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Trial registered on ANZCTR


Registration number
ACTRN12618000079246
Ethics application status
Approved
Date submitted
8/12/2017
Date registered
19/01/2018
Date last updated
27/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Influence of Serum and Aqueous Cytokine Concentrations on the Efficacy of Intravitreal Ranibizumab for the Treatment of Diabetic Macular Oedema
Scientific title
The Influence of Serum and Aqueous Cytokine Concentrations on the Efficacy of Intravitreal Ranibizumab for the Treatment of Diabetic Macular Oedema
Secondary ID [1] 293564 0
Nil
Universal Trial Number (UTN)
U1111-1172-6184
Trial acronym
DME Cytokine Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Oedema 305797 0
Condition category
Condition code
Eye 305015 305015 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 305016 305016 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible participants will receive treatment with ranibizumab 0.5mg in 50 microliters for intravitreal injection.
All participants will undergo three consecutive, monthly injections, followed by an as required dosing schedule (PRN) for the 12 month duration of the trial.
Only dosing schedule is adjusted on a PRN basis, not the dosing ranges. Dosing ranges will remain the same throughout the study duration.
Dosing schedule is determined by the following:
As per the RESTORE study, all participants will undergo three consecutive, monthly injections, followed by an as required dosing schedule (PRN). After month 2 (week 8), at monthly study visits, the need for further intravitreal treatment will be assessed based on BCVA and OCT assessment.
Monthly ranibizumab injections would be suspended when:
• No (further) BCVA improvement is attributed in the opinion of the investigator to
treatment with intravitreal injection at the 2 last consecutive visits,
• BCVA letter score >84 (6/6) at the last 2 consecutive follow up visits
Monthly ranibizumab injections would be reinitiated when:
• Decrease in BCVA due to DME progression in the opinion of the masked study team
Monthly ranibizumab will be continued if there is continued BCVA improvement or if in the treating physicians’ opinion, disease stability has not been achieved.
Intervention code [1] 299809 0
Treatment: Drugs
Comparator / control treatment
All patients will receive Intravitreal Ranibizumab, the influence of plasma and aqueous cytokine concentrations on the efficacy of the intervention will be measured.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304181 0
To assess if aqueous and serum cytokine concentrations of angiogenic/ inflammatory cytokines including IL-10 and IL-17 correlate with the change in mean best-corrected visual acuity from baseline to 12 months.
Best-corrected visual acuity will be assessed on a LogMAR chart.
Timepoint [1] 304181 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [1] 341147 0
To assess if aqueous and serum cytokine concentrations correlate with the number of ranibizumab injections given by 12 months
Timepoint [1] 341147 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [2] 341148 0
To assess if aqueous and serum cytokine concentrations correlate with the likelihood of recurrent diabetic macular oedema after cessation of ranibizumab
Optical coherence tomography (OCT) and a clinical evaluation including a dilated fundus examination examined with an indirect lens performed by the Principal/Sub investigators.
Other clinical assessments can also be performed if necessary, including Fluorescein Angiography and fundus photography.
Timepoint [2] 341148 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [3] 341149 0
To assess if aqueous and serum cytokine concentrations correlate with the length of time from baseline to vision stabilization, leading to cessation of ranibizumab
Best-corrected visual acuity is measured at all study visits using Retroilluminated Chart R, 1 and 2 from Ferris-Bailey LOGMAR distance visual acuity chart set, standard lighting, and procedures. Best correction is determined by careful refraction at that visit according to the standard protocol for Refraction.
Refraction and visual acuity measurements will be performed for all patients by a trained vision examiner.
Timepoint [3] 341149 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [4] 341150 0
To assess if aqueous and serum cytokine concentrations correlate with the mean change in macular thickness from baseline to 12 months
Optical coherence tomography (OCT) and a clinical evaluation including a dilated fundus examination examined with an indirect lens performed by the Principal/Sub investigators.
Other clinical assessments can also be performed if necessary, including Fluorescein Angiography and fundus photography.
Timepoint [4] 341150 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [5] 341151 0
To assess if aqueous and serum cytokine concentrations correlate with the need for rescue therapy
Aqueous and serum cytokine concentration values will be assessed at Baseline visit, month 2 and month 12 visits. These values will be assessed as to whether they reveal the prediction outcomes of the patients DME status and whether there is a correlation in the outcomes of the aqueous and serum cytokine concentration values with the patients who required rescue therapy during the study- if there is a correlation proven than it can be a potential predictor of patients who require rescue therapy in the future.
The MILLIPLEX MAP® is based on Luminex xMAP® technology. The kit is able to assess for 32 different cytokines and includes: EGF, EPO, IL-10, IL-17, IL-1a, IL-6, IL-8, MCP-1, IFN, TNFa, MIP-1a, interferon-inducible 10-kDa protein (IP-10) and VEGF that we are interested in assessing. Analysis of Ang2 will utilise the ELISA kit.
Timepoint [5] 341151 0
12 months after first ranibizumab injection or the baseline visit.
Secondary outcome [6] 341152 0
To assess if the change in aqueous and serum cytokine concentrations from baseline to month 2 correlates with change in central macular thickness from baseline to 12 months
Optical coherence tomography (OCT) and a clinical evaluation including a dilated fundus examination examined with an indirect lens performed by the Principal/Sub investigators.
Other clinical assessments can also be performed if necessary, including Fluorescein Angiography and fundus photography.
Timepoint [6] 341152 0
12 months after first ranibizumab injection or the baseline visit.

Eligibility
Key inclusion criteria
(i) Age >18 years
(ii) Centre involving diabetic macular oedema that in the opinion of the investigator, would not benefit from macular laser treatment (eg diffuse leak from the capillary bed, disruption of the foveal avascular zone or perifoveal capillary dropout) as determined by fluorescein angiography
(iii) Best-corrected visual acuity (BCVA) of 17-70 letters (6/12 –6/120)
(iv) Central macular thickness of >300 microns as measured by Heidelberg Optical coherence tomography.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systemic
(v) Uncontrolled blood pressure (>180 mmHg, systolic and 110 mmHg, diastolic)
(vi) Chronic renal failure
(vii) Major surgery within one month of study
(viii) Previous systemic anti-VEGF treatment
(ix) Women of childbearing potential not using adequate contraception and women who are breast feeding
(x) Intercurrent severe disease such as septicaemia

Ocular
(i) Glaucoma which is uncontrolled or is controlled but with glaucomatous visual field defects
(ii) Past history of severe steroid response with IOP > 35 mmHg following steroid treatment
(iii) Loss of vision due to other causes (e.g. age-related macular degeneration, myopic macular degeneration)
(iv) VA of <6/60 in the fellow eye
(v) Argon laser photocoagulation within 3 months of study entry
(vi) Previous intraocular surgery (within 6 months)
(vii) Prior use of intravitreal anti-VEGF agents (within 3 months) or corticosteroids (within 6 months)
(viii) Stroke or myocardial infarction less than 3 months prior to screening.
(ix) Any active periocular or ocular infection or inflammation at screening or baseline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2018
Actual
Date of last participant enrolment
Anticipated
1/07/2019
Actual
Date of last data collection
Anticipated
1/07/2020
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9515 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 18262 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 298178 0
Charities/Societies/Foundations
Name [1] 298178 0
Juvenile Diabetes Research Foundation
Country [1] 298178 0
Australia
Primary sponsor type
Other
Name
The Centre for Eye Research Australia
Address
Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 297276 0
None
Name [1] 297276 0
Nil
Address [1] 297276 0
Nil
Country [1] 297276 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299193 0
The Royal Victorian Eye and Ear Hospital Human Research and Ethics Committee
Ethics committee address [1] 299193 0
Ethics committee country [1] 299193 0
Australia
Date submitted for ethics approval [1] 299193 0
09/08/2017
Approval date [1] 299193 0
16/10/2017
Ethics approval number [1] 299193 0
13/1123H

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79606 0
Dr Sanjeewa Wickremasinghe
Address 79606 0
Centre for Eye Research Australia
Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country 79606 0
Australia
Phone 79606 0
+61 3 9929 8076
Fax 79606 0
+61 3 9929 8030
Email 79606 0
sanj.wickremasinghe@eyeandear.org.au
Contact person for public queries
Name 79607 0
Sutha Sanmugasundram
Address 79607 0
Centre for Eye Research Australia
Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country 79607 0
Australia
Phone 79607 0
+61 3 9929 8076
Fax 79607 0
+61 3 9929 8030
Email 79607 0
Sans@unimelb.edu.au
Contact person for scientific queries
Name 79608 0
Sanjeewa Wickremasinghe
Address 79608 0
Centre for Eye Research Australia
Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002
Country 79608 0
Australia
Phone 79608 0
+61 3 9929 8076
Fax 79608 0
+61 3 9929 8030
Email 79608 0
sanj.wickremasinghe@eyeandear.org.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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