Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease (HALR)

Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease (HALR)

This study is currently recruiting participants. (see Contacts and Locations)

Verified December 2014 by University of California, Los Angeles

Sponsor:

University of California, Los Angeles 

Information provided by (Responsible Party):

Daniel Rootman, University of California, Los Angeles

ClinicalTrials.gov Identifier:

NCT01738243

First received: October 6, 2012

Last updated: December 2, 2014

Last verified: December 2014 

History of Changes

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  Purpose

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).

Condition	Intervention	Phase
Thyroid Eye Disease	Drug: Hyaluronic Acid Gel injection Drug: Saline injection	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Phase IV Study of Hyaluronic Acid Gels for Upper Lid Retraction in Active Stage Thyroid Eye Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Graves disease Lenz microphthalmia syndrome oculofaciocardiodental syndrome

MedlinePlus related topics: Eye Diseases Thyroid Diseases

Drug Information available for: Thyroid Hyaluronic Acid Hyaluronate Sodium

Genetic and Rare Diseases Information Center resources: Graves' Disease

U.S. FDA Resources 

Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:

• Upper eyelid scleral show and marginal reflex distance 1 in mm [ Time Frame: 6 weeks after injection ] [ Designated as safety issue: No ]
  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.

Secondary Outcome Measures:

• Dry Eye [ Time Frame: 6 weeks post injection. ] [ Designated as safety issue: No ]
  We will measure severity of dry eye signs using the Oxford staining scale and the Ocular surface disease index
• Quality of life [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  The Graves Orbitopathy Quality of Life (GO-QOL) survey will be given to subjects at entry and at 6 weeks.
• Complications [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  Complications including null effect, ecchymosis, retrobulbar hemorrhage, cranial nerve injury and extraocular muscle dysfunction will be monitored and reported

Estimated Enrollment:	40
Study Start Date:	December 2012
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Unilateral Upper Eyelid Retraction 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	Drug: Hyaluronic Acid Gel injection 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. Other Names: Restylane Belotero Drug: Saline injection 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. Other Name: Normal saline
Experimental: Bilateral Upper Eyelid Retraction 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	Drug: Hyaluronic Acid Gel injection 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. Other Names: Restylane Belotero Drug: Saline injection 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. Other Name: Normal saline

  Eligibility

Ages Eligible for Study:	21 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Active stage TO as determined by symptom onset of under 9 months.
2. Upper eyelid retraction of 1mm or greater in one or both eyes.
3. Complaints of either significant ocular symptoms (despite appropriate use of ocular lubricants), or cosmetic deformity associated with the eyelid retraction.

Exclusion Criteria:

1. Age less than 21 years: due to lack of data on safety for HAG fillers in pediatric population
2. Age over 65 years of age: as HAG filler effect may be different in this population
3. Are pregnant or nursing: as there is little safety data on potential teratogenicity of HAG fillers
4. Have a demonstrated allergy to HAG fillers or lidocaine
5. Have a current infection, skin sore, pimple, rash, hive or cyst over the injection site: to avoid worsening the infection or transmitting it
6. Have a bleeding disorder or currently taking blood thinning medications such as Coumadin, heparin or acetylsalicylic acid on a daily basis.

  Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies. 

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738243

Locations

United States, California
Jules Stein Eye Institute	Recruiting
Los Angeles, California, United States, 90095
Contact: Dia Cervantes    310-206-9727    cervantes@jsei.ucla.edu
Principal Investigator: Daniel B Rootman, MD MSc
The Jules Stein Eye Institute at UCLA	Enrolling by invitation
Los Angeles, California, United States, 90095

Sponsors and Collaborators

University of California, Los Angeles

Investigators

Principal Investigator:	Daniel Rootman	University of California, Los Angeles

  More Information

No publications provided 

Responsible Party:	Daniel Rootman, Clinical Instructor, University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT01738243     History of Changes
Other Study ID Numbers:	PRE#12-003174
Study First Received:	October 6, 2012
Last Updated:	December 2, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:

Thyroid Thyroid Eye Disease Thyroid Orbitopathy Eyelid Retraction Upper Eyelid Retraction

Additional relevant MeSH terms:

Eye Diseases Graves Ophthalmopathy Autoimmune Diseases Endocrine System Diseases Exophthalmos Eye Diseases, Hereditary Goiter Graves Disease Hyperthyroidism Immune System Diseases	Orbital Diseases Thyroid Diseases Hyaluronic Acid Adjuvants, Immunologic Immunologic Factors Pharmacologic Actions Physiological Effects of Drugs Protective Agents Viscosupplements

ClinicalTrials.gov processed this record on March 23, 2015