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Dry EyeEarly Phase 1MESADDENCT03878628

Treatment With Allogeneic Adipose-derived Mesenchymal Stem Cells in Patients With Aqueous Deficient Dry Eye Disease

A Early Phase 1 study testing Adipose tissue-derived mesenchymal stem cells in people with Dry Eye and Kerato Conjunctivitis Sicca, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objective of this study is to assess the safety and feasibility of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) injected into the lacrimal gland in a smaller groups of 7 patients with Aqueous Deficient Dry Eye Disease (ADDE) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Adipose tissue-derived mesenchymal stem cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteDenmark
Study dates
16 Oct 2019to 20 Feb 2023
Phase
Early Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • OSDI-score > 30
  • Schirmer's test 2-5 mm in 5 minutes
  • TBUT < 10 sec.

Who cannot join

  • Previously established allergies to Oxybuprocaine or DMSO (rare)
  • Reduced immune response (e.g. HIV positive)
  • Pregnancy or planned pregnancy within the next 2 years
  • Breastfeeding
  • Treatment with an anticoagulant that cannot be stopped during the intervention period
  • Treatment with systemic medication known to reduce tear production (with an odds ratio >2,0 (3)): anxiolytics, antipsychotics, and inhaled steroids.
  • Topical treatment with eye drops other than lubricants
  • Any other disease/condition judged by the investigator to be grounds for exclusion, such as infection in or around the eye

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Rigshospitalet

    Copenhagen, DK, 2200

Other trials in Denmark

About this study

The objective of this study is to assess the safety and feasibility of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) injected into the lacrimal gland in a smaller groups of 7 patients with Aqueous Deficient Dry Eye Disease (ADDE)

Read the detailed description

Dry eye disease (DED) is a very common problem seen in patients all over the world. According to an older study the prevalence of DED in a Danish population 30-60 years of age was 11%. Aqueous tear deficient dry eye (ADDE) is a subtype of DED in which the tear production in the lacrimal gland (LG) is impaired. Current treatment of ADDE is only to relieve symptoms as a curative treatment of ADDE does not exist.

Mesenchymal stem cells (MSCs) reside in almost all connective tissues and are multipotent stem cells with the capacity to differentiate into several kinds of tissue. Several studies have shown that MSCs reduces inflammation in various diseases. Adipose tissue-derived MSCs (ASCs) have gained considerable attention, since they are readily available from the abdominal fat where it is most easily collected and expanded. In resting MSCs, MHC class II is not expressed on the surface, which reduces the inherent immunogenicity of the cells. This supreme attribute allows allogeneic MSC transplantation. Treatment with allogeneic MSCs have been investigated in an extensive number of human subjects for various conditions in clinical trials and no documented adverse events related to an anti-donor immune response exist. One potential advantage of treatment with allogeneic cells is the possibility of their use as an "off-the-shelf" therapeutic agent, avoiding the need for tissue collection and culture to delay and increase the cost of treatment. It has also been suggested that the function of autologous MSCs could be impaired in patients with comorbidities or advanced age.

In canines as in humans the most common cause of ADDE is an immune-mediated inflammatory response targeting the LG. Two studies with injection of allogeneic ASCs from healthy donors in a total of 48 eyes in 27 canines with ADDE have been performed with a significant increase in tear production and no observed adverse events to the treatment.

Studies with injection of ASCs into the human LG has never been conducted. This present study will test the hypothesis that injection of allogeneic ASCs into the LG in patients suffering from ADDE is safe and increases tear production and reduces inflammation resulting in increased ocular comfort.

7 patients with severe ADDE from Dept. of Ophthalmology, Rigshospitalet-Glostrup, will be recruited if they are 1: eligible for the study and 2: sign the informed consent form.

At inclusion the participants will fill out the Ocular Surface Disease Index (OSDI) questionnaire and undergo an eye examination in the following order:

measurement of tear osmolarity (TearLab™), tear break-up time (TBUT), ocular surface staining according to the Ocular SICCA Grading Score, and Schirmer's I test.

After a maximum of 14 days from screening all participants will receive an injection with ASCs into the lacrimal gland on one eye. If both eyes fulfill the eligibility criteria the most affected eye with the lowest tear production assessed with the Schirmer's I test will be the study eye; the contralateral eye will not be treated but examined according to the same protocol as the study eye at each follow-up.

The product used is CSCC_ASC(22) and the dose injected contains approximately 11 million ASCs per LG in a suspension with a total volume of 0.5 ml.

1 week (±2 days), 4 weeks (±4 days), and 4 months (±7 days) after intervention the participants are followed up with eye examination as described above, OSDI questionnaire, and blood test. At 4 months the primary outcomes of safety will be evaluated.

End of trial is defined as last participant's last visit (LPLV) at 3 years late follow-up.

Being tested
Adipose tissue-derived mesenchymal stem cells
Medical subject headings
Dry Eye Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Adipose tissue-derived mesenchymal stem cellsDrug

    CSCC_ASC(22), a ready-to-use suspension containing 22 million adipose tissue-derived mesenchymal stem cells per millilitre

Study groups in NCT03878628
Study groupRoleWhat they receive
Adipose tissue-derived mesenchymal stem cellsExperimentalApproximately 11 million ASCs in a 0.5 ml suspension
Receives: Drug: Adipose tissue-derived mesenchymal stem cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pain at injection site: grade

    grade 1: mild pain, grade 2: moderate pain, grade 3: severe pain

    Measured: 4 months after treatment

  2. Infection at injection site

    grade 1: localized; local intervention indicated, grade 2: oral intervention indicated (antibiotic, antifungal, antiviral), grade 3: intravenously administered (IV) antibiotic, antifungal, or antiviral agent indicated; or operative intervention indicated, grade 4: life-threatening consequences; urgent intervention needed.

    Measured: 4 months after treatment

  3. Bleeding at injection site

    Grade 1: Mild bleeding; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization indicated.

    Measured: 4 months after treatment

  4. Eyelid function disorder

    Grade 1: Asymptomatic; clinical or diagnostic observations only; intervention not indicated;

    Grade 2: Symptomatic; nonoperative intervention indicated; limiting instrumental ADL;

    Grade 3: Limiting self care ADL; operative intervention indicated.

    Measured: 4 months after treatment

  5. Periorbital edema

    Grade 1: Soft or non-pitting;

    Grade 2: Indurated or pitting edema; topical intervention indicated;

    Grade 3: Edema associated with visual disturbance; increased intraocular pressure, glaucoma or retinal hemorrhage; optic neuritis; diuretics indicated; operative intervention indicated.

    Measured: 4 months after treatment

  6. Ocular discomfort

    grade 1: mild discomfort,

    grade 2: moderate pain,

    grade 3: disabling pain.

    Measured: 4 months after treatment

  7. Flu-like symptoms

    grade 1: Mild flu-like symptoms present;

    grade 2: Moderate flu-like symptoms, limiting self care ADL;

    grade 3: Severe flu-like symptoms, limiting self care ADL)

    Measured: 4 months after treatment

  8. Fever

    grade 1: 38,0-39,0 Cº; grade 2: >39,0-40,0 Cº; grade 3: >40,0 Cº for ≤ 24 hours; grade 4: >40,0 Cº for > 24 hours

    Measured: 4 months after treatment

Secondary outcomes (5)

  1. OSDI questionnaire

    Change in severity of dry eye symptoms as assessed with the OSDI questionnaire with a score of 0-100, where 0 is "no symptoms" and 100 is "severe symptoms"

    Measured: 4 months after treatment

  2. Schirmer's I test

    Change in tear production as evaluated with the Schirmer's I test

    Measured: 4 months after treatment

  3. Tear osmolarity

    Change in tear osmolarity measured with TearLab(TM)

    Measured: 4 months after treatment

  4. Ocular SICCA Grading Score

    Change in objective signs of DED as evaluated with the Ocular SICCA Grading Score from 0-12 where 0 is "no staining of the ocular surface" and 12 is "severe staining of the ocular surface"

    Measured: 4 months after treatment

  5. HLA anti-bodies

    Development of anti-HLA anti-bodies evaluated with Luminex HLA anti-body screening

    Measured: 4 months after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2019
  2. Study start16 Oct 2019
  3. Primary completion30 Jun 2020
  4. Study completion20 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03878628
Sponsor's protocol ID
001-2018
Acronym
MESADDE
Status last verified
Nov 2023
First submitted
12 Mar 2019
Last updated
18 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Adipose tissue-derived mesenchymal stem cells in people with Dry Eye and Kerato Conjunctivitis Sicca, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

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 8 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 18 Nov 2023. 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 Denmark. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 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?

Pain at injection site: grade (time frame: 4 months after treatment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03878628.

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 18 Nov 2023.

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