InflammationPhase 1ProstaglandinNCT01609881
The Role of Prostaglandins in the Progression of Diabetic Retinopathy
A Phase 1 study testing Acuvail in people with Inflammation, run by Vanderbilt University at 1 site in United States.
Trial summary
Objective of the research study: 1. To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Inflammation
- What is being tested?
- Acuvail
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to 19 Oct 2016
- Phase
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged 18 years or older who present for vitrectomy surgery for any indication.
- Diabetic and non-diabetic patients will be included.
Who cannot join
- Patients under the age of 18 years of age.
- Pregnant women.
- Patients with a history of vitrectomy surgery.
- Current topical, periocular, intraocular or systemic corticosteroid use
- Co-existent macular, retinovascular or ocular inflammatory disease (age-related macular degeneration, retinal venous occlusive disease, uveitis, etc.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Eye Institute
Nashville, Tennessee, 37232-8808
About this study
Official title: The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)
Objective of the research study:
- To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2)
- To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy
- To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients
- To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy.
Read more
Research hypothesis
- Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2
- Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls
- Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
Read the detailed description
Patients who require vitrectomy for any indication and those meeting the inclusion/exclusion criteria will be included. Patients will be consented to participate in the study and for surgery.
Nondiabetic patients will be included in one of two groups. Twenty will receive topical ketorolac (Acuvail®) preoperatively for 3 days and then samples will be taken at the time of surgery. Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels (to be compared to diabetic patients). This group will not receive preoperative ketorolac (Acuvail®).
Diabetic patients will be included in one of two groups. Twenty patients will have intraocular prostaglandin and cytokine levels measured. Twenty other patients will be in the interventional group to determine if topical ketorolac (Acuvail®) can successfully lower intraocular prostaglandin and inflammatory cytokine levels.
In all cases, patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition. For this study, undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy. These samples will be stored, analyzed and frozen.
Samples will be tested for prostaglandin levels, in addition to other inflammatory cytokines, and ketorolac levels.
Three days of Acuvail® given four times per day was chosen, as previous studies have shown that one dose of ketorolac 0.4% achieves a peak aqueous concentration of 57.5 ng/mL,1 and that 12 doses over two days achieves an aqueous concentration of 1079 ng/mL.2 Both values are well above the IC50 for COX-1 (5.3 to 7.5 ng/mL) and COX-2 (33.9-45.2 ng/mL). The upper end of this dosing spectrum was chosen, as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2. This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively.3
- Conditions
- Inflammation
- Being tested
- Acuvail, Placebo
- Keywords
- Inflammation
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcuvailDrug
Also called Ketorolac 0.45%
Dosing of drug 3 days prior to surgery
PlaceboOther
Also called tears
Artificial tears qid for 3 days preoperatively
| Study group | Role | What they receive |
|---|---|---|
| Acuvail | Other | Acuvail as preventive for inflammation and possible decrease or prevent diabetic retinopathy. The study has four arms - diabetic ketorolac, diabetic control, normal eyes ketorolac, normal eyes control. patients are randomized to ketorolac or control. Receives: Drug: Acuvail |
| Placebo | Placebo comparator | Placebo using artificial tear drops Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
Measured: 3 days
Secondary outcomes (2)
Primary Outcome
The primary outcomes include drug and prostaglandin concentrations on the anterior chamber and vitreous.
Measured: 7 days
Secondary Outcome
The secondary outcome will include cytokine levels in the vitreous.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2012 (estimated)
- Study startMar 2012
- Primary completion19 Oct 2016
- Study completion19 Oct 2016
Why it stopped: Due to lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stephen J. Kim, MD, Vanderbilt University
- Investigators
- Stephen J Kim, MD, Principal investigator, Vanderbilt Eye Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01609881
- Sponsor's protocol ID
- 12022
- Acronym
- Prostaglandin
- Status last verified
- Feb 2017
- First submitted
- 27 Mar 2012
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Schoenberger SD, Kim SJ, Shah R, Sheng J, Cherney E. Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy. JAMA Ophthalmol. 2014 Jan;132(1):32-7. doi: 10.1001/jamaophthalmol.2013.6203.
PubMed 24336915Schoenberger SD, Kim SJ, Sheng J, Calcutt MW. Reduction of vitreous prostaglandin E2 levels after topical administration of ketorolac 0.45%. JAMA Ophthalmol. 2014 Feb;132(2):150-4. doi: 10.1001/jamaophthalmol.2013.5692.
PubMed 24264034Schoenberger SD, Kim SJ, Sheng J, Rezaei KA, Lalezary M, Cherney E. Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines. Invest Ophthalmol Vis Sci. 2012 Aug 27;53(9):5906-11. doi: 10.1167/iovs.12-10410.
PubMed 22871833
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)
- ClinicalTrials.gov ID
- NCT01609881
- Acronym / sponsor ID
- Prostaglandin / 12022
- Conditions
- Inflammation
- Keywords
- Inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Mar 2012 (actual)
- Primary completion
- 19 Oct 2016 (actual)
- Study completion
- 19 Oct 2016 (actual)
- First posted
- 1 Jun 2012 (estimated)
- 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.
Objective of the research study:
- To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2)
- To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy
- To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients
- To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy.
Research hypothesis
- Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2
- Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls
- Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
Detailed description
Patients who require vitrectomy for any indication and those meeting the inclusion/exclusion criteria will be included. Patients will be consented to participate in the study and for surgery.
Nondiabetic patients will be included in one of two groups. Twenty will receive topical ketorolac (Acuvail®) preoperatively for 3 days and then samples will be taken at the time of surgery. Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels (to be compared to diabetic patients). This group will not receive preoperative ketorolac (Acuvail®).
Diabetic patients will be included in one of two groups. Twenty patients will have intraocular prostaglandin and cytokine levels measured. Twenty other patients will be in the interventional group to determine if topical ketorolac (Acuvail®) can successfully lower intraocular prostaglandin and inflammatory cytokine levels.
In all cases, patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition. For this study, undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy. These samples will be stored, analyzed and frozen.
Samples will be tested for prostaglandin levels, in addition to other inflammatory cytokines, and ketorolac levels.
Three days of Acuvail® given four times per day was chosen, as previous studies have shown that one dose of ketorolac 0.4% achieves a peak aqueous concentration of 57.5 ng/mL,1 and that 12 doses over two days achieves an aqueous concentration of 1079 ng/mL.2 Both values are well above the IC50 for COX-1 (5.3 to 7.5 ng/mL) and COX-2 (33.9-45.2 ng/mL). The upper end of this dosing spectrum was chosen, as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2. This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively.3
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acuvail | Other | Drug: AcuvailAcuvail as preventive for inflammation and possible decrease or prevent diabetic retinopathy. The study has four arms - diabetic ketorolac, diabetic control, normal eyes ketorolac, normal eyes control. patients are randomized to ketorolac or control. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo using artificial tear drops |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients aged 18 years or older who present for vitrectomy surgery for any indication.
- Diabetic and non-diabetic patients will be included.
Key exclusion criteria (5 listed)
- Patients under the age of 18 years of age.
- Pregnant women.
- Patients with a history of vitrectomy surgery.
- Current topical, periocular, intraocular or systemic corticosteroid use
- Co-existent macular, retinovascular or ocular inflammatory disease (age-related macular degeneration, retinal venous occlusive disease, uveitis, etc.)
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 |
|---|---|---|
| AcuvailAlso: Ketorolac 0.45%Dosing of drug 3 days prior to surgery | Drug | Acuvail |
| PlaceboAlso: tearsArtificial tears qid for 3 days preoperatively | Other | Placebo |
Primary outcome
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
Time frame: 3 days
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
2 secondary outcomes
Primary Outcome
Time frame: 7 days
Secondary Outcome
Time frame: 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Derived from this study: PubMed 24336915Schoenberger SD, Kim SJ, Shah R, Sheng J, Cherney E. Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy. JAMA Ophthalmol. 2014 Jan;132(1):32-7. doi: 10.1001/jamaophthalmol.2013.6203.
- Derived from this study: PubMed 24264034Schoenberger SD, Kim SJ, Sheng J, Calcutt MW. Reduction of vitreous prostaglandin E2 levels after topical administration of ketorolac 0.45%. JAMA Ophthalmol. 2014 Feb;132(2):150-4. doi: 10.1001/jamaophthalmol.2013.5692.
- Derived from this study: PubMed 22871833Schoenberger SD, Kim SJ, Sheng J, Rezaei KA, Lalezary M, Cherney E. Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines. Invest Ophthalmol Vis Sci. 2012 Aug 27;53(9):5906-11. doi: 10.1167/iovs.12-10410.
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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.
Stephen J Kim, MD principal investigator
Vanderbilt Eye Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Acuvail in people with Inflammation, run by Vanderbilt University 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 2 inclusion and 5 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: withdrawn, as of the sponsor's last update on 23 Feb 2017. 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 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.
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 was withdrawn before enrolling participants, so there are no results.
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?
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail (time frame: 3 days). 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 NCT01609881, 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 23 Feb 2017.