Clarithromycin for Excessive Daytime Sleepiness

Overseen By Tyler Blake

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Sleep apnea, Limb movement disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

83 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called clarithromycin to determine if it can reduce excessive daytime sleepiness in individuals with narcolepsy or idiopathic hypersomnia, a condition causing severe sleepiness. Researchers aim to understand clarithromycin's effects on sleepiness by examining its impact on brain activity, inflammation, gut bacteria, and spinal fluid. Participants will be randomly assigned to take either clarithromycin or a placebo for 14 days. This trial may suit those diagnosed with narcolepsy or idiopathic hypersomnia who remain sleepy despite current medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

Yes, if you are taking wake-promoting medications, you must be willing to stop them for at least 5 half-lives before the trial starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that clarithromycin is usually well-tolerated. In one study involving 3,437 participants, 20% experienced mild side effects, mostly digestive issues like upset stomachs. Only 1% of these side effects were serious, with no major problems affecting blood, liver, or other vital organs. Another study found no serious side effects, and participants felt less sleepy without any impact on reaction times. These findings suggest that clarithromycin is quite safe for short-term use to alleviate sleepiness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleepiness?

Clarithromycin is unique because it's being explored for excessive daytime sleepiness, a condition usually managed with stimulants like modafinil or armodafinil. Unlike these standard treatments, which mainly boost brain activity, clarithromycin is an antibiotic that might offer a novel mechanism by influencing sleep regulation pathways. Researchers are excited about its potential to provide a different therapeutic option, especially for those who may not respond well to current stimulant medications or who experience unwanted side effects. Plus, clarithromycin's well-known safety profile could make it a promising alternative for managing sleepiness.

What evidence suggests that clarithromycin might be an effective treatment for sleepiness in narcolepsy and idiopathic hypersomnia?

Research has shown that clarithromycin, which participants in this trial may receive, can help reduce sleepiness in individuals with conditions like narcolepsy and idiopathic hypersomnia. In one study, 64% of participants reported feeling less sleepy during the day after taking clarithromycin. Another study found that clarithromycin significantly improved sleepiness and related daily challenges. Although some people experienced side effects, many tolerated the treatment well. Overall, these findings suggest clarithromycin could help manage excessive daytime sleepiness by increasing alertness. ^{1 2 4 6 7}

Who Is on the Research Team?

Lynn Marie Trotti, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with narcolepsy or idiopathic hypersomnia who are either not taking wake-promoting meds, can stop them safely before the study, or still feel sleepy on these meds. They shouldn't have taken pre/probiotic supplements for six months and must not have other sleep disorders or conditions that could explain their sleepiness.

Inclusion Criteria

I don't take wake-promoting meds, or I'm willing to stop them before the study starts.

I have been diagnosed with idiopathic hypersomnia or narcolepsy.

You have not taken pre- or probiotic supplements for at least six months before the study starts.

Exclusion Criteria

Contraindication to any of the study procedures

I cannot take clarithromycin due to health reasons.

I do not have untreated sleep apnea, severe limb movement disorder, or uncontrolled metabolic disorders causing excessive sleepiness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive clarithromycin or placebo for 14 days to evaluate its effects on sleepiness in hypersomnia syndromes

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Clarithromycin
• Placebo

Trial Overview Researchers are testing clarithromycin against a placebo to see if it reduces sleepiness in those with narcolepsy and idiopathic hypersomnia. The study will also explore how this drug affects brain activity, inflammation, gut bacteria, and cerebrospinal fluid by using MRI scans among other methods.

How Is the Trial Designed?

Group I: Clarithromycin Experimental Treatment 1 Intervention

Participants in this study arm will receive clarithromycin for 14 days.

Group II: Placebo Placebo Group 1 Intervention

Participants in this study arm will receive a placebo to match clarithromycin for 14 days.

Clarithromycin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in European Union as Klaricid for:

• Acute bacterial exacerbation of chronic bronchitis
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in Canada as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a 5-week study involving 20 patients with hypersomnolence syndromes, clarithromycin significantly improved subjective measures of sleepiness compared to placebo, although it did not affect objective reaction times on a vigilance task.

The only notable side effect associated with clarithromycin was altered taste perception, with no serious adverse events reported, suggesting it may be a safe treatment option for patients with treatment-refractory hypersomnolence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial. Trotti, LM., Saini, P., Bliwise, DL., et al.[2018]

In a study of 507 Australian workers, 10.9% reported excessive daytime sleepiness, as indicated by Epworth Sleepiness Scale (ESS) scores greater than 10, which is a significant finding in the context of workplace health.

Excessive daytime sleepiness was weakly associated with sleep-disordered breathing and insomnia, but not significantly related to factors like age, sex, obesity, or the use of sleep medications, highlighting the need for further investigation into its causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daytime sleepiness and sleep habits of Australian workers. Johns, M., Hocking, B.[2022]

In a study involving 88 patients with essential hypertension, both trandolapril (2 mg) and enalapril (20 mg) significantly reduced 24-hour ambulatory blood pressure, demonstrating their efficacy in managing hypertension.

The reductions in mean systolic and diastolic blood pressure were comparable for both medications, indicating that they are similarly effective in lowering blood pressure over a 24-hour period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of a missed dose of trandolapril and enalapril on blood pressure control in hypertensive patients. Vaur, L., Dutrey-Dupagne, C., Boussac, J., et al.[2019]

In a study of 31 men with mild hypertension over 18 weeks, enalapril effectively lowered diastolic blood pressure in a dose-dependent manner, showing greater efficacy in white patients compared to black patients.

Enalapril was well tolerated by all participants, with no significant clinical or metabolic complications reported, confirming its safety as an antihypertensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril. Chrysant, SG., Brown, RD., Kem, DC., et al.[2019]

In a phase III study involving 250 adult patients with acute exacerbation of chronic bronchitis, clarithromycin modified release (MR) was found to be as effective as amoxicillin/clavulanic acid in treating the condition, with both treatments showing equivalent clinical and bacteriologic outcomes.

Clarithromycin MR had a better safety profile, resulting in fewer digestive disturbances and lower rates of treatment discontinuation compared to amoxicillin/clavulanic acid, along with higher patient compliance rates (95% vs 80%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of clarithromycin modified release and amoxicillin/clavulanic acid in the treatment of acute exacerbation of chronic bronchitis. Martinot, JB., Carr, WD., Cullen, S., et al.[2019]

In a study of 110 patients with mild to moderate hypertension, lisinopril showed significant reductions in office blood pressure compared to placebo, while enalapril did not demonstrate significant effects at any observation point.

Both lisinopril and enalapril were equally effective in reducing 24-hour ambulatory blood pressure, but lisinopril was more effective during the second half of the dosing interval, indicating its potential for better control of blood pressure over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension. Whelton, A., Dunne, B., Glazer, N., et al.[2013]

In a study involving 3437 patients, clarithromycin was associated with a 20% incidence of adverse events, primarily mild digestive issues, with only 1% classified as severe, indicating a generally favorable safety profile.

Clarithromycin showed fewer adverse events compared to erythromycin and other macrolides, particularly in digestive system side effects (9% vs 20%), and did not demonstrate significant toxicity to blood, liver, or kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tolerance and toxicity of clarithromycin. Wood, MJ.[2019]

In a study of 53 patients with hypersomnia, 64% reported improvement in daytime sleepiness after being treated with clarithromycin, suggesting it may be beneficial for this condition.

Objective measures of psychomotor vigilance confirmed the subjective reports of improvement, indicating that clarithromycin could enhance alertness in patients with hypersomnia linked to increased GABA-A receptor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience. Trotti, LM., Saini, P., Freeman, AA., et al.[2021]

A study involving 27 medical students demonstrated that both quinethazone and chlorothiazide are effective diuretics compared to a placebo, confirming their diuretic activity in humans.

Quinethazone showed a higher mean sodium-potassium ratio than chlorothiazide, suggesting differences in their mechanisms of action or effects on electrolyte balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the effects of chlorothiazide, quinethazone and placebo on student volunteers and on rats: a teaching exercise. Hamilton, JT., Gowdey, CW.[2018]

Two cases of hypersomnia in children were linked to therapeutic doses of clarithromycin, a side effect not previously reported, highlighting the need for awareness among clinicians.

Both cases showed that hypersomnia resolved after stopping the medication, indicating a direct relationship between clarithromycin use and the sleep disturbances observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clarithromycin-induced hypersomnia in children. Baranowski, WJ.[2019]

In a clinical trial involving 125 outpatients with acute bacterial exacerbations of chronic bronchitis, clarithromycin showed a high clinical cure rate of 96%, compared to 91% for ampicillin, indicating its efficacy as a treatment option.

While both medications had similar clinical and bacteriological response rates, clarithromycin was associated with a higher incidence of mild digestive-related adverse events (11.7%) compared to ampicillin (1.5%), suggesting a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of clarithromycin with ampicillin in the treatment of outpatients with acute bacterial exacerbation of chronic bronchitis. Aldons, PM.[2019]

In a double-blind trial involving patients with uncomplicated essential hypertension, enalapril (20 mg daily) significantly lowered both systolic and diastolic blood pressure compared to placebo, with systolic pressures at 130.5 mmHg versus 136.6 mmHg and diastolic at 82.8 mmHg versus 87.0 mmHg.

Patients taking enalapril experienced fewer spontaneous complaints and required fewer tablets per day (2.6) compared to those on placebo (4.2), indicating better tolerability and adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized evaluation of converting enzyme inhibition as the first-step treatment of mild to moderate hypertension. Sassano, P., Chatellier, G., Amiot, AM., et al.[2013]

A study involving 16 healthy volunteers found that the test tablet (Claromycin®) and the reference tablet (Klaricid®) containing 500mg clarithromycin are bioequivalent, meaning they are absorbed into the body at similar rates and extents.

The analysis showed that the confidence intervals for key pharmacokinetic measures (AUC and Cmax) fell within acceptable ranges, confirming that both formulations can be considered therapeutically equivalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Bioequivalence Study of Clarithromycin from Two Tablet Formulations after Single Oral Administration. Niopas, I., Daftsios, AC., Nikolaidis, N.[2018]

Narcolepsy type 1 is caused by the loss of hypocretin neurons, while the causes of narcolepsy type 2 and idiopathic hypersomnia are not fully understood, highlighting the need for further research into these conditions.

Current treatments for hypersomnolence, such as modafinil and sodium oxybate, are effective for many patients, but some still experience persistent sleepiness, indicating a need for new therapies like histamine H3 antagonists and GABA-A receptor modulators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central Disorders of Hypersomnolence: Focus on the Narcolepsies and Idiopathic Hypersomnia. Khan, Z., Trotti, LM.[2019]

This study identified distinct EEG patterns associated with excessive daytime sleepiness (EDS) by analyzing data from 31 individuals with high Epworth Sleepiness Scale (ESS) scores and 41 with low scores, revealing significant differences in brain wave activity.

Using machine learning algorithms, the researchers achieved an 80.2% accuracy in classifying individuals based on their ESS scores, suggesting that EEG data can provide objective biomarkers for assessing EDS, improving diagnosis and treatment tracking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Machine learning polysomnographically-derived electroencephalography biomarkers predictive of epworth sleepiness scale. Araujo, M., Ghosn, S., Wang, L., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4732573/

Clarithromycin in GABA-related Hypersomnolence No serious adverse events occurred. Interpretation. Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01146600

Clarithromycin for the Treatment of Hypersomnia Open-label use of clarithromycin in six hypersomnia patients with known (n = 4) or suspected (n = 2) excess GABAA potentiation resulted in marked improvements ...

3. ovid.com ovid.com/journals/jpsyc/pdf/10.1177/0269881113515062~improvement-in-daytime-sleepiness-with-clarithromycin-in

Improvement in daytime sleepiness with clarithromycin in ... Of these, 34 (64%) reported improvement in daytime sleepiness, while 10 (19%) did not tolerate its side effects, and nine (17%) found it tolerable but without ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04026958?term=Clarithromycin&viewType=Table&rank=9

Clarithromycin Mechanisms in Hypersomnia Syndromes In prior studies, clarithromycin resulted in significant, clinically meaningful improvements in sleepiness severity, sleepiness-related limitations in extended ...

5. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/0269881113515062

Improvement in daytime sleepiness with clarithromycin ... Of these, 34 (64%) reported improvement in daytime sleepiness, while 10 (19%) did not tolerate its side effects, and nine (17%) found it ...

6. withpower.com withpower.com/trial/phase-3-disorders-of-excessive-somnolence-8-2019-14991

Clarithromycin for Excessive Daytime Sleepiness In a study of 3437 patients, 20% reported adverse events, mostly digestive system upsets, with only 1% being severe. No significant haematological, hepatic, or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1389945724002284

Clinical considerations in the treatment of idiopathic ... Clarithromycin may improve sleepiness through negative allosteric modulation of GABAA receptors, although an ongoing study (NCT04026958) [69] aims to determine ...