Effects of Melatonin Supplementation on Sleep Quality in Patients with Advanced Glaucoma

Not Applicable

Completed

• Conditions: Glaucoma; Sleep Disturbance; Circadian Rhythm; Melatonin; Actigraphy

• Registration Number: NCT06868745
• Lead Sponsor: University of Sao Paulo

Brief Summary

A prospective, randomized, parallel, crossover, double-blind therapeutic clinical trial was conducted in accordance with the principles of the Resolution nº 466/12 of the National Health Council and was approved by the Ethics and Research Committee of the Federal University of São Paulo, project CEP/UNIFESP n:1023/2020, CAAE: 36946620.9.0000.5505. Written informed consent was obtained from all participants. The study was conducted at the Glaucoma Division and the Department of Psychobiology at the Federal University of São Paulo - UNIFESP/EPM and at the Laser Vision Eye Hospital - Santos/SP between May/2022 and July/2023.

Detailed Description

The study included 64 patients with a diagnosis of advanced primary open-angle glaucoma in both eyes.

Patients were classified as glaucoma cases if they had at least 3 repeatable, consecutive, abnormal visual field test results, defined as a pattern standard deviation (PSD) outside the 95% normal confidence limits or a Glaucoma Hemifield Test (GHT) result outside normal limits matching the appearance of the optic disc, presenting a Mean deviation of \<-12.00 dB in the better eye(7,14,17), according to the Hoddap-Parish-Anderson classification for glaucoma severity, using the SITA-Standard strategy, with no involvement of the fixation region (absence of statistically significant points in the central 5º for both total and pattern deviation).

Patients were considered as glaucomatous if they had signs of glaucomatous optic neuropathy based on optic disc stereophotographs. Evidence of glaucomatous damage to the optic disc nerve was considered if they had RNFL defects or localized or diffuse neuroretinal rim loss. There were 32 participants in the melatonin group and 32 in the placebo group. The age range of the volunteers was over 40 years and under 80 years.

Subjects were excluded if they were younger than 40 or older than 80 years; best-corrected visual acuity of less than 0.4 logMAR; Patients who work at night or recently traveled across time zones, use topical or systemic medications that could disrupt circadian rhythms, for example Benzodiazepines, Non-benzodiazepines (hypnotics), Sedative antidepressants, Melatonin and melatonin agonists, patients with previously defined obstructive sleep apnea or other disorders such as depression and insomnia were excluded. Only patients with an open angle on gonioscopy were included in our study.

Each participant received melatonin 5 mg and placebo for a period of 30 days at different time points. The packages were identical, each labeled with the letters F and I. Only the supervisor Dr. Augusto Paranhos Junior, had knowledge of which package contained the original drug. Additionally, the pills within the packages were identical and supplied by the same researcher, who was not informed about the significance of the letters on the packaging.

On day 0 (D0 - before starting the medication), subjects completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) to assess subjective sleep quality and daytime sleepiness, respectively. At D0, they also completed the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The 24-hour daily profile of sleep parameters was assessed on a single night by actigraphy.

Questionnaires and actigraphy assessments were carried out, 30 days after each medication and in the wash out interval 7 days discontinuing the use of the medication.

Study Timeline

• Study Start: 2022-05-04
• Primary Completion: 2023-07-20
• Study Completion: 2024-06-26
• Study First Submitted: 2025-01-25
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-05
• Last Update Submitted: 2025-03-05
• Study First Posted: 2025-03-11
• Last Update Posted: 2025-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• Diagnosis of Primary Open-Angle Glaucoma: Must have a confirmed diagnosis of primary open-angle glaucoma.
• Cup-to-Disc Ratio > 0.6: The ratio of cup to disc on optic disc imaging must be greater than 0.6.
• Visual Acuity ≥ 0.4 logMAR: Participants must have a visual acuity of 0.4 logMAR or better in the better eye.
• Age: Participants must be aged 40 to 80 years, inclusive.

Exclusion Criteria

• Pregnancy: Female participants who are pregnant or planning to become pregnant during the study period.
• Current or Past Diagnosis of Depression: Participants with a current or past history of depression.
• Corneal or Retinal Diseases: History or active disease of the cornea or retina (e.g., diabetic retinopathy, macular degeneration).
• Shift Work: Participants who work night shifts or irregular hours.
• Travel Across Time Zones: Participants who have traveled across time zones in the last 30 days prior to enrollment.
• Diagnosed Obstructive Sleep Apnea: History of obstructive sleep apnea or a current diagnosis of the condition.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma	From enrollment to the end of treatment in 2 months	To compare the quality of sleep in patients with advanced glaucoma after 30 days of melatonin 5 mg and 30 days of placebo. The comparison of efficacy between groups will be assessed based on the improvement in sleep quality between medications.

Secondary Outcome Measures

Name	Time	Method
Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma	From registration to the end of treatment in 2 months	To compare the effects on sleep quality after using melatonin 5 mg and placebo. The effects on sleep quality will be measured by the following assessments: questionnaire, 25-Item National Eye Institute Visual Function Questionnaire, quality of life is measured on 25 levels, with the last level being the best rating.

Trial Locations

Locations (1)

Casa; 🇧🇷 Santos, Sao Paulo, Brazil