NCT04980144

Brief Summary

Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal glands function. While it has been observed that 0.1 percent hyaluronate (HA) in artificial tears promotes corneal re-epithelium and improves corneal healing.This prospective, open label pilot study will include 60 eyes of 30 diabetic patients diagnosed with DED and will be randomly assigned to either DQS (n=30 eyes) or ATD group (n=30 eyes). Participants in the DQS group will receive 3% Diquafosol ophthalmic solution, while HA group will receive 0.1% Sodium hyaluronate artificial tears. The dosage for both drugs will be one drop, six times per day for 4 weeks. Tear film lipid layer (TFLL), non-invasive breakup time (NITBUT), corneoconjunctival staining score (CS), meibum gland (MG), conjunctival hyperemia (RS score), ocular surface disease index (OSDI) will be assessed and compared at baseline, day-14, and day-28.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
101

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Mar 2023

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 19, 2021

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 28, 2021

Completed
1.6 years until next milestone

Study Start

First participant enrolled

March 3, 2023

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2023

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2023

Completed
Last Updated

January 12, 2023

Status Verified

January 1, 2023

Enrollment Period

6 months

First QC Date

July 19, 2021

Last Update Submit

January 10, 2023

Conditions

Diabetic Eye Problems

Keywords

Dry eyeDiquafosolHyaluronateDiabetic dry eye

Outcome Measures

Primary Outcomes (3)

  • Non-invasive tear break-up time

    Changes in non-invasive initial tear film breaking time will be assessed using the Keratograph 5M (Oculus, Germany) topographer. Three sequentially readings will be captured, and the median value will be included in the final analysis. The median value will be recorded. * Changes at 4-weeks and 8-weeks will be compare with baseline measurements. * Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined

    Day-0 (baseline), 4-weeks, 8-weeks

  • Tear Film Lipid Layer

    Tear Film Lipid Layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan). * Changes at 4-weeks and 8-weeks will be compare with baseline measurements. * Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined

    Day-0 (baseline), 4-weeks, 8-weeks

  • OSDI Score

    Chinese translated, and validated OSDI (Allergan Inc, Irvine, USA) version will beused to assess and quantify DE symptom. The 12 items of the questionnaire can be tabulated into a score that ranges from 0 (no symptoms) to 100 (severe symptoms) points * Changes at 4-weeks and 8-weeks will be compare with baseline measurements. * Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined

    Day-0 (baseline), 4-weeks, 8-weeks

Secondary Outcomes (4)

  • Conjunctival hyperemia (RS score)

    Day-0 (baseline), 4-weeks, 8-weeks

  • Quality of meibum grade

    Day-0 (baseline), 4-weeks, 8-weeks

  • Expressibility of meibum grade

    Day-0 (baseline), 4-weeks, 8-weeks

  • Conjunctivocorneal epithelial staining grade

    Day-0 (baseline), 4-weeks, 8-weeks

Study Arms (2)

DQS group

EXPERIMENTAL

Participants in DQS group will be administered one drop of 3% DQS (Diquas, Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times per day for 8 weeks.

Drug: 3% Diquafosol tetrasodium

HA group

ACTIVE COMPARATOR

Participants in HA group will be administered one drop of 0.1% Sodium hyaluronate artificial tears (preservative free) six times per day for 8 weeks.

Drug: 0.1% hyaluronate

Interventions

3% Diquafosol tetrasodiumDRUG

3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in diabetic dry eye symptoms

Also known as: Diquas
DQS group
0.1% hyaluronateDRUG

0.1% hyaluronate eye drops will be used to assess its usefulness in diabetic dry eye symptoms and compared to 3% Diquafosol tetrasodium eye drops.

Also known as: Artificial tears
HA group

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • Clinical diagnosed and confirmed with type 2 diabetes for one year or more
  • Able and willing to comply with the treatment/follow-up schedule
  • Bilateral signs and symptoms of dry eye disease

You may not qualify if:

  • Participants with systemic immune-mediated illnesses, such as secondary Sjögren's syndrome or graft-versus-host disease
  • Patients using topical medication(s) for the treatment of ocular disorders such as glaucoma or allergic conjunctivitis were excluded from the study.
  • Previous ocular surgery or trauma
  • month history of blepharal and periorbital skin disease or allergies
  • Severe dry eyes with corneal epithelial defect
  • Limbic keratitis
  • Pterygium
  • Corneal neovascularization
  • Glaucoma
  • Breastfeeding
  • Rheumatic immune systemic diseases
  • Herpes zoster infection
  • Pregnant women
  • Allergic to fluorescein
  • Contact lens wearers

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

He Eye Hospital

Shenyang, Liaoning, 110001, China

Location

Related Publications (27)

  • Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun 3;389(10085):2239-2251. doi: 10.1016/S0140-6736(17)30058-2. Epub 2017 Feb 10.

    PMID: 28190580RESULT

  • Weisman A, Fazli GS, Johns A, Booth GL. Evolving Trends in the Epidemiology, Risk Factors, and Prevention of Type 2 Diabetes: A Review. Can J Cardiol. 2018 May;34(5):552-564. doi: 10.1016/j.cjca.2018.03.002. Epub 2018 Mar 13.

    PMID: 29731019RESULT

  • Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019 Nov;157:107843. doi: 10.1016/j.diabres.2019.107843. Epub 2019 Sep 10.

    PMID: 31518657RESULT

  • Abdelkader H, Patel DV, McGhee CNj, Alany RG. New therapeutic approaches in the treatment of diabetic keratopathy: a review. Clin Exp Ophthalmol. 2011 Apr;39(3):259-70. doi: 10.1111/j.1442-9071.2010.02435.x. Epub 2011 Apr 4.

    PMID: 20973888RESULT

  • Vieira-Potter VJ, Karamichos D, Lee DJ. Ocular Complications of Diabetes and Therapeutic Approaches. Biomed Res Int. 2016;2016:3801570. doi: 10.1155/2016/3801570. Epub 2016 Mar 28.

    PMID: 27119078RESULT

  • El-Agamy A, Alsubaie S. Corneal endothelium and central corneal thickness changes in type 2 diabetes mellitus. Clin Ophthalmol. 2017 Mar 2;11:481-486. doi: 10.2147/OPTH.S126217. eCollection 2017.

    PMID: 28280298RESULT

  • Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye (Lond). 2006 Mar;20(3):315-8. doi: 10.1038/sj.eye.6701868.

    PMID: 15832184RESULT

  • Inoue K, Okugawa K, Amano S, Oshika T, Takamura E, Egami F, Umizu G, Aikawa K, Kato S. Blinking and superficial punctate keratopathy in patients with diabetes mellitus. Eye (Lond). 2005 Apr;19(4):418-21. doi: 10.1038/sj.eye.6701497.

    PMID: 15286669RESULT

  • Shih KC, Lam KS, Tong L. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutr Diabetes. 2017 Mar 20;7(3):e251. doi: 10.1038/nutd.2017.4.

    PMID: 28319106RESULT

  • Murphy PJ, Patel S, Kong N, Ryder RE, Marshall J. Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1737-42. doi: 10.1167/iovs.03-0689.

    PMID: 15161834RESULT

  • Dogru M, Katakami C, Inoue M. Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus. Ophthalmology. 2001 Mar;108(3):586-92. doi: 10.1016/s0161-6420(00)00599-6.

    PMID: 11237914RESULT

  • Sagdik HM, Ugurbas SH, Can M, Tetikoglu M, Ugurbas E, Ugurbas SC, Alpay A, Ucar F. Tear film osmolarity in patients with diabetes mellitus. Ophthalmic Res. 2013;50(1):1-5. doi: 10.1159/000345770. Epub 2013 Feb 22.

    PMID: 23445780RESULT

  • Barbosa FL, Xiao Y, Bian F, Coursey TG, Ko BY, Clevers H, de Paiva CS, Pflugfelder SC. Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease. Int J Mol Sci. 2017 May 5;18(5):978. doi: 10.3390/ijms18050978.

    PMID: 28475124RESULT

  • Marko CK, Menon BB, Chen G, Whitsett JA, Clevers H, Gipson IK. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye. Am J Pathol. 2013 Jul;183(1):35-48. doi: 10.1016/j.ajpath.2013.03.017. Epub 2013 May 10.

    PMID: 23665202RESULT

  • Park Y, Song JS, Choi CY, Yoon KC, Lee HK, Kim HS. A Randomized Multicenter Study Comparing 0.1%, 0.15%, and 0.3% Sodium Hyaluronate with 0.05% Cyclosporine in the Treatment of Dry Eye. J Ocul Pharmacol Ther. 2017 Mar;33(2):66-72. doi: 10.1089/jop.2016.0086. Epub 2016 Dec 8.

    PMID: 27929721RESULT

  • Jeon HS, Hyon JY. The Efficacy of Diquafosol Ophthalmic Solution in Non-Sjogren and Sjogren Syndrome Dry Eye Patients Unresponsive to Artificial Tear. J Ocul Pharmacol Ther. 2016 Sep;32(7):463-8. doi: 10.1089/jop.2015.0081. Epub 2016 Jun 13.

    PMID: 27294831RESULT

  • Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998 Sep;67(3):341-6. doi: 10.1006/exer.1998.0520.

    PMID: 9778415RESULT

  • Dota A, Sakamoto A, Nagano T, Murakami T, Matsugi T. Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats. Clin Ophthalmol. 2020 Apr 1;14:1019-1024. doi: 10.2147/OPTH.S242764. eCollection 2020.

    PMID: 32280196RESULT

  • Kulkarni AA, Trousdale MD, Stevenson D, Gukasyan HJ, Shiue MH, Kim KJ, Read RW, Lee VH. Nucleotide-induced restoration of conjunctival chloride and fluid secretion in adenovirus type 5-infected pigmented rabbit eyes. J Pharmacol Exp Ther. 2003 Jun;305(3):1206-11. doi: 10.1124/jpet.103.049221. Epub 2003 Mar 20.

    PMID: 12649304RESULT

  • Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003 Jul;77(1):77-84. doi: 10.1016/s0014-4835(03)00068-x.

    PMID: 12823990RESULT

  • Tanioka H, Kuriki Y, Sakamoto A, Katsuta O, Kawazu K, Nakamura M. Expression of the P2Y(2) receptor on the rat ocular surface during a 1-year rearing period. Jpn J Ophthalmol. 2014 Nov;58(6):515-21. doi: 10.1007/s10384-014-0342-4. Epub 2014 Sep 2.

    PMID: 25179431RESULT

  • Yuko, T.S.; NAKAMURA, M. Stimulatory Effect of Diquafosol Tetrasodium on the Expression of Membrane-Binding Mucin Genes in Cultured Human Corneal Epithelial Cells. Journal of the eye 2011, 28, 425-429.

    RESULT

  • Kaido M, Kawashima M, Shigeno Y, Yamada Y, Tsubota K. Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye. Adv Ther. 2018 May;35(5):697-706. doi: 10.1007/s12325-018-0685-1. Epub 2018 Apr 18.

    PMID: 29671255RESULT

  • Ji YW, Kim HM, Ryu SY, Oh JW, Yeo A, Choi CY, Kim MJ, Song JS, Kim HS, Seo KY, Kim KP, Lee HK. Changes in Human Tear Proteome Following Topical Treatment of Dry Eye Disease: Cyclosporine A Versus Diquafosol Tetrasodium. Invest Ophthalmol Vis Sci. 2019 Dec 2;60(15):5035-5044. doi: 10.1167/iovs.19-27872.

    PMID: 31800960RESULT

  • Amano S, Inoue K. Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction. Clin Ophthalmol. 2017 Sep 14;11:1677-1682. doi: 10.2147/OPTH.S148167. eCollection 2017.

    PMID: 29075094RESULT

  • Ohashi Y, Munesue M, Shimazaki J, Takamura E, Yokoi N, Watanabe H, Nomura A, Shimada F. Long-Term Safety and Effectiveness of Diquafosol for the Treatment of Dry Eye in a Real-World Setting: A Prospective Observational Study. Adv Ther. 2020 Feb;37(2):707-717. doi: 10.1007/s12325-019-01188-x. Epub 2019 Dec 13.

    PMID: 31834617RESULT

  • Zhang Q, Zhang H, Qin G, Wu Y, Song Y, Yang L, Yu S, He X, Moore JE, Moutari S, Palme C, Xu L, He W, Pazo EE. Impact of Diquafosol Ophthalmic Solution on Tear Film and Dry Eye Symptom in Type 2 Diabetic Dry Eye: A Pilot Study. J Ocul Pharmacol Ther. 2022 Mar;38(2):133-140. doi: 10.1089/jop.2021.0083. Epub 2022 Jan 19.

    PMID: 35049373DERIVED

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

Lubricant Eye Drops

Condition Hierarchy (Ancestors)

Lacrimal Apparatus DiseasesEye Diseases

Intervention Hierarchy (Ancestors)

Ophthalmic SolutionsPharmaceutical SolutionsSolutionsPharmaceutical PreparationsTherapeutic UsesPharmacologic ActionsChemical Actions and UsesLubricantsSpecialty Uses of Chemicals

Study Officials

  • Emmanuel Eric Pazo

    He Eye Hospital, Shenyang, China

    STUDY CHAIR

Central Study Contacts

Emmanuel Eric E Pazo, PhD

CONTACT

0086-18612782131ericpazo@outlook.com

Hongda Zhang, MD

CONTACT

0086-13840298177596949091@qq.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Masked examiner for all clinical assessments will not involved in the data collection or group allocation procedure for this research. The investigator will not be aware of the two groups.
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Model Details: Prospective, comparative pilot study
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 19, 2021

First Posted

July 28, 2021

Study Start

March 3, 2023

Primary Completion

August 31, 2023

Study Completion

November 1, 2023

Last Updated

January 12, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)