Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Illinois at Chicago
Must be taking: Anti-diabetes
Must not be taking: Melatonin, Antidepressants, Antipsychotics, Sedatives
Disqualifiers: Stroke, Dementia, Cancer, others
No Placebo Group
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This study explores the use of melatonin in patients with diabetic retinopathy
Will I have to stop taking my current medications?
The trial requires that you stop using melatonin, antidepressants, antipsychotics, and sedatives or hypnotics. If you are taking any of these, you would need to stop before participating.
What data supports the effectiveness of the drug melatonin for diabetic retinopathy?
Research suggests that melatonin, a hormone known for its anti-inflammatory properties, can protect retinal cells and reduce inflammation in diabetic retinopathy, potentially making it a useful treatment for this condition.
12345Is melatonin safe for human use?
Melatonin, including its prolonged-release form (Circadin), has been shown to be well tolerated in humans, with mild side effects like nausea, dizziness, restlessness, and headache reported in a small number of cases. It has been used safely in various conditions, including sleep disorders and diabetes-related complications.
26789How does the drug melatonin differ from other treatments for diabetic retinopathy?
Melatonin is unique in treating diabetic retinopathy because it targets abnormal melatonin regulation linked to sleep and circadian rhythm issues, which are associated with the condition. Unlike other treatments, it may help by improving melatonin levels, potentially reducing oxidative stress and inflammation, and downregulating harmful proteins like VEGF, which are involved in the progression of diabetic retinopathy.
124510Eligibility Criteria
This trial is for people aged 40-65 with Type 2 diabetes and moderate diabetic retinopathy. Candidates must not have severe memory issues, major untreated diseases like cancer or heart failure, uncontrolled blood pressure or diabetes, recent severe hypoglycemia, certain eye conditions, or be using melatonin or specific psychiatric drugs.Inclusion Criteria
I have moderate or worse diabetic eye disease.
I have type 2 diabetes or my A1C level is 6.5% or higher.
I am between 40 and 65 years old.
Exclusion Criteria
I have had a stroke or a mini-stroke before.
You use illegal drugs.
I am currently taking melatonin.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive melatonin or placebo for 8 weeks to assess sleep and circadian regulation
8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests if melatonin can help patients with diabetic retinopathy. Participants will either receive melatonin or a placebo (a substance with no active drug). The goal is to see if there's any improvement in their condition compared to those who don't take the real medication.
2Treatment groups
Active Control
Group I: ControlActive Control1 Intervention
Placebo
Group II: MelatoninActive Control1 Intervention
Melatonin
Melatonin is already approved in European Union, European Union, United States for the following indications:
🇪🇺 Approved in European Union as Circadin for:
- Insomnia in adults aged 55 and over
- Sleep disorders in children with autism spectrum disorder
🇪🇺 Approved in European Union as Slenyto for:
- Insomnia in children and adolescents aged 2-18 with autism spectrum disorder
🇺🇸 Approved in United States as Melatonin for:
- Sleep disorders in children with autism spectrum disorder
- Insomnia in adults
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Illinois at ChicagoChicago, IL
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Who Is Running the Clinical Trial?
University of Illinois at ChicagoLead Sponsor
University of ChicagoCollaborator
References
Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus. [2020]To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients.
Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy. [2021]Recent evidence suggests that diabetic retinopathy (DR) is associated with abnormal melatonin regulation, possibly related to dysfunction of the melanopsin-expressing intrinsically photosensitive retinal ganglion cells. This study explored melatonin regulation in type 2 diabetes (T2D) patients with DR and its relation to sleep and circadian functioning.
Melatonin inhibits Müller cell activation and pro-inflammatory cytokine production via upregulating the MEG3/miR-204/Sirt1 axis in experimental diabetic retinopathy. [2021]Diabetic retinopathy (DR) is the most common ocular complication caused by diabetes mellitus and is the main cause of visual impairment in working-age people. Reactive gliosis and pro-inflammatory cytokine production by Müller cells contribute to the progression of DR. Melatonin is a strong anti-inflammatory hormone, mediating the cytoprotective effect of a variety of retinal cells against hyperglycemia. In this study, melatonin inhibited the gliosis activation and inflammatory cytokine production of Müller cells in both in vitro and in vivo models of DR. The melatonin membrane blocker, Luzindole, invalidated the melatonin-mediated protective effect on Müller cells. Furthermore, melatonin inhibited Müller cell activation and pro-inflammatory cytokine production by upregulating the long noncoding RNA maternally expressed gene 3/miR-204/sirtuin 1 axis. In conclusion, our study suggested that melatonin treatment could be a novel therapeutic strategy for DR.
Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes. [2022]Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = -2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = -0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = -0.013, 95% CI: -0.038, -0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.
Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy. [2021]The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.
Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. [2021]Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each,
Diabetes mellitus and melatonin: Where are we? [2022]Diabetes mellitus (DM) and diabetes-related complications are amongst the leading causes of mortality worldwide. The international diabetes federation (IDF) has estimated 592 million people to suffer from DM by 2035. Hence, finding a novel biomolecule that can effectively aid diabetes management is vital, as other existing drugs have numerous side effects. Melatonin, a pineal hormone having antioxidative and anti-inflammatory properties, has been implicated in circadian dysrhythmia-linked DM. Reduced levels of melatonin and a functional link between melatonin and insulin are implicated in the pathogenesis of type 2 diabetes (T2D). Additionally, genomic studies revealed that rare variants in melatonin receptor 1b (MTNR1B) are also associated with impaired glucose tolerance and increased risk of T2D. Moreover, exogenous melatonin treatment in cell lines, rodent models, and diabetic patients has shown a potent effect in alleviating diabetes and other related complications. This highlights the role of melatonin in glucose homeostasis. However, there are also contradictory reports on the effects of melatonin supplementation. Thus, it is essential to explore if melatonin can be taken from bench to bedside for diabetes management. This review summarizes the therapeutic potential of melatonin in various diabetic models and whether it can be considered a safe drug for managing diabetic complications and diabetic manifestations like oxidative stress, inflammation, ER stress, mitochondrial dysfunction, metabolic dysregulation, etc.
Optimization of light and melatonin to phase-shift human circadian rhythms. [2019]Both light and melatonin, appropriately timed, have been shown to phase-shift human circadian rhythms. In addition, both light and melatonin have acute physiological and behavioural effects. Depending on the dose, melatonin can reduce core body temperature and induce sleepiness. Conversely, light at night increases body temperature and enhances alertness and performance. The acute and phase-shifting effects of light and melatonin have justified their investigation and use in the treatment of circadian rhythm sleep disorders. Melatonin is the treatment of choice for blind people with non-24 h sleep/wake disorder. Current research is directed towards optimizing these therapies with respect to time of administration, dose and formulation of melatonin, intensity, duration and spectral composition of light. Our studies in totally blind people with non-24 h sleep/wake disorder have shown that, in addition to improving sleep, daily administration of melatonin can entrain their free-running circadian rhythms. The ability of melatonin to entrain free-running rhythms depends, in part, on the time of melatonin administration relative to the subject's circadian phase. Subjects who were entrained by melatonin began their treatment in the phase advance portion (CT 6-18) of the published melatonin phase-response curves (PRCs), whereas those who failed to entrain began their melatonin treatment in the delay portion of the PRC. Whether the effect of light on the human circadian axis can be optimized by altering its spectral composition has been investigated. Recently, it was demonstrated that light-induced melatonin suppression in humans is sensitive to short wavelength light (420-480 nm; lambda(max) approximately 460 nm), a response very different to the classical scotopic and photopic visual systems. Whether other nonvisual light responses (e.g. circadian phase resetting) show a similar spectral sensitivity is currently being studied.
Plasma melatonin levels in patients with diabetic retinopathy secondary to type 2 diabetes. [2021]Melatonin is reported to be related to diabetes mellitus (DM) risk; however, the effect of melatonin on diabetic retinopathy (DR) risk remains unclear.
Improved Melatonin Delivery by a Size-Controlled Polydopamine Nanoformulation Attenuates Preclinical Diabetic Retinopathy. [2023]Oxidative stress, reactive oxygen species generation, and overexpression of VEGF are signatory events in diabetic retinopathy. The downregulation of VEGF and anti-inflammatory action pave the way for diabetic retinopathy (DR) therapy. In that, lower absorption kinetics of melatonin limits its immense therapeutic potential. Hence, we have demonstrated a reverse microemulsion method to synthesize melatonin-loaded polydopamine nanoparticles to replenish both at a single platform with an improved melatonin delivery profile. The study has evaluated in vitro and in vivo protection efficiency of biocompatible melatonin-loaded polydopamine nanoparticles (MPDANPs). The protection mechanism was explained by downregulation of VEGF, CASPASE3, and PKCδ against high-glucose/streptozotocin (STZ)-induced insults, in vitro and in vivo. The anti-inflammatory and antiangiogenic effect and potential of MPDANPs to enhance melatonin in vivo stability with prolonged circulation time have proved MPDANPs as a potential therapeutic candidate in DR management. The DR therapeutic potential of MPDANPs has been arbitrated by improving the bioavailability of melatonin and inhibition of VEGF-PKCδ crosstalk in vivo.