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CompletedNCT06520007Updated Jul 25, 2024

Comparison Between Continuous and Pulsed Oral Doxycycline Treatment Protocols for Refractory Meibomian Gland Dysfunction

An observational study in Meibomian Gland Dysfunction, Blepharitis and Doxycycline Adverse Reaction, sponsored by University of Milan. Completed at 1 site in Italy. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2024-07-25.

Sponsored by University of Milan · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
65
Ages
18 Years to 100 Years
Sex
All
01

Study summary

The goal of this observational study (spontaneous, non-randomised, prospective cohort, phase IV) is to compare the efficacy and safety of two different oral doxycycline treatment protocols (LCP - Low dose continuous protocol \& FPP - Full dose pulsed protocol) for meibomian gland dysfunction (MGD) in patients with refractory MGD (OSDI > 13 after at least 2 months treatment with warm compresses and lacrimal substitutes - first-line therapy). Systemic doxycycline doesn't have a standardized treatment protocol and this is why those patients are treated as in normal clinical practice. The main questions it aims to answer are:

Which treatment protocol has a greater impact on patient symptoms during the follow-up (OSDI score reduction)? Which treatment protocol has a greater impact on patient signs during the follow-up (TBUT and corneal staining variations)? Which treatment protocol is safer (in terms of adverse events rate)?

Participants will be visited every 3 months (V0-V1-V2-V3) with signs and symptoms assessment (TBUT, corneal staining, OSDI score) after being treated for 3 months with the assigned doxycycline treatment protocol (LCP or FPP).

Read the detailed description

This spontaneous, prospective, non-randomized, parallel-group, phase IV study was conducted in compliance with the tenets of the Declaration of Helsinki.

All study participants were fully consented, and written informed consent was obtained.

This study included patients with refractory MGD. Refractory MGD is defined as symptomatic MGC (OSDI > 13 points) despite 2 months of first-line treatment with lacrimal substitutes 3 times per day and meibomian gland expression with warm compresses twice per day.

The study will consist of 3 visits: Baseline (day 0), Visit 2 (day 90 ± 5 - 3rd month), Visit 3 (day 180 ± 5 - 6 month). At each visit, patients will receive an OSDI questionnaire, NIBUT, type I Schirmer test and AS assessment, including TBUT, corneal staining (Oxford scale) At baseline, eligible patients will be enrolled and treated with the assigned protocol. The investigators will assign the protocol (non-randomized) in a 1:1 ratio.

At Visit 2, NIBUT, TBUT, Oxford scale and OSDI improvement will be evaluated compared with Visit 1. Patients will be carefully asked about their compliance with the treatment. Patients who interrupted the treatment for adverse events or low compliance (\<75% of the protocol adherence) will exit the study and be excluded from the analysis.

At Visit 3, the study population will be evaluated as done in Visit 2

The protocols in the study are the following:

LCD (low-dose continuous protocol) - 50 mg of doxycycline for three months FPP ( Full-dose pulsed protocol) - 100 mg of doxycycline for the first 15 days of the month for three months.

The enrollment period will last about 6 months. Therefore, the study will end about 6 months after the last patient enrols.

02

Conditions studied

  • Meibomian Gland Dysfunction
  • Blepharitis
  • Doxycycline Adverse Reaction

Keywords

  • Meibomian gland dysfunction
  • Ocular surface disease
  • Doxycycline
  • Blepharitis
03

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients with refractory meibomian gland dysfunction (MGD). Refractory MGD is defined as symptomatic MGD (OSDI > 13 points) despite 2 months of first-line treatment with lacrimal substitutes 3 times per day and meibomian gland expression with warm compresses twice per day.

Inclusion criteria

  • 18 years or older
  • Provided written informed consent
  • OSDI score of 13 or more at the baseline visit after at least two months of first-line therapy (artificial tears and warm compresses)
  • Clinical diagnosis of MGD
  • Type 1 Schirmer test > 10 mm
  • No previous history of allergy or sensitivity to doxycycline,
  • No use of additional topical or systemic antibiotics for the prior 2 months
  • No use of topical anti-inflammatory agents (ex: corticosteroids or cyclosporine) for the prior 3 months.

Exclusion criteria

Exclusion criteria

  • Active ocular inflammation in either eye,
  • Demodex blepharitis,
  • Ocular surgery within the past 3 months of baseline examination,
  • Structural ocular surface and eyelid abnormalities.
  • Sjögren's syndrome
  • Rheumatoid arthritis
  • Other systemic diseases resulting in dry eye
  • Known autoimmune disease
  • Doxycycline allergy or sensitivity
  • History of antibiotic therapy at any time within 2 months of the commencement of study
  • Use of significant calcium supplementation or other medications that could interfere with doxycycline absorption (es: Iron supplementation)
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
65 participants (actual)
Patient registry
No

Groups and cohorts

  • LCP - Low dose continuous protocol

    Assumption of 50 mg of oral doxycycline per day for 3 months

    Drug: Doxycyclin

  • FPP - Full dose pulsed protocol

    Assumption of 100 mg of oral doxycycline per day for 15 days per month (with a subsequent 15 days of washout) for 3 months

    Drug: Doxycyclin

Interventions

  • DrugDoxycyclin

    The drug has been prescribed, as in normal clinical practice, with the National Healthcare System. Patients have been fully informed about interactions, toxicity and posology schedule.

05

What researchers measure

Primary outcomes

  1. OSDI score

    Ocular Surface Disease Index

    Time frame: Baseline - 3 months (90 days ± 5 days) - 6 months (180 days ± 5 days)

Secondary outcomes

  1. TBUT

    Tear break-up time

    Time frame: Baseline - 3 months (90 days ± 5 days) - 6 months (180 days ± 5 days)

  2. Corneal staining

    Oxford scale has been use to assess corneal staining

    Time frame: Baseline - 3 months (90 days ± 5 days) - 6 months (180 days ± 5 days)

  3. Adverse events

    Number of dropouts due to drug toxicity

    Time frame: From baseline up to the 3rd month

06

Study locations

1 site
  • ASST Santi Paolo e Carlo - Ospedale San Paolo
    Milano, MI 20142, Italy
07

References and documents

Study documents

  • Study protocol · Mar 10, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06520007
Lead sponsor
University of Milan
Responsible party
Paolo Fogagnolo (Associate professor, University of Milan) — Principal investigator
First posted
Jul 25, 2024
Start date
Mar 1, 2023
Primary completion
May 1, 2024
Completion
May 1, 2024
Last update
Jul 25, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.

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