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

Trial Summary

What is the purpose of this trial?

Caffeine is the most widely consumed drinking nutrient in the world. Caffeine effects various organs and the vascular system. It decreases ocular blood flow due to vasoconstriction.

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 caffeine safe for human consumption?

Research shows that caffeine, when combined with other medications like paracetamol or ibuprofen, is generally safe for treating tension-type headaches, with no significant difference in safety compared to other treatments like naproxen or placebo. ^{1 2 3 4 5}

How does caffeine consumption differ from other treatments for glaucoma?

Caffeine is unique in its potential use for glaucoma as it is not a standard treatment for this condition. Unlike typical glaucoma medications that reduce eye pressure, caffeine's role as an adjuvant (helper) in pain relief is due to its action on adenosine receptors, which is different from the mechanisms of traditional glaucoma drugs. ^{5 6 7 8 9}

Research Team

M. Reza Razeghinejad, MD

Principal Investigator

Wills Eye Hospital

Eligibility Criteria

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 am between 18 and 90 years old.

I have been diagnosed with primary open angle glaucoma.

I have healthy eyes with no eye diseases.

Exclusion Criteria

I cannot focus my eyes on a specific point.

Mental illness or alcohol addiction

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Pharmacovigilance update]. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

The use of ibuprofen plus caffeine to treat tension-type headache. [2019]

4. Ireland pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. [2023]

5. England 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. [2018]

6. India 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. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of combined dipyrone, isometheptene and caffeine in the treatment of mild-to-moderate primary headache episodes. [2015]

9. England 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. [2015]