Evaluation of Mesenchymal Stem Cell Eye Injections for Dry Eye Disease in Patients with Graft-versus-Host Disease Who Haven’t Responded to Standard Treatments

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What is this study about?

This clinical trial is evaluating the effectiveness and safety of Allogeneic Mesenchymal Stem Cell (MSC) eye injections for treating dry eye disease in patients with Graft-versus-Host Disease (GvHD). Graft-versus-Host Disease is a condition that can occur after a bone marrow or stem cell transplant, where the donated cells attack the recipient’s body. When it affects the eyes, it can cause severe dry eye disease, which includes symptoms like eye irritation, burning, and vision problems.

The purpose of this study is to determine if subconjunctival (under the eye’s membrane) injections of stem cells can improve the signs and symptoms of severe dry eye disease that hasn’t responded to conventional treatments. The study will test two different doses of stem cells (6.25 million and 12.5 million) to see which works better.

During the trial, participants will receive ASC (adipose-derived stem cell) injections in their eyes and will be monitored for improvements in various aspects of eye health, including the integrity of the eye surface, tear production, redness of the eye membrane, and function of the oil-producing glands in the eyelids. Researchers will also collect tear and blood samples to analyze inflammation markers and identify potential new ways to track disease improvement.

1 Initial Visit and Treatment

After joining the study, you will receive a subconjunctival injection (an injection under the membrane covering your eye) of allogeneic adipose-derived adult mesenchymal stem cells (eASC). These are stem cells derived from fat tissue of donors that can help reduce inflammation.

Depending on which treatment group you are assigned to, you will receive either a low dose (6.25 million stem cells) or a high dose (12.5 million stem cells) in both eyes.

Before receiving the treatment, if you are a woman of childbearing potential, you will need to take a pregnancy test if more than 28 days have passed since your baseline assessment.

2 Continuing Current Medications

Throughout the trial, you will continue using your current ocular lubricants at least 4 times daily as you were before joining the study.

Any other eye medications you were using before the trial (such as blood derivatives, insulin eye drops, topical cyclosporine or tacrolimus) will be continued at the same dosage.

If you are on topical corticosteroids, you will maintain the same stable dose that you were on for at least one month prior to joining the trial.

Your systemic medications for chronic Graft-versus-Host Disease will remain unchanged from what you were taking for at least one month before joining the study.

3 Follow-up Assessments

During follow-up visits, several measurements will be taken to evaluate how well the treatment is working:

Your corneal surface will be examined using fluorescein staining to check for improvements in superficial punctate keratitis (small dots of damage on the cornea) and any epithelial defects (areas where the cornea’s surface layer is damaged).

Tear production will be measured using the Schirmer test, which involves placing a small strip of filter paper under your lower eyelid after applying topical anesthetic.

The redness of your eyes (conjunctival hyperemia) will be evaluated using the Efron scale.

Your Meibomian glands (oil-producing glands in your eyelids) will be assessed.

The central cornea will be examined using in vivo confocal microscopy, which provides detailed images of your cornea to check for changes in the epithelial cells, dendritic cells, and nerve structures.

You will complete several questionnaires to assess your symptoms, including the OSDI (Ocular Surface Disease Index), mSIDEQ, NRS, WFPRS, and CDES-Q.

4 Sample Collection

Tear samples will be collected to analyze the presence and concentration of 48 inflammation-related molecules.

Blood samples will also be taken to measure the same inflammatory markers in your serum.

These samples will help researchers understand how the treatment is affecting the inflammatory response in your eyes and body.

5 Monitoring for Side Effects

Throughout the trial, you will be monitored for any adverse events related to the stem cell injection.

It’s important to report any new symptoms or changes in your condition to the study team during your follow-up visits.

6 Trial Completion

The clinical trial is expected to run until June 30, 2028, though your individual participation may not last this entire period.

At the end of your participation, a final assessment will be conducted to evaluate the overall effectiveness and safety of the treatment for your dry eye disease related to Graft-versus-Host Disease.

Who Can Join the Study?

You must be over 18 years old and able to understand and sign the informed consent form.
You must have severe chronic Graft versus Host Disease (cGVHD) with severe dry eye disease in both eyes that has lasted more than 3 months.
Your dry eye condition must be objectively confirmed by a score higher than 2 on the Oxford scale (a test that measures damage to the eye surface) and/or have an epithelial defect (damage to the eye’s surface layer).
You must have severe dry eye symptoms, scoring more than 33 points on the OSDI questionnaire (a survey that measures dry eye severity).
You must have previously been treated for at least three months with blood derivatives (like serum eye drops) and/or insulin eye drops and topical cyclosporine or tacrolimus, unless you couldn’t tolerate these treatments.
You must be using artificial tears or lubricating eye drops at least 4 times a day and still have severe dry eye symptoms.
If you’re using topical corticosteroids (steroid eye drops), you must have been on a stable dose for at least one month before joining the study.
You must be able to maintain the same doses and frequency of all your eye medications throughout the trial, unless your doctor determines a change is needed.
Your systemic treatment for chronic GVHD must have been stable for at least one month before joining the study.
If you’re a woman who can become pregnant, you must have a negative pregnancy test before starting the study and agree to use contraception during the study.

Who Cannot Join the Study?

People who are pregnant or breastfeeding cannot participate.
If you have an eye infection or inflammation that is not related to your condition, you cannot join the study.
If you have had eye surgery in the past 3 months, you are not eligible.
People with severe damage to the surface of the eye (called corneal ulceration) cannot participate.
If you have uncontrolled glaucoma (high pressure in the eye that can damage vision), you cannot join.
People with active eye cancer are excluded from the study.
If you have a known allergy to the study medication or its components, you cannot participate.
People who are currently participating in another clinical trial cannot join this study.
If you have a condition that the study doctor believes would interfere with the study or put your health at risk, you may be excluded.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Hospital Universitario De Salamanca	Salamanca	Spain

Other Sites

Site Name	City	Country	Status
Hospital General Universitario Gregorio Maranon	Madrid	Spain

Trial status

Country	Status	Recruitment Start
Spain	Not yet recruiting	16.06.2025

Trial locations

Investigated drugs:

Allogeneic Adipose-Derived Adult Mesenchymal Stem Cells Expanded

Mesenchymal Stem Cells (MSC) are special cells that can help repair damaged tissues. In this trial, these stem cells are injected into the eye to treat severe dry eye disease caused by Graft-versus-Host Disease (GvHD). GvHD is a condition that can occur after a bone marrow or stem cell transplant when the donor cells attack the recipient’s body. The stem cells used in this treatment are allogeneic, which means they come from a donor rather than the patient’s own body.

Investigated diseases:

Dry eye

Dry eye disease – A condition characterized by a lack of adequate lubrication and moisture on the surface of the eye. It occurs when tears are not able to provide adequate lubrication, either because of insufficient tear production or increased tear evaporation. The condition can lead to inflammation and damage to the surface of the eye, resulting in discomfort, visual disturbances, and potential damage to the ocular surface. Symptoms typically include a scratchy sensation, burning, redness, and blurred vision that may worsen throughout the day.

Chronic Graft versus Host Disease (cGVHD) – A long-term complication that can occur after allogeneic stem cell or bone marrow transplantation. In this condition, the donor’s immune cells recognize the recipient’s tissues as foreign and attack them. cGVHD can affect various organs, including the eyes, skin, mouth, liver, lungs, and digestive tract. When it affects the eyes, it often causes severe dry eye disease due to inflammation and scarring of the lacrimal glands that produce tears. The ocular manifestations typically develop gradually and may progress to cause significant discomfort and visual impairment.

Trial ID:

2024-519772-10-00

Protocol code:

TERAV_24-01_EICRxEYE

Trial Phase:

Therapeutic exploratory (Phase II)

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Evaluation of Mesenchymal Stem Cell Eye Injections for Dry Eye Disease in Patients with Graft-versus-Host Disease Who Haven’t Responded to Standard Treatments

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