction is a cardinal sign of TED. In addition to potentially causing cornea damage due to improper lid closure, lid retraction is also very troublesome for patients due to its cosmetic appearance. The precise pathophysiology of lid retraction is poorly understood, but a leading hypothesis is that it occurs due to scarring and fibrosis in the muscles that lift the eyelid.
Currently, the definitive treatment for lid retraction is surgery, which can be used to lengthen the lid itself or remove inflamed tissue from behind the eye, thus causing the eye to bulge less. In cases when patients first present to their physician with corneal ulceration or compression of the optic nerve, surgery may be performed immediately. However, in most instances, surgical procedures are delayed until the active stage of the disease has passed. Thus, most patients must endure the cosmetic and irritant symptoms of TED for up to two years.
Hyaluronic Acid Gels (HAG) have been FDA approved for the treatment of facial rhytids (wrinkles). They are injected under the skin and work by increasing volume. Recently, some smaller retrospective research studies have shown that HAG is also effective in correcting upper and lower eyelid retraction in TED. Hence, HAG may be for patients with active stage TED. It is also thought that if employed early in active phase disease, HAG may also help to decrease the severity of associated symptoms and reduce the need for surgery.
The purpose of the current investigation is to define the clinical utility of HAG correction of upper eyelid in active TED in terms of anatomic (lid position), quantitative (corneal dry eye signs) and qualitative effects (symptom severity and thyroid related quality of life).
- Conditions
- Thyroid Eye Disease
- Being tested
- Hyaluronic Acid Gel injection, Saline injection
- Keywords
- Thyroid, Thyroid Eye Disease, Thyroid Orbitopathy, Eyelid Retraction, Upper Eyelid Retraction
- Medical subject headings
- Graves Ophthalmopathy, Thyroid Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic Acid Gel injectionDrug
Also called Restylane, Belotero
The conjunctiva is anesthetized with Proparacaine Hydrochloride Ophthalmic Solution, 0.5%. The upper eyelid is everted and the conjunctiva just superior to the upper tarsal edge is exposed. Using a 30-gauge needle, a single bolus of Hyaluronic Acid Gel is placed centrally in the subconjunctival levator-Muller plane. Small volumes (0.1 to 0.2 ml) of Hyaluronic Acid Gel are injected with the end point being adequate lowering with improved symmetry.
Saline injectionDrug
Also called Normal saline
The conjunctiva is anesthetized with Proparacaine Hydrochloride Ophthalmic Solution, 0.5%. The upper eyelid is everted and the conjunctiva just superior to the upper tarsal edge is exposed. Using a 30-gauge needle, a single bolus of saline is placed centrally in the subconjunctival levator-Muller plane. Small volumes (0.1 to 0.2 ml) of saline are injected with the end point being adequate lowering with improved symmetry.
| Study group | Role | What they receive |
|---|---|---|
| Unilateral Upper Eyelid Retraction | Experimental | This arm will consist of participants with unilateral upper eye lid retraction secondary to thyroid eye disease (TED).
Patients enrolled will be randomized 1:1 to Hyaluronic Acid Gel Injection or Saline injection Receives: Drug: Hyaluronic Acid Gel injection; Drug: Saline injection |
| Bilateral Upper Eyelid Retraction | Experimental | This arm will consist of participants with bilateral upper eye lid retraction secondary to thyroid eye disease (TED).
Patients enrolled will be randomized 1:1 to Hyaluronic Acid Gel injection or Saline injection Receives: Drug: Hyaluronic Acid Gel injection; Drug: Saline injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Upper eyelid scleral show and marginal reflex distance 1 in mm
Physicians will measure the amount of lid retraction (upper eyelid scleral show, marginal reflex distance 1) present in study participants 6 weeks following injection of hyaluronic acid gel vs. saline.
Measured: 6 weeks after injection
Secondary outcomes (3)
Dry Eye
We will measure severity of dry eye signs using the Oxford staining scale and the Ocular surface disease index
Measured: 6 weeks post injection.
Quality of life
The Graves Orbitopathy Quality of Life (GO-QOL) survey will be given to subjects at entry and at 6 weeks.
Measured: 6 weeks
Complications
Complications including null effect, ecchymosis, retrobulbar hemorrhage, cranial nerve injury and extraocular muscle dysfunction will be monitored and reported
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2012 (estimated)
- Study startDec 2013
- Primary completionSep 2021
- Study completionSep 2021
Why it stopped: recruitment challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Eye DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Rootman, University of California, Los Angeles
- Investigators
- Daniel Rootman, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01738243
- Sponsor's protocol ID
- PRE#12-003174
- Acronym
- HALR
- Status last verified
- Sep 2021
- First submitted
- 6 Oct 2012
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Study of Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease
- ClinicalTrials.gov ID
- NCT01738243
- Acronym / sponsor ID
- HALR / PRE#12-003174
- Conditions
- Thyroid Eye Disease
- Keywords
- Thyroid, Thyroid Eye Disease, Thyroid Orbitopathy, Eyelid Retraction, Upper Eyelid Retraction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment challenges
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Sep 2021 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 30 Nov 2012 (estimated)
- 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.
Thyroid eye disease (TED) is an autoimmune disease that affects the eye area. The disease presents with a variety of physical findings, including bulging of the eyes (proptosis), upper and lower eyelid retraction, and swelling/inflammation of the eye itself.
The disease passes through two phases: active and inactive. The active phase lasts between 18 and 24 months. During this phase, TED signs and symptoms generally worsen and then often improve. The inactive phase follows, during which the signs and symptoms of TED cease to improve and usually stabilize.
Lid retraction is a cardinal sign of TED. In addition to potentially causing cornea damage due to improper lid closure, lid retraction is also very troublesome for patients due to its cosmetic appearance. The precise pathophysiology of lid retraction is poorly understood, but a leading hypothesis is that it occurs due to scarring and fibrosis in the muscles that lift the eyelid.
Currently, the definitive treatment for lid retraction is surgery, which can be used to lengthen the lid itself or remove inflamed tissue from behind the eye, thus causing the eye to bulge less. In cases when patients first present to their physician with corneal ulceration or compression of the optic nerve, surgery may be performed immediately. However, in most instances, surgical procedures are delayed until the active stage of the disease has passed. Thus, most patients must endure the cosmetic and irritant symptoms of TED for up to two years.
Hyaluronic Acid Gels (HAG) have been FDA approved for the treatment of facial rhytids (wrinkles). They are injected under the skin and work by increasing volume. Recently, some smaller retrospective research studies have shown that HAG is also effective in correcting upper and lower eyelid retraction in TED. Hence, HAG may be for patients with active stage TED. It is also thought that if employed early in active phase disease, HAG may also help to decrease the severity of associated symptoms and reduce the need for surgery.
The purpose of the current investigation is to define the clinical utility of HAG correction of upper eyelid in active TED in terms of anatomic (lid position), quantitative (corneal dry eye signs) and qualitative effects (symptom severity and thyroid related quality of life).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Unilateral Upper Eyelid Retraction | Experimental | Drug: Hyaluronic Acid Gel injection, Drug: Saline injectionThis arm will consist of participants with unilateral upper eye lid retraction secondary to thyroid eye disease (TED). Patients enrolled will be randomized 1:1 to Hyaluronic Acid Gel Injection or Saline injection |
| Bilateral Upper Eyelid Retraction | Experimental | Drug: Hyaluronic Acid Gel injection, Drug: Saline injectionThis arm will consist of participants with bilateral upper eye lid retraction secondary to thyroid eye disease (TED). Patients enrolled will be randomized 1:1 to Hyaluronic Acid Gel injection or Saline injection |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Active stage TO as determined by symptom onset of under 9 months.
- Upper eyelid retraction of 1mm or greater in one or both eyes.
- Complaints of either significant ocular symptoms (despite appropriate use of ocular lubricants), or cosmetic deformity associated with the eyelid retraction.
Key exclusion criteria (6 listed)
- Age less than 21 years: due to lack of data on safety for HAG fillers in pediatric population
- Age over 65 years of age: as HAG filler effect may be different in this population
- Are pregnant or nursing: as there is little safety data on potential teratogenicity of HAG fillers
- Have a demonstrated allergy to HAG fillers or lidocaine
- Have a current infection, skin sore, pimple, rash, hive or cyst over the injection site: to avoid worsening the infection or transmitting it
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 |
|---|---|---|
| Hyaluronic Acid Gel injectionAlso: Restylane, BeloteroThe conjunctiva is anesthetized with Proparacaine Hydrochloride Ophthalmic Solution, 0.5%. The upper eyelid is everted and the conjunctiva just superior to the upper tarsal edge is exposed. Using a 30-gauge needle, a single bolus of Hyaluronic Acid Gel is placed centrally in the subconjunctival levator-Muller plane. Small volumes (0.1 to 0.2 ml) of Hyaluronic Acid Gel are injected with the end point being adequate lowering with improved symmetry. | Drug | Bilateral Upper Eyelid Retraction, Unilateral Upper Eyelid Retraction |
| Saline injectionAlso: Normal salineThe conjunctiva is anesthetized with Proparacaine Hydrochloride Ophthalmic Solution, 0.5%. The upper eyelid is everted and the conjunctiva just superior to the upper tarsal edge is exposed. Using a 30-gauge needle, a single bolus of saline is placed centrally in the subconjunctival levator-Muller plane. Small volumes (0.1 to 0.2 ml) of saline are injected with the end point being adequate lowering with improved symmetry. | Drug | Bilateral Upper Eyelid Retraction, Unilateral Upper Eyelid Retraction |
Primary outcome
Upper eyelid scleral show and marginal reflex distance 1 in mm
Time frame: 6 weeks after injection
Physicians will measure the amount of lid retraction (upper eyelid scleral show, marginal reflex distance 1) present in study participants 6 weeks following injection of hyaluronic acid gel vs. saline.
3 secondary outcomes
Dry Eye
Time frame: 6 weeks post injection.
Quality of life
Time frame: 6 weeks
Complications
Time frame: 6 weeks
Results and safety
The study was stopped early (reason given: recruitment challenges). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
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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.
Daniel Rootman principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hyaluronic Acid Gel injection and Saline injection in people with Thyroid Eye Disease, run by University of California, Los Angeles at 2 sites in United States.
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 3 inclusion and 6 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: stopped early, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: recruitment challenges). Results are not available in the source record.
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?
Upper eyelid scleral show and marginal reflex distance 1 in mm (time frame: 6 weeks after injection). 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 4 Oct 2021.