Clarithromycin for Excessive Daytime Sleepiness

Overseen By Tyler Blake

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

92 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing clarithromycin, an antibiotic, to see if it can help people with narcolepsy and idiopathic hypersomnia who struggle with excessive sleepiness. Researchers will study how it affects brain signals, body inflammation, and gut bacteria. Clarithromycin has shown potential in improving sleepiness in previous trials.

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.

What data supports the idea that the drug Clarithromycin for Excessive Daytime Sleepiness is an effective treatment?

The available research shows that Clarithromycin may help reduce excessive daytime sleepiness in some patients. In a study, 64% of patients reported feeling less sleepy during the day after taking Clarithromycin. Additionally, those who felt better also showed improved alertness in tests. However, 19% of patients couldn't handle the side effects, and 17% didn't notice any improvement. This suggests that while Clarithromycin can be effective for some, it doesn't work for everyone and can have side effects. ^{1 2 3 4 5}

What safety data is available for clarithromycin in treating excessive daytime sleepiness?

Clarithromycin has been associated with adverse events in various studies. In a study of 3437 patients, 20% reported adverse events, mostly digestive system upsets, with only 1% being severe. No significant haematological, hepatic, or renal toxicity was reported. In children, clarithromycin has been linked to hypersomnia, which resolved after stopping the drug. Comparisons with other antibiotics showed similar side effects, but clarithromycin had fewer digestive issues than erythromycin. Overall, clarithromycin is generally well-tolerated, but hypersomnia and digestive disturbances are potential side effects. ^{6 7 8 9 10}

Is Clarithromycin a promising drug for treating excessive daytime sleepiness?

The provided research articles do not contain information about Clarithromycin or its effects on excessive daytime sleepiness, so we cannot determine if it is a promising drug for this condition based on the given data. ^{11 12 13 14 15}

Research Team

Lynn Marie Trotti, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

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]

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]

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]

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 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]

References

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

Central Disorders of Hypersomnolence: Focus on the Narcolepsies and Idiopathic Hypersomnia. [2019]

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

Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience. [2021]

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

Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial. [2018]

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

Daytime sleepiness and sleep habits of Australian workers. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Machine learning polysomnographically-derived electroencephalography biomarkers predictive of epworth sleepiness scale. [2023]

6. United States 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. [2019]

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

Clarithromycin-induced hypersomnia in children. [2019]

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

The tolerance and toxicity of clarithromycin. [2019]

9. England pubmed.ncbi.nlm.nih.gov

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

10. New Zealand pubmed.ncbi.nlm.nih.gov

Human Bioequivalence Study of Clarithromycin from Two Tablet Formulations after Single Oral Administration. [2018]

11. Canada pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

A double-blind randomized evaluation of converting enzyme inhibition as the first-step treatment of mild to moderate hypertension. [2013]

13. England 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. [2013]

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

Differential effects of a missed dose of trandolapril and enalapril on blood pressure control in hypertensive patients. [2019]

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

Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril. [2019]