Ectopic activation of TRPM8 with a newly-developed agonist relieves dry-eye symptoms

ISRCTN	ISRCTN13359367
DOI	https://doi.org/10.1186/ISRCTN13359367
Protocol serial number	N/A
Sponsor	Chonnam National University Medical School and Hospital
Funder	Investigator initiated and funded

Submission date: 01/09/2015
Registration date: 02/09/2015
Last edited: 23/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Dry eye disease occurs when the eyes do not make enough tears or the tears evaporate too quickly, leading to the eyes drying out and becoming inflamed (red and swollen) and irritated. Our aim is to study the effect of daily topical administration of a drug called a TRPM8 agonist in patients with mild to moderate dry eye disease.

Who can participate?
Patients with mild to moderate dry eye.

What does the study involve?
Patients are randomly allocated to be treated with either TRPM8 agonist dissolved in distilled water, or distilled water only. Study medications will be topically applied to the upper eyelid 4 times daily (every 6 hours) for 2 weeks with using a stick filled with TRPM8 agonist or distilled water only.

What are the possible benefits and risks of participating?
The treatment may relieve dry eye related eye symptoms. There are no risks involved in this study.

Where is the study run from?
Department of Ophthalmology, Chonnam National University Medical School and Hospital (South Korea).

When is the study starting and how long is it expected to run for?
From January 2015 to August 2015.

Who is funding the study?
Investigator initiated and funded (South Korea).

Who is the main contact?
Pf. Kyung Chul Yoon
kcyoon@jnu.ac.kr

Contact information

Prof Kyung Chul Yoon
Scientific

Department of Ophthalmology
Chonnam National University Medical School and Hospital
42 Jebong-ro
Dong-gu
Gwangju
501-757
Gwangju
KS0008
Korea, South

ORCID ID	0000-0002-2788-1851

Study information

Primary study design	Interventional
Study design	Single-center randomized double-masked vehicle-controlled study
Secondary study design	Randomised controlled trial
Scientific title	Effect of daily topical administration of TRPM8 agonist in patients with mild to moderate dry eye disease: a single-center randomized double-masked vehicle-controlled study
Study objectives	Dry eye is a disorder of the tear film due to tear deficiency or excessive evaporation, which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort. Daily topical administration of TRPM8 agonist may increase basal tear production in patients with mild to moderate dry eye disease. Also, it may provide symptom relief and improve patients quality of life related to ocular discomfort.
Ethics approval(s)	Institutional Review Board of Chonnam National University Hospital, 10/07/2014, IRB No. CNUH 2014-171
Health condition(s) or problem(s) studied	Dry eye
Intervention	Patients will be randomized to be treated with TRPM8 agonist (1-(Diisopropyl-phosphinoyl)-nonane) dissolved in distilled water (2 mg/mL) or vehicle (distilled water) topically delivered using the stick and topically applied in the margin of upper eyelid 4 times daily (every 6 hours) for 2 weeks.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	1-(Diisopropyl-phosphinoyl)-nonane
Primary outcome measure(s)	1. Basal tear secretion (baseline, 1 week, and 2 weeks follow-up) – assessed by Schirmer score 2. Symptom score assessed by three questionnaires at baseline, 1 week, and 2 weeks follow-up: 2.1. Visual analogue score (VAS) 2.2. Ocular surface disease index (OSDI) 2.3. Computer vision syndrome (CVS) related symptoms
Key secondary outcome measure(s)	1. Tear-film break up time (baseline, 1 week, and 2 weeks follow-up) - the time before the defect of fluorescein dye appeared in the stained tear film was measured and recorded (measured TBUT 3 times and averaged) 2. Keratoepitheliopathy score (baseline, 1 week, and 2 weeks follow-up) – after staining the cornea with fluorescein dye, the score was obtained by multiplying the stained area (0-3) by stained density (0-3) Area (0, no punctate staining; 1, area occupied less than 1/3 of the cornea; 2, area occupied 1/3 to 2/3 of the cornea; 3, area occupied greater than 2/3 of the cornea) Density (0, no punctate staining; 1, sparse density; 2, moderate density; 3, high density and the overlapped lesions)
Completion date	31/08/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	40
Key inclusion criteria	1. Dry eye symptoms for more than 3 months despite the use of artificial tears 2. Low tear film break-up time (TBUT) (≤ 7 seconds) 3. Low Schirmer score (≤ 10 mm/5 min) 4. Presence of corneal and conjunctival epithelial damage
Key exclusion criteria	1. History of any ocular disease other than DED 2. Meibomian gland dysfunction 3. Contact lens use 4. Ocular trauma or surgeries 5. Presence of an uncontrolled systemic disease that could affect ocular surface condition 6. Punctual plugs 7. Used any eye drops other than artificial tears 8. Used any systemic medication that can cause dry eye 9. Pregnant
Date of first enrolment	01/07/2015
Date of final enrolment	01/08/2015

Locations

Countries of recruitment

Korea, South

Study participating centre

Department of Ophthalmology

Chonnam National University Medical School and Hospital
KS0008
Korea, South

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	26/06/2017	23/01/2019	Yes	No
Results article	results	15/11/2018	23/01/2019	Yes	No

Editorial Notes

23/01/2019: Publication references added