Narcolepsy Without CataplexyPhase 2NCT04026958
Clarithromycin Mechanisms in Hypersomnia Syndromes
A Phase 2 study testing Clarithromycin in people with Narcolepsy Without Cataplexy and Idiopathic Hypersomnia, run by Emory University at 1 site in United States.
Trial summary
The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in narcolepsy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Narcolepsy Without Cataplexy, Idiopathic Hypersomnia, Narcolepsy With Cataplexy
- What is being tested?
- Clarithromycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2019to 18 Jun 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- diagnosis of idiopathic hypersomnia or narcolepsy
- age 18-60
- free of wake-promoting medication, sleepy despite current wake-promoting medications, or willing to discontinue current wake-promoting medication for at least 5 half-lives prior to baseline measures
Who cannot join
- other potential causes of hypersomnolence, including untreated moderate or severe sleep apnea, severe periodic limb movement disorder with arousals, uncontrolled metabolic disorders
- contraindication to clarithromycin
- contraindication to any of the study procedures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Antibiotic-mediated Improvements in Vigilance: Mechanisms of Action of Clarithromycin in Hypersomnia Syndromes
The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in narcolepsy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. This study will look at brain activity (on magnetic resonance imaging [MRI]), inflammation, bacteria living in the gut, and cerebrospinal fluid, to better understand how clarithromycin can reduce sleepiness. This study will recruit 92 participants who will be randomized to receive clarithromycin or a placebo for 14 days.
Read the detailed description
Excessive daytime sleepiness and long sleep durations are common features of many neurologic disorders, including myotonic dystrophy, Parkinson's disease, and the central nervous system hypersomnia syndromes.
Pathologic daytime sleepiness in the central nervous system hypersomnia disorders impairs occupational performance, limits quality of life, and more than doubles motor vehicle and other accident risk. Because the underlying cause of the majority of these hypersomnia syndromes is not known, treatments are aimed at increasing monoaminergic signaling involved in wake promotion. Yet, at least one-fourth of patients with hypersomnia syndromes cannot achieve satisfactory control of symptoms with these treatments and disability or medical leaves of absence are often necessary. There is a clear need for novel treatments for excessive daytime sleepiness to resolve this failure of the current standard of care.
In prior studies, clarithromycin resulted in significant, clinically meaningful improvements in sleepiness severity, sleepiness-related limitations in extended activities of daily living, and sleepiness-related quality of life. Long sleep durations and sleep inertia, both ancillary symptoms of hypersomnia disorders that contribute to functional impairments, were also improved with clarithromycin.
Hypothesis: Clarithromycin will reduce excessive sleepiness and other symptoms of hypersomnia disorders, as measured by self-report and objective testing.
Aim 1: To identify central nervous system mediators of clarithromycin's ability to promote wakefulness and reduce sleepiness, among patients with central hypersomnia syndromes.
Hypothesis 1a: Changes in cerebrospinal fluid (CSF) enhancement of gamma-aminobutyric acid-A (GABA-A) receptor function in vitro will be associated with improvements in self-reported and objectively measured sleepiness.
Hypothesis 1b: Changes in functional connectivity will be associated with improvements in self-reported and objectively measured sleepiness.
Aim 2: To probe extra-neuronal mechanisms by which clarithromycin may reduce sleepiness, including changes in systemic inflammation and changes in gastrointestinal microbiota composition, in patients with central hypersomnia syndromes.
Hypothesis 2a: Improvement in sleepiness with clarithromycin use will be positively associated with reductions in systemic inflammation, especially reductions in levels of tumor necrosis factor-alpha (TNFα).
Hypothesis 2b: Improvement in sleepiness with clarithromycin use will be positively correlated with modulation of gastrointestinal dysbiosis.
- Being tested
- Clarithromycin, Placebo
- Keywords
- Neurology
- Medical subject headings
- Idiopathic Hypersomnia, Narcolepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClarithromycinDrug
Also called Biaxin
Clarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days.
PlaceboDrug
A placebo to match clarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Clarithromycin | Experimental | Participants in this study arm will receive clarithromycin for 14 days. Receives: Drug: Clarithromycin |
| Placebo | Placebo comparator | Participants in this study arm will receive a placebo to match clarithromycin for 14 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Epworth Sleepiness Scale (ESS) Score
The Epworth Sleepiness Scale asks participants to respond to 8 scenarios with how likely they are to fall asleep on a 4-point scale where 0 = "would never doze" and 3 = "high chance of dozing". Total scores range from 0 to 24 where higher scores indicate a higher chance of falling asleep during daytime activities. The change in ESS score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 mean that the mean score at Day 14 was lower than the mean score at Baseline, indicating less sleepiness.
Measured: Day -1, Day 14
Change in Maintenance of Wakefulness Test (MWT) for Sleep Latency
The MWT polysomnographic procedure for sleep latency examines how well participants stay awake during several trials where participants relax in a quiet room for 40 minutes. One study found the mean sleep latency among persons without a sleep disorder to be 35.2 minutes. The change from baseline is calculated as baseline sleep latency minus sleep latency at Day 14, in minutes. Positive values result when the duration of sleep latency at Day 14 is lower than at Baseline.
Measured: Day -1, Day 14
Change in Gamma-aminobutyric Acid Receptor A (GABA-A) Potentiation
Cerebrospinal fluid (CSF) is drawn to determine the change in levels of GABA-A potentiation between the study arms. The difference between measured current with GABA alone and the current measured with GABA + CSF yields a measure of potentiation for each CSF sample in each condition. The change from baseline is calculated as the baseline value minus the value at Day 14.
Measured: Day -1, Day 14
Change in Default Mode Network (DMN) Connectivity
The default mode network (DMN) consists of a group of highly correlated brain regions most active during quiet rest, while the task positive network (TPN) is the brain network activated for goal-directed tasks. DMN connectivity changes with sleep states and it is increasingly implicated in the symptomatology of sleepiness. During resting state, sleep deprived participants demonstrate reduced static connectivity with the DMN. Changes in DMN between the Baseline 1 (Day - 2) and Day 13 visits are compared between treatment groups, particularly using quasi-periodic patterns (QPPs), which interrogate network-level connectivity on a dynamic scale. Preservation of the temporal dimension provides more insight into how this spatiotemporal network propagates across condition and pathology. The DMN/TPN QPP correlation is reported.
Measured: Day -2, Day 13
Change in Tumor Necrosis Factor - Alpha (TNF-α)
Blood samples are used to determine the change in levels of TNF-α between the study arms. TNF-α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.
Measured: Day -1, Day 14
Change in Gastrointestinal Microbiome Composition
Changes in microbiome composition, as measured by alpha diversity using the Shannon Index, via 16S ribosomal ribonucleic acid (rRNA) sequencing results are compared between study arms. The Shannon Index measures both abundance and evenness of microbial species, values of 0 indicate that a community has only one species. The higher the value the higher the diversity of species in a particular community. Change from baseline is calculated by subtracting the Day 14 value from the value at Baseline. Numbers greater than 0 indicate that the Day 14 Shannon index value is lower than at Baseline.
Measured: Day -1, Day 14
Secondary outcomes (19)
On-Treatment Sleep Duration
Participants log when they go to bed and when they wake up in order to calculate the number of minutes spent sleeping. The average duration of sleep across 14 days is compared between study arms.
Measured: Day 1 through Day 14
Change in Fatigue Severity Scale (FSS) Score
Fatigue severity is measured with the Fatigue Severity Scale (FSS). The FSS is a 9-item instrument where responses are on a scale of 1 to 7 where 1 = "disagree" and 7 = "agree". Total scores range from 9 to 63 where higher scores indicate greater fatigue. The change in FSS score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating decreased fatigue.
Measured: Day -1, Day 14
Change in Multidimensional Fatigue Inventory (MFI-20) Score
The MFI-20 is a 20-item instrument assessing fatigue severity. Responses are on a 5-point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Positively phrased items are reverse scored so that the total score ranges from 20 to 100 where higher scores indicate greater severity of fatigue. The change in MFI-20 score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating decreased fatigue.
Measured: Day -1, Day 14
Change in Sleep Inertia Questionnaire (SIQ) Score
The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. Total scores range from 21 to 105 and higher scores indicate increased difficulty from tiredness. The change in SIQ score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating reduced difficulty awakening.
Measured: Day -1, Day 14
On-Treatment Sleep Inertia Likert Scale
Sleep inertia is measured with a single item on a 10-point Likert scale asking participants how difficult it was for them to wake up in the morning, where 1 = "not difficult at all" and 10 = "very difficult". The average scores across 14 days are compared between study arms.
Measured: Day 1 through Day 14
Change in Interleukin 1 Alpha (IL-1α)
Blood samples are used to determine the change in levels of IL-1α between the study arms. IL-1α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-1α is obtained by subtracting the IL-1α level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin 1 Beta (IL-1β)
Blood samples are used to determine the change in levels of IL-1β between the study arms. IL-1β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-1β is obtained by subtracting the IL-1β level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin 2 (IL-2)
Blood samples are used to determine the change in levels of IL-2 between the study arms. IL-2 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-2 is obtained by subtracting the IL-2 level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin 6 (IL-6)
Blood samples are used to determine the change in levels of IL-6 between the study arms. IL-6 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-6 is obtained by subtracting the IL-6 level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin (IL-8)
Blood samples are used to determine the change in levels of IL-8 between the study arms. IL-8 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-8 is obtained by subtracting the IL-8 level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin (IL-15)
Blood samples are used to determine the change in levels of IL-15 between the study arms. IL-15 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-15 is obtained by subtracting the IL-15 level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interleukin (IL-18)
Blood samples are used to determine the change in levels of IL-18 between the study arms. IL-18 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-18 is obtained by subtracting the IL-18 level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Tumor Necrosis Factor Beta (TNF-β)
Blood samples are used to determine the change in levels of TNF-β between the study arms. TNF-β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in TNF-β is obtained by subtracting the TNF-β level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Interferon Alpha (INF-α2a)
Blood samples are used to determine the change in levels of INF-α2a between the study arms. INF-α2a is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in INF-α2a is obtained by subtracting the INF-α2a level at Day 14 from the Baseline level.
Measured: Day -1, Day 14
Change in Functional Outcomes of Sleep Questionnaire (FOSQ) Score
The FOSQ is a 30-item instrument assessing how sleepiness impacts daily activities. There are five subscales assessing General Productivity, Activity Level, Vigilance, Social Outcomes, and Intimate and Sexual Relationships. Items are scored on a 4-point scale where 1 = extreme difficulty and 4 = no difficulty. Subscale scores are obtained by calculating the mean score for the items in that subscale and each can range from 1 to 4, where higher scores indicate less difficulty due to sleepiness. A total score is obtained by calculating the means of the subscale scores and multiplying that by the number of subscales with a score. The total score ranges from 5 to 20 and higher scores indicate less difficulty from sleepiness. The change in FOSQ score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores below 0 signify that the mean score at Day 14 was higher than the mean score at Baseline, indicating reduced difficulty from sleepiness.
Measured: Day -1, Day 14
Change in Hypersomnia Severity Index (HSI)
The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia. The change from baseline is calculated as the baseline score minus the score at Day 14. The change in HSI score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating reduced severity of hypersomnia symptoms.
Measured: Day -1, Day 14
Change in MRI Functional Connectivity
For functional connectivity analyses, each functional scan is parceled into the 246 regions of interest (ROIs), spanning Yeo's 7 networks contained in the Brainnetome Atlas and mean timecourse is calculated for each group. Pearson correlations between each pair of ROIs are calculated, to determine the strength of functional connectivity between each pair of regions and inter/intra-network. This yields a functional connectivity matrix for each functional scan (at both a subject- and group-level). These correlation matrices are Fischer z-transformed and averaged across each condition to create a mean functional connectivity matrix for each condition. Here, the average default mode network (DMN) connectivity is reported. Z-scores have a mean of 0 and scores higher than 0 indicate increased functional connectivity. The change from Baseline is calculated by subtracting the Day 13 score from the score at Day -2. Values lower than 0 mean that the Day 13 score was higher than at baseline.
Measured: Day -2, Day 13
Change in MRI Task Performance - N-Back Accuracy
Participants complete a working memory task during functional magnetic resonance imaging (fMRI). The change in task performance is measured as accuracy during 3 different levels of back tasks (0-back, 1-back, and 2-back), from baseline to on-treatment (Day 13). The 0-back test has participants respond to a prespecified stimulus and is a control condition. The 1-back involves remembering and responding to a prior stimulus, while a stimulus two trials earlier is responded to with the 2-back. The change in the percentage of correct responses is obtained by subtracting the percentage at Day 14 from the Baseline percentage. Values below 0 signify that the mean percent accuracy at Day 14 was higher than the mean percent accuracy at Baseline, indicating increased accuracy.
Measured: Day -2, Day 13
Change in MRI Task Performance - N-Back Reaction Time
Participants complete a working memory task during functional magnetic resonance imaging (fMRI). he change in task performance is measured as reaction time during 3 different levels of back tasks (0-back, 1-back, and 2-back), from baseline to on-treatment (Day 13). The 0-back test has participants respond to a prespecified stimulus and is a control condition. The 1-back involves remembering and responding to a prior stimulus, while a stimulus two trials earlier is responded to with the 2-back. The change in the reaction time of responses is obtained by subtracting the time at Day 14 from the Baseline time. Scores above 0 signify that the mean time at Day 14 was lower than the mean time at Baseline, indicating faster reaction time.
Measured: Day -2, Day 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start4 Sep 2019
- Primary completion18 Jun 2025
- Study completion18 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Narcolepsy Without CataplexyStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lynn Marie Trotti, Emory University
- Investigators
- Lynn Marie Trotti, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04026958
- Sponsor's protocol ID
- IRB00108681
- Other IDs
- 1R01NS111280, 2025P011204
- Status last verified
- Jul 2026
- First submitted
- 17 Jul 2019
- Last updated
- 7 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After de-identification, individual patient data collected during the trial that underlie the results reported in the article will be available to be shared with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antibiotic-mediated Improvements in Vigilance: Mechanisms of Action of Clarithromycin in Hypersomnia Syndromes
- ClinicalTrials.gov ID
- NCT04026958
- Acronym / sponsor ID
- IRB00108681
- Keywords
- Neurology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 18 Jun 2025 (actual)
- Study completion
- 18 Jun 2025 (actual)
- First posted
- 19 Jul 2019 (actual)
- Results
- Posted 7 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in narcolepsy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. This study will look at brain activity (on magnetic resonance imaging [MRI]), inflammation, bacteria living in the gut, and cerebrospinal fluid, to better understand how clarithromycin can reduce sleepiness. This study will recruit 92 participants who will be randomized to receive clarithromycin or a placebo for 14 days.
Detailed description
Excessive daytime sleepiness and long sleep durations are common features of many neurologic disorders, including myotonic dystrophy, Parkinson's disease, and the central nervous system hypersomnia syndromes.
Pathologic daytime sleepiness in the central nervous system hypersomnia disorders impairs occupational performance, limits quality of life, and more than doubles motor vehicle and other accident risk. Because the underlying cause of the majority of these hypersomnia syndromes is not known, treatments are aimed at increasing monoaminergic signaling involved in wake promotion. Yet, at least one-fourth of patients with hypersomnia syndromes cannot achieve satisfactory control of symptoms with these treatments and disability or medical leaves of absence are often necessary. There is a clear need for novel treatments for excessive daytime sleepiness to resolve this failure of the current standard of care.
In prior studies, clarithromycin resulted in significant, clinically meaningful improvements in sleepiness severity, sleepiness-related limitations in extended activities of daily living, and sleepiness-related quality of life. Long sleep durations and sleep inertia, both ancillary symptoms of hypersomnia disorders that contribute to functional impairments, were also improved with clarithromycin.
Hypothesis: Clarithromycin will reduce excessive sleepiness and other symptoms of hypersomnia disorders, as measured by self-report and objective testing.
Aim 1: To identify central nervous system mediators of clarithromycin's ability to promote wakefulness and reduce sleepiness, among patients with central hypersomnia syndromes.
Hypothesis 1a: Changes in cerebrospinal fluid (CSF) enhancement of gamma-aminobutyric acid-A (GABA-A) receptor function in vitro will be associated with improvements in self-reported and objectively measured sleepiness.
Hypothesis 1b: Changes in functional connectivity will be associated with improvements in self-reported and objectively measured sleepiness.
Aim 2: To probe extra-neuronal mechanisms by which clarithromycin may reduce sleepiness, including changes in systemic inflammation and changes in gastrointestinal microbiota composition, in patients with central hypersomnia syndromes.
Hypothesis 2a: Improvement in sleepiness with clarithromycin use will be positively associated with reductions in systemic inflammation, especially reductions in levels of tumor necrosis factor-alpha (TNFα).
Hypothesis 2b: Improvement in sleepiness with clarithromycin use will be positively correlated with modulation of gastrointestinal dysbiosis.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clarithromycin | Experimental | Drug: ClarithromycinParticipants in this study arm will receive clarithromycin for 14 days. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants in this study arm will receive a placebo to match clarithromycin for 14 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- diagnosis of idiopathic hypersomnia or narcolepsy
- age 18-60
- free of wake-promoting medication, sleepy despite current wake-promoting medications, or willing to discontinue current wake-promoting medication for at least 5 half-lives prior to baseline measures
Key exclusion criteria (3 listed)
- other potential causes of hypersomnolence, including untreated moderate or severe sleep apnea, severe periodic limb movement disorder with arousals, uncontrolled metabolic disorders
- contraindication to clarithromycin
- contraindication to any of the study procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClarithromycinAlso: BiaxinClarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days. | Drug | Clarithromycin |
| PlaceboA placebo to match clarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days. | Drug | Placebo |
Primary outcome
Change in Epworth Sleepiness Scale (ESS) Score
Time frame: Day -1, Day 14
The Epworth Sleepiness Scale asks participants to respond to 8 scenarios with how likely they are to fall asleep on a 4-point scale where 0 = "would never doze" and 3 = "high chance of dozing". Total scores range from 0 to 24 where higher scores indicate a higher chance of falling asleep during daytime activities. The change in ESS score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 mean that the mean score at Day 14 was lower than the mean score at Baseline, indicating less sleepiness.
Change in Maintenance of Wakefulness Test (MWT) for Sleep Latency
Time frame: Day -1, Day 14
The MWT polysomnographic procedure for sleep latency examines how well participants stay awake during several trials where participants relax in a quiet room for 40 minutes. One study found the mean sleep latency among persons without a sleep disorder to be 35.2 minutes. The change from baseline is calculated as baseline sleep latency minus sleep latency at Day 14, in minutes. Positive values result when the duration of sleep latency at Day 14 is lower than at Baseline.
Change in Gamma-aminobutyric Acid Receptor A (GABA-A) Potentiation
Time frame: Day -1, Day 14
Cerebrospinal fluid (CSF) is drawn to determine the change in levels of GABA-A potentiation between the study arms. The difference between measured current with GABA alone and the current measured with GABA + CSF yields a measure of potentiation for each CSF sample in each condition. The change from baseline is calculated as the baseline value minus the value at Day 14.
Change in Default Mode Network (DMN) Connectivity
Time frame: Day -2, Day 13
The default mode network (DMN) consists of a group of highly correlated brain regions most active during quiet rest, while the task positive network (TPN) is the brain network activated for goal-directed tasks. DMN connectivity changes with sleep states and it is increasingly implicated in the symptomatology of sleepiness. During resting state, sleep deprived participants demonstrate reduced static connectivity with the DMN. Changes in DMN between the Baseline 1 (Day - 2) and Day 13 visits are compared between treatment groups, particularly using quasi-periodic patterns (QPPs), which interrogate network-level connectivity on a dynamic scale. Preservation of the temporal dimension provides more insight into how this spatiotemporal network propagates across condition and pathology. The DMN/TPN QPP correlation is reported.
Change in Tumor Necrosis Factor - Alpha (TNF-α)
Time frame: Day -1, Day 14
Blood samples are used to determine the change in levels of TNF-α between the study arms. TNF-α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.
Change in Gastrointestinal Microbiome Composition
Time frame: Day -1, Day 14
Changes in microbiome composition, as measured by alpha diversity using the Shannon Index, via 16S ribosomal ribonucleic acid (rRNA) sequencing results are compared between study arms. The Shannon Index measures both abundance and evenness of microbial species, values of 0 indicate that a community has only one species. The higher the value the higher the diversity of species in a particular community. Change from baseline is calculated by subtracting the Day 14 value from the value at Baseline. Numbers greater than 0 indicate that the Day 14 Shannon index value is lower than at Baseline.
19 secondary outcomes
On-Treatment Sleep Duration
Time frame: Day 1 through Day 14
Change in Fatigue Severity Scale (FSS) Score
Time frame: Day -1, Day 14
Change in Multidimensional Fatigue Inventory (MFI-20) Score
Time frame: Day -1, Day 14
Change in Sleep Inertia Questionnaire (SIQ) Score
Time frame: Day -1, Day 14
On-Treatment Sleep Inertia Likert Scale
Time frame: Day 1 through Day 14
Change in Interleukin 1 Alpha (IL-1α)
Time frame: Day -1, Day 14
Change in Interleukin 1 Beta (IL-1β)
Time frame: Day -1, Day 14
Change in Interleukin 2 (IL-2)
Time frame: Day -1, Day 14
Change in Interleukin 6 (IL-6)
Time frame: Day -1, Day 14
Change in Interleukin (IL-8)
Time frame: Day -1, Day 14
Change in Interleukin (IL-15)
Time frame: Day -1, Day 14
Change in Interleukin (IL-18)
Time frame: Day -1, Day 14
Change in Tumor Necrosis Factor Beta (TNF-β)
Time frame: Day -1, Day 14
Change in Interferon Alpha (INF-α2a)
Time frame: Day -1, Day 14
Change in Functional Outcomes of Sleep Questionnaire (FOSQ) Score
Time frame: Day -1, Day 14
Change in Hypersomnia Severity Index (HSI)
Time frame: Day -1, Day 14
Change in MRI Functional Connectivity
Time frame: Day -2, Day 13
Change in MRI Task Performance - N-Back Accuracy
Time frame: Day -2, Day 13
Change in MRI Task Performance - N-Back Reaction Time
Time frame: Day -2, Day 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. After de-identification, individual patient data collected during the trial that underlie the results reported in the article will be available to be shared with other researchers.
Related trials for Narcolepsy Without Cataplexy
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
A Study of TAK-360 in Adults With Narcolepsy Without Cataplexy (NT2)
Narcolepsy Type 2
RecruitingPhase 3
A Phase 3 Study to Evaluate the Efficacy and Safety of Samelisant in Patients With Narcolepsy (AWAKE)
Narcolepsy
Recruiting
Decreasing Nightmares in Adults With Narcolepsy
Narcolepsy, Narcolepsy Type 1
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynn Marie Trotti, MD, MSc principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clarithromycin in people with Narcolepsy Without Cataplexy and Idiopathic Hypersomnia, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Epworth Sleepiness Scale (ESS) Score (time frame: Day -1, Day 14). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.