Klaritromycinmekanismer ved hypersomnisyndromer
16. juli 2026 oppdatert av: Lynn Marie Trotti, Emory University
Antibiotikamedierte forbedringer i årvåkenhet: Virkningsmekanismer for klaritromycin ved hypersomnisyndromer
Hensikten med denne studien er å evaluere en medisin kalt klaritromycin for behandling av søvnighet ved to relaterte tilstander, narkolepsi uten katapleksi og idiopatisk hypersomni.
Studier har vist at klaritromycin kan redusere søvnighet, men forskerne vet ikke hvordan klaritromycin gjør dette.
Denne studien vil se på hjerneaktivitet (på magnetisk resonanstomografi [MRI] og elektroencefalogram [EEG] hjernebølger), betennelser, bakterier som lever i tarmen og cerebrospinalvæske, for bedre å forstå hvordan klaritromycin kan redusere søvnighet.
Denne studien vil rekruttere 92 deltakere som vil bli randomisert til å motta klaritromycin eller placebo i 14 dager.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Detaljert beskrivelse
Overdreven søvnighet på dagtid og lang søvntid er vanlige trekk ved mange nevrologiske lidelser, inkludert myotonisk dystrofi, Parkinsons sykdom og hypersomnisyndromer i sentralnervesystemet. Disse sistnevnte syndromene er en gruppe lidelser med overlappende kliniske fenotyper og, bortsett fra når det gjelder narkolepsi på grunn av hypokretinmangel (narkolepsi type 1), potensielt delt patofysiologi.
Patologisk søvnighet på dagtid ved disse lidelsene svekker yrkesmessig ytelse, begrenser livskvaliteten og mer enn dobler risikoen for motorkjøretøy og annen ulykke. Fordi den underliggende årsaken til de fleste av disse hypersomnisyndromene ikke er kjent, er behandlinger rettet mot å øke monoaminerg signalering involvert i våkneforfremmelse. Likevel kan minst en fjerdedel av pasienter med hypersomnisyndrom ikke oppnå tilfredsstillende kontroll over symptomene med disse behandlingene, og funksjonshemming eller medisinske permisjoner er ofte nødvendig. Det er et klart behov for nye behandlinger for overdreven søvnighet på dagtid for å løse denne svikten i dagens standard for omsorg.
I tidligere studier resulterte klaritromycin i signifikante, klinisk meningsfulle forbedringer i alvorlighetsgraden av søvnighet, søvnighetsrelaterte begrensninger i utvidede daglige aktiviteter og søvnighetsrelatert livskvalitet. Lang søvnvarighet og søvntreghet, begge tilleggssymptomer på hypersomniforstyrrelser som bidrar til funksjonssvikt, ble også forbedret med klaritromycin.
Hypotese: Klaritromycin vil redusere overdreven søvnighet og andre symptomer på hypersomniforstyrrelser, målt ved selvrapportering og objektiv testing.
Mål 1: Å identifisere sentralnervesystemets mediatorer av klaritromycins evne til å fremme våkenhet og redusere søvnighet, blant pasienter med sentrale hypersomnisyndromer.
Hypotese 1a: Endringer i cerebrospinalvæske (CSF) forsterkning av gamma-aminosmørsyre-A (GABA-A) reseptorfunksjon in vitro vil være assosiert med forbedringer i selvrapportert og objektivt målt søvnighet.
Hypotese 1b: Endringer i funksjonell tilkobling vil være assosiert med forbedringer i selvrapportert og objektivt målt søvnighet.
Mål 2: Å undersøke ekstra-nevronale mekanismer som klaritromycin kan redusere søvnighet, inkludert endringer i systemisk betennelse og endringer i gastrointestinal mikrobiota sammensetning, hos pasienter med sentrale hypersomnisyndromer.
Hypotese 2a: Forbedring av søvnighet ved bruk av klaritromycin vil være positivt assosiert med reduksjoner i systemisk inflammasjon, spesielt reduksjoner i nivåer av tumornekrosefaktor-alfa (TNFα).
Hypotese 2b: Forbedring av søvnighet ved bruk av klaritromycin vil være positivt korrelert med modulering av gastrointestinal dysbiose.
Studietype
Intervensjonell
Registrering (Faktiske)
83
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Georgia
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Atlanta, Georgia, Forente stater, 30329
- Emory Sleep Center
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 60 år (Voksen)
Tar imot friske frivillige
Nei
Beskrivelse
Inklusjonskriterier:
- diagnose av idiopatisk hypersomni eller narkolepsi type 2
- alder 18-60
- fri for våknefremmende medisiner, søvnig til tross for gjeldende våknefremmende medisiner, eller villig til å seponere gjeldende våknefremmende medisiner i minst 5 halveringstider før baseline-tiltak
- fri for pre- eller probiotiske kosttilskudd i minst seks måneder før baseline-tiltak
Ekskluderingskriterier:
- andre potensielle årsaker til hypersomnolens, inkludert moderat eller alvorlig søvnapné, alvorlig periodisk bevegelsesforstyrrelse i lemmer med opphisselse, ukontrollerte metabolske forstyrrelser, hypokretinmangel eller katapleksi
- kontraindikasjon for klaritromycin
- kontraindikasjon til noen av studieprosedyrene
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Klaritromycin
Deltakere i denne studiegruppen vil motta klaritromycin i 14 dager.
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Klaritromycin vil doseres som 500 mg to ganger daglig, én gang ved oppvåkning og én gang med lunsj, i 14 dager.
Andre navn:
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Placebo komparator: Placebo
Deltakere i denne studiegruppen vil motta en placebo som matcher klaritromycin i 14 dager.
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En placebo for å matche klaritromycin vil doseres som 500 mg to ganger daglig, én gang ved oppvåkning og én gang med lunsj, i 14 dager.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change in Epworth Sleepiness Scale (ESS) Score
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Maintenance of Wakefulness Test (MWT) for Sleep Latency
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Gamma-aminobutyric Acid Receptor A (GABA-A) Potentiation
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Default Mode Network (DMN) Connectivity
Tidsramme: Day -2, Day 13
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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.
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Day -2, Day 13
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Change in Tumor Necrosis Factor - Alpha (TNF-α)
Tidsramme: 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.
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Day -1, Day 14
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Change in Gastrointestinal Microbiome Composition
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
On-Treatment Sleep Duration
Tidsramme: Day 1 through Day 14
|
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.
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Day 1 through Day 14
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Change in Fatigue Severity Scale (FSS) Score
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Multidimensional Fatigue Inventory (MFI-20) Score
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Sleep Inertia Questionnaire (SIQ) Score
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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On-Treatment Sleep Inertia Likert Scale
Tidsramme: Day 1 through Day 14
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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.
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Day 1 through Day 14
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Change in Interleukin 1 Alpha (IL-1α)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interleukin 1 Beta (IL-1β)
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Interleukin 2 (IL-2)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interleukin 6 (IL-6)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interleukin (IL-8)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interleukin (IL-15)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interleukin (IL-18)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
|
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Change in Tumor Necrosis Factor Beta (TNF-β)
Tidsramme: Day -1, Day 14
|
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.
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Day -1, Day 14
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Change in Interferon Alpha (INF-α2a)
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Functional Outcomes of Sleep Questionnaire (FOSQ) Score
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in Hypersomnia Severity Index (HSI)
Tidsramme: Day -1, Day 14
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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.
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Day -1, Day 14
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Change in MRI Functional Connectivity
Tidsramme: Day -2, Day 13
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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.
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Day -2, Day 13
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Change in MRI Task Performance - N-Back Accuracy
Tidsramme: Day -2, Day 13
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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.
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Day -2, Day 13
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Change in MRI Task Performance - N-Back Reaction Time
Tidsramme: Day -2, Day 13
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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.
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Day -2, Day 13
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Lynn Marie Trotti, MD, MSc, Emory University
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
4. september 2019
Primær fullføring (Faktiske)
18. juni 2025
Studiet fullført (Faktiske)
18. juni 2025
Datoer for studieregistrering
Først innsendt
17. juli 2019
Først innsendt som oppfylte QC-kriteriene
18. juli 2019
Først lagt ut (Faktiske)
19. juli 2019
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
7. august 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
16. juli 2026
Sist bekreftet
1. juli 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- IRB00108681
- 1R01NS111280 (U.S. NIH-stipend/kontrakt)
- 2025P011204 (Annen identifikator: Emory IRB)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
Etter avidentifikasjon vil individuelle pasientdata samlet inn under utprøvingen som ligger til grunn for resultatene rapportert i artikkelen, være tilgjengelig for å deles med andre forskere.
IPD-delingstidsramme
Data vil være tilgjengelig for deling fra og med 3 måneder etter artikkelpublisering og slutt 3 år etter artikkelpublisering.
Det vil bli gjort rimelige forsøk på å imøtekomme forespørsler etter 3 år.
Tilgangskriterier for IPD-deling
Individuelle deltakerdata vil være tilgjengelige for deling med forskere som gir et metodisk forsvarlig forslag, og med andre enheter som gir en klar begrunnelse for databruk.
Data vil bli delt for analyser for å nå målene med det godkjente forslaget.
Forslag til bruk av dataene skal rettes til lbecke2@emory.edu.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .