Caffeine Consumption for Glaucoma

Overseen By Jeanne Molineaux, COA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wills Eye

Disqualifiers: Diabetic retinopathy, Cardiac disease, Mental illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how caffeine affects blood flow in the eyes, particularly for individuals with glaucoma, a condition that can damage the optic nerve. Participants will take a caffeine tablet, and researchers will observe the eye's response over a few hours. The trial includes individuals with primary open-angle or angle-closure glaucoma and healthy individuals without eye diseases. It suits those who consume less than one cup of coffee per day and have been diagnosed with glaucoma or have healthy eyes. As an unphased trial, it offers participants the chance to contribute to understanding caffeine's effects on eye health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research shows that caffeine is generally safe for people, including those with glaucoma. Studies have found that pure caffeine doesn't significantly affect intraocular pressure in individuals with glaucoma, meaning it doesn't worsen the condition. However, consuming large amounts of caffeine daily might increase the risk of glaucoma in those genetically predisposed to higher eye pressure.

Most people tolerate caffeine well, though side effects like jitteriness or sleep disturbances can occur, especially with large doses. In this study, participants will take one 200 mg caffeine tablet, equivalent to about two cups of coffee. This is considered a moderate amount and is usually safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for glaucoma, which often involve medications like prostaglandin analogs or beta-blockers to reduce eye pressure, this approach uses caffeine. Researchers are excited about caffeine because it is a common, well-tolerated substance that could offer a new mechanism of action. While traditional treatments focus on lowering intraocular pressure, caffeine might help improve blood flow to the optic nerve. This could provide an additional layer of protection for the eyes, possibly slowing the progression of glaucoma in a novel way.

What evidence suggests that caffeine might be an effective treatment for glaucoma?

This trial will compare the effects of caffeine consumption on glaucoma patients and healthy controls. Research has shown that drinking caffeine typically does not increase the risk of developing primary open-angle glaucoma (POAG). However, some studies suggest that individuals with a genetic tendency for higher eye pressure might face an increased risk of glaucoma with high caffeine consumption. One study found that applying caffeine directly to the eye did not alter eye pressure in people with glaucoma. Overall, the results are mixed, but high caffeine intake could be risky for certain individuals. ^{2 4 5 6 7}

Who Is on the Research Team?

M. Reza Razeghinejad, MD

Principal Investigator

Wills Eye Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 with primary open-angle glaucoma, as well as healthy individuals without eye diseases. It's not suitable for those with conditions affecting eye test results, severe cataracts, nystagmus, macular degeneration (except mild), diabetic retinopathy, certain optic neuropathies or corneal issues, rheumatologic diseases like Raynaud's phenomenon, pregnant or breastfeeding women, mental illness or alcohol addiction.

Inclusion Criteria

I have been diagnosed with primary open angle glaucoma.

I have healthy eyes with no eye diseases.

Exclusion Criteria

Mental illness or alcohol addiction

Possible tolerance to caffeine (drinking more than 1 cup coffee per day)

I cannot focus my eyes on a specific point.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants complete baseline study tasks before caffeine ingestion

1 day

1 visit (in-person)

Caffeine Ingestion and Monitoring

Participants ingest a 200 mg caffeine tablet and undergo OCTA scans 1 and 2 hours post-ingestion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any delayed effects of caffeine on ocular blood flow

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine

Trial Overview The study is looking at the effects of a caffeine tablet on people with glaucoma compared to healthy subjects. The focus is on how caffeine influences ocular blood flow and potentially affects the vascular system within the eyes.

How Is the Trial Designed?

Group I: Glaucoma Patients Active Control 1 Intervention

Eligible participants include patients with mild, moderate or advanced primary open angle glaucoma (POAG) or primary angle closure glaucoma (PACG). Each participant will complete baseline study tasks. Each participant will then receive one 200 mg caffeine tablet to ingest. Study tasks will be performed 1 hour and 2 hours after caffeine ingestion.

Group II: Healthy controls Active Control 1 Intervention

Eligible participants include healthy subjects with no eye diseases. Each participant will complete baseline study tasks. Each participant will then receive one 200 mg caffeine tablet to ingest. Study tasks will be performed 1 hour and 2 hours after caffeine ingestion.

Who Is Running the Clinical Trial?

Wills Eye

Lead Sponsor

Trials

81

Recruited

15,400+

Published Research Related to This Trial

The combination of paracetamol (1,000 mg) and caffeine (130 mg) (PCF) was found to be well-tolerated and effective for treating tension-type headache (TTH) in an Italian population, based on a multicenter, randomized, double-blind, placebo-controlled trial.

Both PCF and naproxen sodium (550 mg) showed significant efficacy compared to placebo, but there was no significant difference in effectiveness between PCF and naproxen, indicating that PCF is a viable alternative for acute TTH treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. Pini, LA., Del Bene, E., Zanchin, G., et al.[2018]

The 22nd French pharmacovigilance meeting revealed 315 notifications of severe adverse effects linked to non-specific 'immunostimulants', with 68% of cases considered likely attributable to the drugs, including three fatalities.

The meeting highlighted that many adverse effects, both known and rare, continue to occur with various medications, emphasizing the need for better documentation and monitoring of drug safety, as well as the potential for immediate market withdrawal of drugs with poor risk-benefit ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highlights of the 22nd French pharmacovigilance meeting. [2007]

In a study of 297 patients, the initial effectiveness of Indoprocaf and sumatriptan for treating migraines was similar, with both achieving over 30% pain-free rates.

However, Indoprocaf showed significantly better results for re-dosing as a rescue medication, with 47% of patients pain-free compared to 27% for sumatriptan, indicating its potential advantage in managing recurring migraine attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study. Sandrini, G., Cerbo, R., Del Bene, E., et al.[2018]

In a study of 84 adult patients with mild-to-moderate primary headaches, the combination of dipyrone, isometheptene, and caffeine showed a higher rate of pain improvement compared to paracetamol and placebo, with 72.5% of patients experiencing pain relief after 120 minutes.

Although the combination therapy did not achieve a statistically significant sustained pain-free rate compared to paracetamol and placebo, it resulted in fewer patients needing rescue medication, indicating its potential effectiveness and excellent tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of combined dipyrone, isometheptene and caffeine in the treatment of mild-to-moderate primary headache episodes. de Souza Carvalho, D., Barea, LM., Kowacs, PA., et al.[2015]

Sofosbuvir has a significant interaction with amiodarone, leading to a risk of severe bradycardia, highlighting the need for caution when these drugs are used together.

SGLT2 inhibitors are associated with risks of diabetic ketoacidosis and bone fractures, indicating important safety considerations for patients using these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacovigilance update]. Dao, K., Chtioui, H., Rothuizen, LE., et al.[2016]

A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness and safety of combining ibuprofen with caffeine for treating tension-type headaches, building on previous evidence of caffeine's analgesic properties.

The study aims to confirm the pain-relieving effects of caffeine and explore how tension-type headaches can serve as a useful model for pain research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ibuprofen plus caffeine to treat tension-type headache. Diamond, S., Freitag, FG.[2019]

In a study of 57 malaria patients, the combination of Artemisinin-Based Combination Therapies (ACTs) with paracetamol significantly altered 24 out of 37 evaluated toxicity markers, indicating potential safety concerns with this treatment regimen.

The findings suggest that careful selection of ACTs plus paracetamol is crucial, especially for patients with existing health conditions, due to the observed changes in various biochemical and haematological indices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. Aghahowa, SE., Ozolua, RI., Bafor, EE., et al.[2023]

A Cochrane review of 19 studies involving 7238 patients found that caffeine significantly enhances the effectiveness of common pain relievers like paracetamol, ibuprofen, or aspirin, with a number needed to treat (NNT) of about 16, which is similar to the effect of doubling the dose of these medications.

Caffeine is generally well-tolerated in normal amounts (around 300 mg per day) and has a favorable risk-benefit profile, making it a useful adjunct in pain management while also offering potential benefits for conditions like Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Caffeine in analgesics--myth or medicine?]. Petersen, KU.[2019]

In a study of 54 patients with tension-type headaches, the combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) was found to be more effective than nimesulide, with 45% of patients pain-free at 2 hours compared to only 10% for nimesulide.

IndoProCaf also led to a greater percentage of patients achieving at least a 50% pain reduction at both 2 and 4 hours post-dose, indicating its potential for faster relief, while both treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension-type headache: a double-blind, randomized, nimesulide-controlled, parallel group, multicentre trial. Cerbo, R., Centonze, V., Grazioli, I., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3100584/

Caffeine Consumption and the Risk of Primary Open In this large, prospective study, overall caffeine consumption was not associated with risk of developing primary open-angle glaucoma (POAG). In one secondary ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18263806/

Caffeine consumption and the risk of primary open-angle ... Conclusions: Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high- ...

3. mountsinai.org mountsinai.org/about/newsroom/2021/high-caffeine-consumption-may-be-associated-with-increased-risk-of-blinding-eye-disease

High Caffeine Consumption may be Associated with ... Consuming large amounts of daily caffeine may increase the risk of glaucoma more than three-fold for those with a genetic predisposition to higher eye pressure.

4. oftalmoloji.org oftalmoloji.org/articles/caffeine-and-vision-effects-on-the-eye/tjo.galenos.2024.43895

Caffeine and Vision: Effects on the Eye Notably, topical 1% caffeine eye drops did not appear to change intraocular pressure in patients with primary open-angle glaucoma after 1 week ...

5. researchgate.net researchgate.net/publication/360505891_Habitual_coffee_consumption_increases_risk_of_primary_open-angle_glaucoma_A_Mendelian_randomization_study

Habitual Coffee Consumption Increases Risk of Primary ... A recent MR study on caffeine consumption and glaucoma suggest that higher coffee consumption is associated with a higher risk of open-angle ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3225459/

Effect of caffeine on the intraocular pressure in patients with ... Studies with pure caffeine convincingly demonstrate that caffeine does not have any significant effect on IOP in patients with glaucoma/ocular hypertension.

7. ucl.ac.uk ucl.ac.uk/news/2021/jun/high-caffeine-consumption-may-be-linked-increased-glaucoma-risk

High caffeine consumption may be linked to increased ... Consuming large amounts of daily caffeine may increase glaucoma risk for those with a genetic predisposition to higher eye pressure, finds a new study.