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Central Retinal Vein OcclusionPhase 1/2TRUSTNCT03981549

Treatment of Central Retinal Vein Occlusion Using Stem Cells Study

A Phase 1/2 study testing Autologous Bone Marrow CD34+ Stem Cells in people with Central Retinal Vein Occlusion, run by The Emmes Company, LLC at 1 site in United States.

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

This study evaluates whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Central Retinal Vein Occlusion
What is being tested?
Autologous Bone Marrow CD34+ Stem Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
1 siteUnited States
Study dates
22 Oct 2019to 9 Nov 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Clinical diagnosis of central retinal vein occlusion (CRVO) confirmed by review of medical records and screening assessment.
  • Best Corrected Visual Acuity (BCVA) obtained during the screening period is in the range of 20/40+ to 20/400- (ETDRS letter score in the range of 18 to 73, inclusive).
  • Duration of vision loss from CRVO >= 6 months to <=42 months.

Who cannot join

  • Previous eye treatment with intravitreal or periocular steroids, laser or intraocular surgery within 6 months prior to enrollment (i.e., date ICF signed) or treatment expected to be given during the study period.
  • For eyes requiring treatment to prevent recurrent macular edema, on-going intravitreal anti-VEGF treatment is expected to be given at an interval < every 8 weeks during the study period or anti-VEGF therapy was started less than 24 weeks prior to informed consent.
  • History of concurrent ocular herpes infection.
  • Active non-herpetic eye infection diagnosed within 8 weeks from enrollment (i.e., date Informed Consent Form (ICF) signed).
  • Glaucoma requiring treatment with more than 2 medications, laser or intraocular surgery.
  • Active uveitis or history of recurrent uveitis or uveitis involving the posterior segment.
Show all 38Show fewer
  • Presence of cataract that is impairing vision.
  • Presence of lens or lens implant subluxation.
  • History of ocular trauma that is currently impairing vision.
  • Any concurrent optic nerve or retinal disease that is visually significant or likely to progress to visual significance during the 1-year study follow-up. The excluded eyes include eyes with AREDS category 2 to 3 age-related macular degeneration (AMD) with foveal involvement of drusen or RPE changes, and any AREDS category 4 AMD eyes. For eyes with ERM, the excluded eyes include eyes with OCT evidence of foveal deformation. For optic nerve disease, eyes with any associated visual field deficit or history of associated CNVM are excluded. For glaucoma eyes, eyes requiring glaucoma laser trabeculectomy or glaucoma surgery to maintain IOP are excluded.
  • Active retinal or iris neovascularization.
  • Macular edema requiring on-going therapy or where treatment is expected during the study period, with the exception of anti-VEGF treatment given at an interval of 8 weeks or greater.
  • Significant media opacity precluding view of the fundus for examination, photography or optical coherence tomography (OCT) including cataract and vitreous haze.
  • High myopia (>= 9 diopters)
  • Amblyopia
  • Other cause contributing to vision loss at screening.
  • History of any of the following procedures: corneal transplant, glaucoma surgery, or intraocular silicone oil.
  • Participant-level Inclusion/Exclusion Criteria:
  • Participant-level inclusion criteria:
  • Age >=18 years
  • Female participants of child-bearing potential must not be pregnant or breastfeeding and have a negative urine pregnancy test within 14 days prior to sham injection and/or CD34+ cell injection.
  • Females of childbearing potential must have had a hysterectomy, be completely abstinent from intercourse or must agree to practice effective contraception for the duration of the study. Acceptable methods of contraception include hormonal contraception, intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation).
  • Able and willing to sign informed consent.
  • Able to keep follow-up appointments for at least 12 months as determined by the investigator.
  • Participant-level exclusion criteria:
  • Concurrent treatment with an investigational drug or device.
  • Concurrent use of systemic immunosuppressive therapy or history of use within 3 months prior to enrollment (i.e., date ICF signed).
  • Concurrent use of anticoagulation therapy except for aspirin without an acceptable safe stopping plan for study treatments.
  • Known history of coagulopathy or other hematologic abnormality that may put participant at risk for bleeding or infection or raise concerns about quality or quantity of CD34+ cells isolated.
  • History of allergy to fluorescein dye.
  • Participant who has had a prior or concomitant malignancy with the exception of the following: 1) adequately treated basal or squamous cell carcinoma of the skin, or 2) any other malignancy from which the patient has remained disease free for more than five years.
  • Current active systemic infection as evidenced by fever greater than 100.4 or any evidence of systemic infection as determined by the study physician.
  • Any diagnosis of active infection or vaccination within 8 weeks of study treatment.
  • Diabetes mellitus with known systemic complications by self-report or physician-determined by medical history or examination.
  • History of prior radiotherapy to head/neck area.
  • Poorly controlled hypertension with systolic > 180 or diastolic > 95.
  • Serious medical or psychiatric condition that, in the opinion of the Investigator, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study.
  • Any physical characteristic that precludes ability to perform study diagnostic testing.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Department of Ophthalmology & Vision Science, University of California Davis Eye Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I/II Randomized, Prospective, Double-masked, Sham-controlled Study of Intravitreal Autologous Bone Marrow CD34+ Stem Cell Therapy for Central Retinal Vein Occlusion

This study evaluates whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Half of the participants will receive immediate cellular therapy followed by sham therapy 6 months later, while the other half will receive immediate sham therapy followed by cellular therapy 6 months later. Participants will be followed for a total of 1 year.

Read the detailed description

The goal of this phase I/II prospective, randomized, sham-controlled, double-masked clinical trial is to determine whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Retinal Vein Occlusion (RVO) is a leading retinal vascular cause of vision loss in the elderly. CD34+ stem cells in human bone marrow are mobilized into the circulation in response to tissue ischemia for tissue revascularization and repair. Since local delivery of CD34+ stem cells benefits ischemic tissue, intravitreal delivery of CD34+ stem cells may benefit vision and retinal ischemia in eyes with RVO. A pilot clinical trial has shown no major safety or feasibility concerns using intravitreal autologous CD34+ bone marrow stem cells. In this proposed expanded phase I/II study, 20 participants (20 eyes) with persistent vision loss from CRVO will be enrolled and followed for 1 year.

Participants will be randomized 1:1 to immediate cell therapy/deferred sham therapy or immediate sham therapy/deferred cell therapy. At month 6, the cell treated eye will receive sham treatment and the sham treated eye will get cell therapy. The cellular therapy involves bone marrow aspiration, isolation of CD34+ cells from the aspirate under Good Manufacturing Practice (GMP) conditions, and intravitreal injection of isolated CD34+ cells. The sham therapy involves a sham bone marrow aspiration with penetration of the skin but no penetration of the bone and a sham intravitreal injection without penetrating the eye. The participant, examining ophthalmologist, visual acuity examiner, photographers and OCT, perimetry, and electroretinography (ERG) technicians will remain masked to study treatment assignment for study duration. A comprehensive eye examination with ETDRS best-corrected visual acuity, optical coherence tomography (OCT) and OCT angiography (OCTA), autofluorescence, fundus photography, fluorescein angiography, microperimetry, and electroretinography will be performed at baseline and serially. A subset of participants with good fixation on microperimetry and clear media on exam and commercial-grade OCTA and who give consent will have ultra-high resolution cellular retinal imaging using research-grade OCT and OCTA and adaptive optics-OCT at baseline. Participants with high quality images will have repeat imaging at 1 month after stem cell treatment, with at least 2 of the participants randomized to the deferred cellular therapy arm also having imaging 1 month after sham therapy. Post-release flow cytometry characterization will be performed to determine the composition of the CD34+ enriched final product in terms of hematopoietic versus angiogenic stem cells based on cell surface markers (i.e., CD133(+)/CD45(+)/CD34(+) vs CD31(+)/VEGFR-2(+)/CD45(-)/CD34(+)). The long-term objective is to determine whether intravitreal autologous CD34+ cell therapy can minimize, or reverse vision loss associated with retinal ischemia without compromising safety.

Being tested
Autologous Bone Marrow CD34+ Stem Cells, Sham Therapy
Keywords
Central Retinal Vein Occlusion, Retinal Vein Occlusion, Retinal Diseases, Eye Diseases, CD34+ Stem Cell Therapy, Autologous Bone Marrow Stem Cells, Stem Cells
Medical subject headings
Retinal Vein Occlusion, Retinal Diseases, Eye Diseases

What participants receive

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

  • Autologous Bone Marrow CD34+ Stem CellsBiological

    Single intravitreal injection of autologous bone marrow CD34+ stem cells. The number of cells to be injected per eye will range from 800,000 to 10 million, depending on the yield of the bone marrow aspiration and the isolation procedure.

  • Sham TherapyBiological

    Sham bone marrow aspiration procedure that penetrates the skin, but does not penetrate the bone followed by sham intravitreal injection without penetration of the eye

Study groups in NCT03981549
Study groupRoleWhat they receive
Immediate Cellular Therapy / Deferred Sham TherapyActive comparatorAt baseline: Bone marrow aspiration followed by intravitreal injection of CD34+ cells. At 6 months: Sham bone marrow aspiration and sham intravitreal injection.
Receives: Biological: Autologous Bone Marrow CD34+ Stem Cells; Biological: Sham Therapy
Immediate Sham Therapy / Deferred Cellular TherapySham comparatorAt baseline: Sham bone marrow aspiration followed by sham intravitreal injection. At 6 months: Bone marrow aspiration followed by intravitreal injection of CD34+ cells.
Receives: Biological: Autologous Bone Marrow CD34+ Stem Cells; Biological: Sham Therapy

What is being measured

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

  1. Incidence and Severity of Ocular and Systemic Adverse Events

    The primary safety outcome will be assessed at month 6. Adverse events (AE) that occur during the first 6 months of the trial will be broken down by whether the AE occurred following the sham or cellular treatment to assess differences in the adverse event experience between the cellular and sham therapies.

    Measured: Months 0 to 6

  2. Feasibility of the Stem Cell Therapy

    Number of CD34+ cells isolated from the bone marrow aspirate and number of cells injected into the eye

    Measured: Day 0 and Day 182

Secondary outcomes (20)

  1. Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Letter Score

    Mean change from baseline of visual acuity letter score at Month 6. The measure is calculated by subtracting the baseline visual acuity letter score from the month 6 visual acuity letter score. The participant is refracted for best corrected vision, and then reads single letters from the ETDRS charts using a visual acuity light box at a 4 meter distance (or 1 meter for participants with sufficiently reduced vision) according to a specific algorithm. A letter score is provided that ranges from 0 (unable to read any letters) to 100. A visual acuity letter score of 85 corresponds to a visual acuity of 20/20 as a Snellen equivalent. Higher is better.

    Measured: Months 0 to 6

  2. Change in % Reduced Sensitivity

    Mean change from baseline of % reduced sensitivity at Month 6 as measured by microperimetry (decrease is better)

    Measured: Months 0 to 6

  3. Change in Average Threshold

    Mean change from baseline of average threshold (dB) at Month 6 as measured by microperimetry (increase is better)

    Measured: Months 0 to 6

  4. Change in Percent Normal Amplitude for ERG+OP (Oscillatory Potential) A-wave Under Scotopic Conditions

    Mean change from baseline of percent of normal amplitude for ERG+OP a-wave under scotopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  5. Change in Percent Normal Amplitude for ERG+OP B-wave Under Scotopic Conditions

    Mean change from baseline of percent of normal amplitude for ERG+OP b-wave under scotopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  6. Change in Percent Normal Latency of ERG+OP A-wave Under Scotopic Conditions

    Mean change from baseline of percent normal latency of ERG+OP a-wave under scotopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  7. Change in Percent Normal Latency of ERG+OP B-wave Under Scotopic Conditions

    Mean change from baseline of percent normal latency of ERG+OP b-wave under scotopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  8. Change in Percent Normal Amplitude for A-wave Under Photopic Conditions

    Mean change from baseline of percent normal amplitude for a-wave under photopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  9. Change in Percent Normal Amplitude for B-wave Under Photopic Conditions

    Mean change from baseline of percent normal amplitude for b-wave under photopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  10. Change in Percent Normal Latency for A-wave Under Photopic Conditions

    Mean change from baseline of percent normal latency for a-wave under photopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  11. Change in Percent Normal Latency for B-wave Under Photopic Conditions

    Mean change from baseline of percent normal latency for b-wave under photopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  12. Change in Percent Normal Flicker Amplitude

    Mean change from baseline in percent normal flicker amplitude at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  13. Change in Flicker Latency Trough

    Mean change from baseline of latency trough at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  14. Change in Percent Normal Amplitude for A-wave Under Scotopic Conditions

    Mean change from baseline of percent normal amplitude for a-wave under scotopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  15. Change in Percent Normal Latency of A-wave Under Scotopic Conditions

    Mean change from baseline of percent normal latency of a-wave under scotopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  16. Change in Percent Normal Amplitude for B-wave Under Scotopic Conditions

    Mean change from baseline of percent normal amplitude for b-wave under scotopic conditions at Month 6 as measured by Full-field ERG (increase is better)

    Measured: Months 0 to 6

  17. Change in Percent Normal Latency for B-wave Under Scotopic Conditions

    Mean change from baseline of percent normal latency for b-wave under scotopic conditions at Month 6 as measured by Full-field ERG (decrease is better)

    Measured: Months 0 to 6

  18. Foveal Avascular Zone Integrity

    Number of study eyes in each of the following categories as it relates to the integrity of the foveal avascular zone: Intact, Questionable, Disrupted (<900 microns), Disrupted (900-1800 microns), Disrupted (>1800 microns), and Cannot grade. Measured at Month 6 by fluorescein angiogram

    Measured: 6 months

  19. Change in Area of Non-perfusion Within ETDRS Grid

    Mean change from baseline of area of non-perfusion within ETDRS grid at Month 6 as measured by fluorescein angiogram (decrease is better)

    Measured: Months 0 to 6

  20. Change in Area of Non-perfusion Within Networc Grid

    Mean change from baseline of area of non-perfusion within Networc grid at Month 6 as measured by fluorescein angiogram (decrease is better)

    Measured: Months 0 to 6

Timeline

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

  1. First posted11 Jun 2019
  2. Study start22 Oct 2019
  3. Primary completion7 Nov 2023
  4. Study completion9 Nov 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
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03981549
Sponsor's protocol ID
TRUST
Other IDs
1UG1EY026876-01A1, 1UG1EY028517-01
Acronym
TRUST
Status last verified
Nov 2024
First submitted
6 Jun 2019
Last updated
2 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: TRUST will follow specific plans for sharing of research data under the guidance of NIH's 2003 Data Sharing Policy. After analysis, the final data set can be provided after appropriate procedures are implemented to preserve the anonymity of the records, specifically where protected health information (PHI) is required. Upon request, anonymized data will be shared under confidentiality agreements with researchers interested in the project.

Publications

  • Park SS, Bauer G, Abedi M, Pontow S, Panorgias A, Jonnal R, Zawadzki RJ, Werner JS, Nolta J. Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest Ophthalmol Vis Sci. 2014 Dec 9;56(1):81-9. doi: 10.1167/iovs.14-15415.

    PubMed 25491299

  • Park SS, Bauer G, Fury B, Abedi M, Perotti N, Colead-Bergum D, Nolta JA. Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa. Ophthalmol Sci. 2024 Jul 31;5(1):100589. doi: 10.1016/j.xops.2024.100589. eCollection 2025 Jan-Feb.

    PubMed 39328826

  • Romano F, Lamanna F, Gabrielle PH, Teo KYC, Battaglia Parodi M, Iacono P, Fraser-Bell S, Cornish EE, Nassisi M, Viola F, Agarwal A, Samanta A, Chhablani J, Staurenghi G, Invernizzi A. Update on Retinal Vein Occlusion. Asia Pac J Ophthalmol (Phila). 2023 Mar-Apr 01;12(2):196-210. doi: 10.1097/APO.0000000000000598. Epub 2023 Feb 14.

    PubMed 36912792

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous Bone Marrow CD34+ Stem Cells in people with Central Retinal Vein Occlusion, run by The Emmes Company, LLC at 1 site 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 38 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 2 Dec 2024. 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 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Incidence and Severity of Ocular and Systemic Adverse Events (time frame: Months 0 to 6). The study lists 2 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 NCT03981549, which also lists 3 linked publications.

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 2 Dec 2024.

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