Trial Outcomes & Findings for Effects of Carboxymethylcellulose Artificial Tears on the Eye Microbiome (NCT NCT05292755)

NCT ID: NCT05292755

Last Updated: 2023-04-20

Results Overview

Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Faith's phylogenetic diversity was used as a measure of species richness, calculated as the sum of all phylogenetic tree branch lengths using the QIIME2 faith\_pd plugin. The units for this measure are the number of nucleotide substitutions (phylogenetic distance, i.e. length) per branch, which is a scale measure from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species richness.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

80 participants

Primary outcome timeframe

Assessed at day 1 and day 7, day 7 reported.

Results posted on

2023-04-20

Participant Flow

Participant milestones

Participant milestones
Measure
Carboxymethylcellulose (CMC) Artificial Tears
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Overall Study
STARTED
40
40
Overall Study
COMPLETED
35
31
Overall Study
NOT COMPLETED
5
9

Reasons for withdrawal

Reasons for withdrawal
Measure
Carboxymethylcellulose (CMC) Artificial Tears
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Overall Study
Lost to Follow-up
5
9

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=40 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=40 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Total
n=80 Participants
Total of all reporting groups
Age, Continuous
41.1 years
STANDARD_DEVIATION 17.4 • n=40 Participants
40.2 years
STANDARD_DEVIATION 13.8 • n=40 Participants
40.6 years
STANDARD_DEVIATION 15.6 • n=80 Participants
Sex: Female, Male
Female
27 Participants
n=40 Participants
28 Participants
n=40 Participants
55 Participants
n=80 Participants
Sex: Female, Male
Male
13 Participants
n=40 Participants
12 Participants
n=40 Participants
25 Participants
n=80 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.
Region of Enrollment
United States
40 Participants
n=40 Participants
40 Participants
n=40 Participants
80 Participants
n=80 Participants
Contact lens use
9 Participants
n=40 Participants
10 Participants
n=40 Participants
19 Participants
n=80 Participants
Ocular surgery history
7 Participants
n=40 Participants
10 Participants
n=40 Participants
17 Participants
n=80 Participants

PRIMARY outcome

Timeframe: Assessed at day 1 and day 7, day 7 reported.

Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Faith's phylogenetic diversity was used as a measure of species richness, calculated as the sum of all phylogenetic tree branch lengths using the QIIME2 faith\_pd plugin. The units for this measure are the number of nucleotide substitutions (phylogenetic distance, i.e. length) per branch, which is a scale measure from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species richness.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Species Richness
11.0 units on a scale
Standard Deviation 2.1
11.1 units on a scale
Standard Deviation 3.3

PRIMARY outcome

Timeframe: Assessed at day 1 and day 7, day 7 reported.

Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold. Shannon's diversity index was used as a measure of species diversity, calculated as the sum of -p/ln(p), where p is the proportion of the sample made up of each OTU using the QIIME2 shannon\_pd plugin. This measure is a unitless scale proportion ranging from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species diversity.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Species Diversity
3.9 score on a scale
Standard Deviation 1.1
4.1 score on a scale
Standard Deviation 1.1

PRIMARY outcome

Timeframe: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.

Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Unweighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin. The unweighted UniFrac is a unitless scale proportion ranging from zero to one. Greater UniFrac distances indicate greater beta diversity.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Beta Diversity (Unweighted UniFrac)
0.482 score on a scale
Interval 0.388 to 0.574
0.529 score on a scale
Interval 0.417 to 0.618

PRIMARY outcome

Timeframe: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.

Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Weighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin, with samples weighted by abundance of species. The weighted UniFrac (weighted by number of duplicate OTUs) is a unitless scale proportion ranging from zero to infinity. Greater UniFrac distances indicate greater beta diversity.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Beta Diversity (Weighted UniFrac)
0.584 score on a scale
Interval 0.416 to 0.839
0.593 score on a scale
Interval 0.468 to 0.797

SECONDARY outcome

Timeframe: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.

The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Participants conducted a survey before and after intervention, and the difference will be used as the outcome measure. The OSDI ranges from 0 to 48, and a higher score indicates greater ocular surface dryness. If reporting the difference, a more negative change in OSDI indicates greater improvement in dry eye symptoms. Pairwise Wilcoxon signed rank tests were used to compare changes in OSDI between intervention groups at a two-tailed 95% confidence interval.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Ocular Surface Disease Index Score
-1 score on a scale
Interval -5.5 to 0.0
-2 score on a scale
Interval -4.0 to 0.0

SECONDARY outcome

Timeframe: Assessed at day 7

Patients will be asked 1 week after intervention how many times they administered eye drops each day. This measures compliance with intervention, ranging from zero drops per day to infinite drops per day. If a patient is perfectly compliant, the number of drops should be 3. Mann-U-Whitney tests were used to compare compliance between intervention groups at a two-tailed 95% confidence interval.

Outcome measures

Outcome measures
Measure
Carboxymethylcellulose (CMC) Artificial Tears
n=35 Participants
Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
Preservative-free, CMC-free Artificial Tears
n=31 Participants
Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Artificial Tear Use
2.86 eyedrops per day
Standard Deviation 0.81
2.16 eyedrops per day
Standard Deviation 0.82

Adverse Events

Carboxymethylcellulose (CMC) Artificial Tears

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Preservative-free, CMC-free Artificial Tears

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Yujia Zhou

University of Florida

Phone: 3053429166

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place