Clinical trial NCT06868745: Effects of Melatonin Supplementation on Sleep Quality in Patients With Advanced Glaucoma
Official title: Randomized Clinical Trial: Effects of Melatonin Supplementation on Sleep Quality in Patients With Advanced Glaucoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glaucoma
Sleep Disturbance
Circadian Rhythm
Melatonin
Actigraphy
Keywords: glaucoma
sleep disturbance
circadian rhythm
melatonin
actigraph
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 64
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective, randomized, parallel, cross-over, and double-blind therapeutic-type clinical study was conducted at the Glaucoma Division and the Department of Psychobiology at the Federal University of São Paulo - UNIFESP/EPM and the Eye Hospital Visao Laser in Santos/SP. The study involved 64 patients, with an age range of over 40 and under 80 years old. All participants underwent a complete ophthalmological evaluation and completed questionnaires on sleep quality (PSQI-BR), the Epworth Sleepiness Scale, and the Vision Function Questionnaire (NEI VFQ-25). Each participant received either 5mg of melatonin or a placebo for 30 days at different times. During this period, they were assessed using actigraphy, questionnaires, and examinations on day 0 (before starting the medication) and on day 30. Afterward, the use of the medication was discontinued.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma
timeFrame: From enrollment to the end of treatment in 2 months
Secondary outcomes:
measure: Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma
timeFrame: From registration to the end of treatment in 2 months
measure: Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma
timeFrame: From registration to the end of treatment in 2 months
measure: Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma
timeFrame: From registration to the end of treatment in 2 months
measure: Effects of Melatonin Replacement on Sleep Quality of Patients with Advanced Glaucoma
timeFrame: From registration to the end of treatment in 2 months
Other outcomes:
Locations:
city: Santos
country: Brazil
facility: Casa
state: Sao Paulo
Study officials:
References: