Retinal DetachmentNCT03332758
Inflammasomes in Cell Death in FTMH, ERM, and RRD
An observational study of Retinal Detachment and Full Thickness Macular Hole, run by Allen C. Ho, MD at 1 site in United States.
Trial summary
Prospective study evaluating the role of inflammasomes in cell death in retinal detachment, full thickness macular hole, and epiretinal membrane. The investigators are collecting vitreous and subretinal fluid samples from patients with these conditions and evaluating activity of the inflammasome pathway with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Retinal Detachment, Full Thickness Macular Hole, Epiretinal Membrane
- What is being tested?
- Pars plana vitrectomy and External drainage
- Type of treatment
- Surgery or procedure
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2017to 1 May 2018
- Phase
- Observational
- 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
Study population: Adults with retinal detachment, macular hole, or epiretinal membrane.
Who may be able to join
- Patient of the Wills Eye Hospital Retina service and Mid-Atlantic Retina offices.
- Volunteer patients age 18 years and older.
- Healthy enough to participate in the study.
- Willing and able to consent to participation in the study.
- Diagnosis of rhegmatogenous retinal detachment treated with external drainage of subretainl fluid, rhegmatogenous retinal detachment treated with pars plana vitrectomy, or full thickness macular hole treated with pars plana vitrectomy
Who cannot join
- Presence of tractional retinal detachment
- History of trauma
- Presence of proliferative vitreoretinopathy
- History of prior retinal detachment repair or any prior retina surgery or laser treatment e. Any preexisting retinal disease (including diabetic retinopathy, age related macular degeneration, retinal vein or artery occlusion, other retinal vascular disease, inherited retinal degeneration, uveitis)
Trial locations and contacts
1 site in 1 country.
United States1 site
MidAtlantic Retina-Wills Eye Hospital
Philadelphia, Pennsylvania, 19107
About this study
Official title: Inflammasomes in Cell Death in Macular Hole, Epiretinal Membrane, and Rhegmatogenous Retinal Detachment
Prospective study evaluating the role of inflammasomes in cell death in retinal detachment, full thickness macular hole, and epiretinal membrane. The investigators are collecting vitreous and subretinal fluid samples from patients with these conditions and evaluating activity of the inflammasome pathway with established assays.
Read the detailed description
Photoreceptor cell death is the main cause of vision loss in many retinal disorders, including retinal detachment (RD). While apoptosis is the most studied form of cell death, the investigators believe patients with RDs may have photoreceptor cell death from a distinct pathway of programmed cell death called pyroptosis which also involves an inflammatory response. Pyroptosis is distinct from apoptosis in that it requires the activation of a protein oligomer complex called an inflammasome. The inflammasome is a pro-inflammatory complex composed of apoptosis-associated speck-like protein containing a CARD (ASC), nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor (NLR) family or pyrin and HIN domain (PYHIN) family, and caspase-11. Activation of the inflammasome complex leads to activation of capspase 1 proteolytic activity to cleave and synthesize IL-1β and IL-18. As such the investigators believe inflammasomes and its activated products may play a strong role in the inflammatory and cell death pathway for photoreceptor cells in human retina. Studies using animal models of RD have already confirmed the presence of IL-1β activation2, however, the presence of IL-18 needs to be confirmed in human detached retinas. In a study performed on the detached retinas in mice, researchers were able to show activation of inflammasomes leading to photoreceptor cell death. While researchers are unable to determine the cellular source of the inflammasomes they were able to show that activation inflammasomes closely follows animal models. Currently there is no method to rescue photoreceptors cells from the mediated cell death pathway despite surgical intervention. Thus, current visual prognosis and prevention of further photoreceptor loss due to a RD is likely dependent on the time of surgical intervention before further detachment and further cell death can occur. As such, the purpose of this current study is to confirm the presence of inflammasome activation as well as the synthesis of its products, IL-1β and IL-18, in patients with rhegmatogenous retinal detachments. Both inflammasomes and its products IL-1β and IL-18 may be involved in cell pyroptosis, a programmed cell death distinct from apoptosis. Due to a lack of treatment for the rescue of photoreceptor cells from cell death after a retinal detachment, this study can provide novel strategies to inhibit cell death.
- Being tested
- Pars plana vitrectomy, External drainage
- Keywords
- retinal detachment, inflammasome, macular hole
- Medical subject headings
- Retinal Detachment, Epiretinal Membrane, Retinal Perforations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pars plana vitrectomyProcedure or surgery
Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.
External drainageProcedure or surgery
Standard of care treatment for retinal detachment.
| Study group | Role | What they receive |
|---|---|---|
| RD treated with vitrectomy | Vitreous fluid from retinal detachment treated with pars plana vitrectomy Receives: Procedure: Pars plana vitrectomy | |
| RD treated with external drainage | Subretinal fluid from retinal detachment treated with external drainage. Receives: Procedure: External drainage | |
| Macular holes treated with vitrectomy | Vitreous fluid from patients treated for macular hole Receives: Procedure: Pars plana vitrectomy | |
| ERM treated with vitrectomy | Vitreous fluid from patients treated for epiretinal membrane Receives: Procedure: Pars plana vitrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of inflammasomes and their active products
Presence of inflammasomes and their active products in patients with retinal detachment treated with vitrectomy or external drainage, macular holes treated with vitrectomy, and epiretinal membranes treated with vitrectomy
Measured: Day of surgery
Secondary outcomes (1)
Difference in inflammasome levels among samples
Difference in inflammasome pathway activation between retinal detachment, macular hole, and epiretinal membrane samples
Measured: Day of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start8 Sep 2017
- Primary completion10 Apr 2018
- Study completion1 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Retinal DetachmentStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allen C. Ho, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Mid Atlantic Retina
- Responsible party
- Sponsor-investigator, Allen C. Ho, MD, Wills Eye
- Investigators
- Allen C Ho, MD, Principal investigator, MidAtlantic Retina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332758
- Sponsor's protocol ID
- 17-660E
- Status last verified
- Aug 2018
- First submitted
- 13 Oct 2017
- Last updated
- 17 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: manuscript under development
Publications
Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG. Photoreceptor cell death and rescue in retinal detachment and degenerations. Prog Retin Eye Res. 2013 Nov;37:114-40. doi: 10.1016/j.preteyeres.2013.08.001. Epub 2013 Aug 28.
PubMed 23994436Kataoka K, Matsumoto H, Kaneko H, Notomi S, Takeuchi K, Sweigard JH, Atik A, Murakami Y, Connor KM, Terasaki H, Miller JW, Vavvas DG. Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal detachment-induced photoreceptor cell death. Cell Death Dis. 2015 Apr 23;6(4):e1731. doi: 10.1038/cddis.2015.73.
PubMed 25906154
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammasomes in Cell Death in Macular Hole, Epiretinal Membrane, and Rhegmatogenous Retinal Detachment
- ClinicalTrials.gov ID
- NCT03332758
- Acronym / sponsor ID
- 17-660E
- Keywords
- retinal detachment, inflammasome, macular hole
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Allen C. Ho, MDUniversity, hospital or other
- Collaborators
- Mid Atlantic Retina
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 10 Apr 2018 (actual)
- Study completion
- 1 May 2018 (actual)
- First posted
- 6 Nov 2017 (actual)
- 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.
Prospective study evaluating the role of inflammasomes in cell death in retinal detachment, full thickness macular hole, and epiretinal membrane. The investigators are collecting vitreous and subretinal fluid samples from patients with these conditions and evaluating activity of the inflammasome pathway with established assays.
Detailed description
Photoreceptor cell death is the main cause of vision loss in many retinal disorders, including retinal detachment (RD). While apoptosis is the most studied form of cell death, the investigators believe patients with RDs may have photoreceptor cell death from a distinct pathway of programmed cell death called pyroptosis which also involves an inflammatory response. Pyroptosis is distinct from apoptosis in that it requires the activation of a protein oligomer complex called an inflammasome. The inflammasome is a pro-inflammatory complex composed of apoptosis-associated speck-like protein containing a CARD (ASC), nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor (NLR) family or pyrin and HIN domain (PYHIN) family, and caspase-11. Activation of the inflammasome complex leads to activation of capspase 1 proteolytic activity to cleave and synthesize IL-1β and IL-18. As such the investigators believe inflammasomes and its activated products may play a strong role in the inflammatory and cell death pathway for photoreceptor cells in human retina. Studies using animal models of RD have already confirmed the presence of IL-1β activation2, however, the presence of IL-18 needs to be confirmed in human detached retinas. In a study performed on the detached retinas in mice, researchers were able to show activation of inflammasomes leading to photoreceptor cell death. While researchers are unable to determine the cellular source of the inflammasomes they were able to show that activation inflammasomes closely follows animal models. Currently there is no method to rescue photoreceptors cells from the mediated cell death pathway despite surgical intervention. Thus, current visual prognosis and prevention of further photoreceptor loss due to a RD is likely dependent on the time of surgical intervention before further detachment and further cell death can occur. As such, the purpose of this current study is to confirm the presence of inflammasome activation as well as the synthesis of its products, IL-1β and IL-18, in patients with rhegmatogenous retinal detachments. Both inflammasomes and its products IL-1β and IL-18 may be involved in cell pyroptosis, a programmed cell death distinct from apoptosis. Due to a lack of treatment for the rescue of photoreceptor cells from cell death after a retinal detachment, this study can provide novel strategies to inhibit cell death.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| RD treated with vitrectomy | – | Procedure: Pars plana vitrectomyVitreous fluid from retinal detachment treated with pars plana vitrectomy |
| RD treated with external drainage | – | Procedure: External drainageSubretinal fluid from retinal detachment treated with external drainage. |
| Macular holes treated with vitrectomy | – | Procedure: Pars plana vitrectomyVitreous fluid from patients treated for macular hole |
| ERM treated with vitrectomy | – | Procedure: Pars plana vitrectomyVitreous fluid from patients treated for epiretinal membrane |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with retinal detachment, macular hole, or epiretinal membrane.
Key inclusion criteria (5 listed)
- Patient of the Wills Eye Hospital Retina service and Mid-Atlantic Retina offices.
- Volunteer patients age 18 years and older.
- Healthy enough to participate in the study.
- Willing and able to consent to participation in the study.
- Diagnosis of rhegmatogenous retinal detachment treated with external drainage of subretainl fluid, rhegmatogenous retinal detachment treated with pars plana vitrectomy, or full thickness macular hole treated with pars plana vitrectomy
Key exclusion criteria (4 listed)
- Presence of tractional retinal detachment
- History of trauma
- Presence of proliferative vitreoretinopathy
- History of prior retinal detachment repair or any prior retina surgery or laser treatment e. Any preexisting retinal disease (including diabetic retinopathy, age related macular degeneration, retinal vein or artery occlusion, other retinal vascular disease, inherited retinal degeneration, uveitis)
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 |
|---|---|---|
| Pars plana vitrectomyStandard of care treatment for retinal detachment, macular hole, or epiretinal membrane. | Procedure or surgery | ERM treated with vitrectomy, Macular holes treated with vitrectomy, RD treated with vitrectomy |
| External drainageStandard of care treatment for retinal detachment. | Procedure or surgery | RD treated with external drainage |
Primary outcome
Presence of inflammasomes and their active products
Time frame: Day of surgery
Presence of inflammasomes and their active products in patients with retinal detachment treated with vitrectomy or external drainage, macular holes treated with vitrectomy, and epiretinal membranes treated with vitrectomy
1 secondary outcome
Difference in inflammasome levels among samples
Time frame: Day of surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Background: PubMed 23994436Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG. Photoreceptor cell death and rescue in retinal detachment and degenerations. Prog Retin Eye Res. 2013 Nov;37:114-40. doi: 10.1016/j.preteyeres.2013.08.001. Epub 2013 Aug 28.
- Background: PubMed 25906154Kataoka K, Matsumoto H, Kaneko H, Notomi S, Takeuchi K, Sweigard JH, Atik A, Murakami Y, Connor KM, Terasaki H, Miller JW, Vavvas DG. Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal detachment-induced photoreceptor cell death. Cell Death Dis. 2015 Apr 23;6(4):e1731. doi: 10.1038/cddis.2015.73.
- Individual participant dataSharing planned: Undecided. manuscript under development
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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.
Allen C Ho, MD principal investigator
MidAtlantic Retina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Retinal Detachment and Full Thickness Macular Hole, run by Allen C. Ho, MD 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 5 inclusion and 4 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 17 Aug 2018. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Presence of inflammasomes and their active products (time frame: Day of surgery). 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 NCT03332758, which also lists 2 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 17 Aug 2018.