Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inflammasomes in Cell Death in FTMH, ERM, and RRD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03332758
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : August 17, 2018
Sponsor:
Collaborator:
Mid Atlantic Retina
Information provided by (Responsible Party):
Allen C. Ho, MD, Wills Eye

Brief 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 established assays.

Condition or disease Intervention/treatment
Retinal Detachment Full Thickness Macular Hole Epiretinal Membrane Procedure: Pars plana vitrectomy Procedure: External drainage

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 41 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Inflammasomes in Cell Death in Macular Hole, Epiretinal Membrane, and Rhegmatogenous Retinal Detachment
Actual Study Start Date : September 8, 2017
Actual Primary Completion Date : April 10, 2018
Actual Study Completion Date : May 1, 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
RD treated with vitrectomy
Vitreous fluid from retinal detachment treated with pars plana vitrectomy
Procedure: Pars plana vitrectomy
Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

RD treated with external drainage
Subretinal fluid from retinal detachment treated with external drainage.
Procedure: External drainage
Standard of care treatment for retinal detachment.

Macular holes treated with vitrectomy
Vitreous fluid from patients treated for macular hole
Procedure: Pars plana vitrectomy
Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

ERM treated with vitrectomy
Vitreous fluid from patients treated for epiretinal membrane
Procedure: Pars plana vitrectomy
Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Difference in inflammasome levels among samples [ Time Frame: Day of surgery ]
    Difference in inflammasome pathway activation between retinal detachment, macular hole, and epiretinal membrane samples


Biospecimen Retention:   Samples With DNA
Vitreous fluid and subretinal fluid


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adults with retinal detachment, macular hole, or epiretinal membrane.
Criteria

Inclusion Criteria:

  1. Patient of the Wills Eye Hospital Retina service and Mid-Atlantic Retina offices.
  2. Volunteer patients age 18 years and older.
  3. Healthy enough to participate in the study.
  4. Willing and able to consent to participation in the study.
  5. 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

Exclusion Criteria:

  1. Presence of tractional retinal detachment
  2. History of trauma
  3. Presence of proliferative vitreoretinopathy
  4. 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332758


Locations
Layout table for location information
United States, Pennsylvania
MidAtlantic Retina-Wills Eye Hospital
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Allen C. Ho, MD
Mid Atlantic Retina
Investigators
Layout table for investigator information
Principal Investigator: Allen C Ho, MD MidAtlantic Retina

Publications:
Layout table for additonal information
Responsible Party: Allen C. Ho, MD, Principal Investigator, Wills Eye
ClinicalTrials.gov Identifier: NCT03332758     History of Changes
Other Study ID Numbers: 17-660E
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: manuscript under development

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Allen C. Ho, MD, Wills Eye:
retinal detachment
inflammasome
macular hole

Additional relevant MeSH terms:
Layout table for MeSH terms
Retinal Detachment
Retinal Perforations
Epiretinal Membrane
Retinal Diseases
Eye Diseases